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THE HEALT- ~ T--11 all aE.'sQu E"K -4 CILEJ ~~ 0 ~~`~~~i~ 2'0a WOMEN a report of the Surgeon General THIS REPORT CONTAINS SOM E TECHNICAL ERRORS. AN ERRATA SHEET TO FOLLOW SHORTLY r4: s U.S. DEPARTMENT OF HEALTH. EDUCATION, AND WELrARE Public Health Service Office of the Assistant Secretary for Health Office on Smoking and Health . TIMN 0048200

TNE sECRETART OF NEAITN, EOUCATION,ANO WEIFARE WA3N 1 N OTON, O. C. 20201 The Honorable Thomas P. O'Neill,Jr. Speaker of the House of Representatives Washington, D.C. 20515 Dear Mr. Speaker: I hereby submit the 12th annual report that the Department of Health, Education, and Welfare (DHEW) has ;pr,epared for Congress as required by the Public Health Cigarette Smoking Act of 1969, Public Law 91-222, and its predecessor, the Federal Cigarette Labeling and Advertising Act. This report is one of the most alarming in the series. It clearly establishes that women smokers face the same risks as men smokers of lung cancer, heart disease, lung disease and other consequences. Perhaps more disheartenieYg is the harm which mothers' smoking causes to their unborn babies and infants. The report is not all bad news. It presents recent data showing that women are turning away from smoking in response to the warnings of government, voluntary agencies and physicians. The precipitate rise in women's deaths from lung cancer and chronic lung disease demand that this trend away from cigarettes be accelerated. our scientists expect that by 1983, the lung cancer death rate will exceed that of any other type of cancer among women. Citizens of our free society may decide for themselves whether to smoke cigarettes. The health consequences of this decision make it imperative for their government to assure that the decision is an informed one. This series of reports is one way in which DHEW is striving to meet this critical responsibility. /J s Patricia Roberts Harris s TIMN 0048201

PREFACE This report is more than a factual review of the health consequences of s?noking for women. It is a document which challenges our society and, in particular, our medical and public health communities. This report points out that the first signs of an epidemic of s,noking-related disease among wornen are now appearing. Because women's cigarette use did not become widespread until the onset of World War II, those women with the greatest intensity of smoking are now only in their thirties, forties, and fifties. As these women grow older, and continue to smoke, their burden of smoking-related disease will grow larger. Cigarette smoking now contributes to one- fifth of the newly diagnosed cases of cancer and one-quarter of all cancer deaths among women--more cancer and more cancer deaths among women than can be attributed to any other known agent. Within three years, the lung cancer death rate is expected to surpass that for breast cancer. A similar epidemic of chronic obstructive lung disease among women has also begun. , Four main themes e -nerge from this report to guide future public health efforts. First, women are not immune to the dama.-ing effects of smoking already documented for men. The apparently lower susceptibility • to smoking related diseases among women smokers is an illusion reflecting the fact that women lagged one-quarter century behind men in their widespread use of cigarettes. Second, cigarette smoking is a major threat to the outcome of pregnancy and well-being of the newborn baby. Third, women may not start smoking, continue to smoke, quit smoking, or fail to quit smoking for precisely the same reasons as men. Unless future research clarifies these differences, we will find it difficult to prevent initiation or to promote cessation of cigarette smoking among .vomen. Fourth, the reduction of cigarette smoking is the keystone in our nation's long term strategy to promote a healthy lifestyle for wo;,en and men of all races and ethnic groups. i 4 TIMN 0048202 `

THE FALLACY OF WOMENIS IMMUNITY All of the major prospec.'ive studies of smoking and mortality have reached consistent conclusions. Death rates from coronary heart disease, cironic lung disease, lung cancer, and • overal l mortality rates a,e significantly increased among both women and men smoker--,. . These risks increase with the , amount smoked, duration of smoking, depth of inhalation, and the "tar" and nicotine- delivery of the cigarette smoked. In these studies, condacted during the past three decades, relative mortality risks among female, smokers appeared to be less than those of male smokers. It is now clear, however, that these studies were comparing the death rates of a generation oti established, lifelong male smokers with a, generation of women who had not yet taken up smoking with full intensity.. Ev-_.n, 'those older women who reported smoking a large, number of cigarettes per day had not smoked cigarettes in the. . sarne WLy as their male counterparts. Now that the cigarette smoking characteristics of women.and men are becoming increasingly similar., their relative. risks of smoking-relited illness w.ll become. increasingiy, similar. This fallacy of w.)men's apparent immunity. is clearly il lustrated ,by differences in the .timing of. :the growth i1 , lung cancer among men and women in this ;'century. . Lung= cancer deaths among males began to increase during the 1930.s,. as those men who had conve •ted from other. forms of tobacco to cigarette smoking before- the_.turn of the century gradually :accuniulated decades of . inhaled -tobacco, exposure. : By the time of ..the first retros~iective studies of smoking"`and lung cancer in .1950, two ent ire generations. of . men had already become lifelong cigarett=: smokers. Relatively few -women from these generations siroked cigarettes, .and even fewer had smoked cigarettes. since their -adolescence. Those young wornen who had taken up smoking intensively during, World War .11 were..onty 'in their twenties and thirties. In 1950, women accounted' r for less than one n in twelve. deaths from lung cancer. Thereafter, the aae* adjusted lung cancer death rate among women accelerated, and the male predominance in lung cancer declined. Lung cancerr surpassed uterine cervical cancer as a cause of d-;ath in women. By 1968, as the findings of many large population . prospective studies were being published, women accounted for one.-sixth of all lung - cancer •deaths. These ;studies found that women cigarette smokers had 2.5 to. 5 Vnes greater death rates from lung ® - -----y--~

cancer than wo-nen nonsmokers. By 1979, women accounted for fully one-fourth of all lung cancer deaths. Over the next few years, women cigarette smokers' risk of lung cancer death will approach 8 to 12 thnes that of women nonsmokers, the same relative risk as that of inen. Lung cancer has four main histological types: epider.noid, small cell, adenocarcinoma, and large cell carcinoma. As several studies have shown, the incidence of each of these types of lung cancer displays a clear relationship to cigarette smoking among both men and women. Epider!noid and small cell lung cancer appear to be more prominent among men, while adenocarcinoma of the lung now appears to be more prominent among women. The recent acceleration of lung cancer incidence among women has in fact been more rapid than the corresponding growth of lung cancer among men in the 1930s. Again, this difference in the initial rate of acceleration of lung cancer incidence does not refute the demonstrated causal relation between cioarette smoking and lung cancer among both sexes. Instead, differences in the rate of increase of lung cancer incidence may reflect changes in the carcinogenic properties of cigarette smoke, the style of cigarette smoking, or the interaction of cigarette smoking with other environmental hazards. It is noteworthy that those men who died of lung cancer in the 1930s came from a -eneration that had gradually ` converted to cigarettes from other, non-inhaled forms of tobacco. By contrast, the first regular tobacco users amono wo:nen were almost exclusively cigarette smokers. The 1979 Report on Smoking and Health documented nu:merous instances where cigarette smoking adds to ' the hazards of the workplace environment among men. Among, women, this report reveals two such occupational exposures-- asbestos and cotton dust--which have been clearly demonstrated to interact with cigarette smoking. The fact that evidence is limited among women does not imply that wonen are protected from the dangerous interactions of smoking and occupational exposures. PREGNANCY, INFANT HEALTH, AND REPRODUCTION Scientific studies encompassing various races and ethnic groups, cultures and countries, involving hundreds of thousands of pregnancies, have shown that cigarette smoking during pregnancy significantly affects the unborn fetus and the i i i . TIMN 0048204

the newborn baby. - These damaging effects have been repeatedly shown to operar,e independently of all other factors which influence the outco.ne of pregnancy. The effects are increased by heavier smocing and are reduced if a woman stops smoking during preg;:aney. • Numerous toxic substances- in cigarette smoke, such as nicotine and hydrogen cyanide, cross the placenta to affect the fetus directly. The ca_rbon monoxide from cigarette smoke is transported into the fetal blood, and deprives the growing. baby of oxygen. Fetal growth is directly retarded. The resulting reduction in retal weight and size has many unfortunate- consequences. Women who smoke cigarettes during piegnancy have more spontaneous abortions, and a greater incidence of bleeding during pregnancy, premature and prolonged rupture of amniotic membranes, abruptio -placentae and • placenta previa. W_,men who smoke cigarettes during pregnancy have. more `etal and neonatal deaths- than nonsmoking pregnani wom-;n. A relation between maternal smoking. and Sudden Infa it Death Syndrome • has now been estabiished...:.... The". direct''-harmful effects of smoking on the fetus have"long. term • consequences. Children - of mothers who smoked during pregnancy lag 'measurably In physical growth; there. • may~ also be : ef Pects on " behavior and"cognitive development. The oextent )f these deficiencies increases with the number of. cigarettes smoked.'' - "The damaging".effe.-ts 'of '.maternal smok.ing on infants are not restricted to preg.ancy: _ -Nicotine; a known poison,. is found in- the breast milk of smoking mothers. Children whose parents smoke cigarettes have more respiratory infections and more hospitalizations• in th3 first year of life. Women' who smoke cigarettes - have more than three times the risk of, dyino of ' stroke due to subarachnoid hemorrhage, and as much as two times the risk of dying of heart • attack in comparison • to nonsmoking women. 7he use of oral contraceptives in addition to smoking; however,• causes a markedly increased risk, iicluding a 22-fold increase, in the risk of subarachnoid heinorrhagic stroke and -, a 20-fold increase in heart attack in heavy smokers. WHY DO WOMEN SMOKE? Cigarette consumption in this country is now declining. Annual per capita consu:np;ion has decreased from 4,258 in

1965 to an estimated 3,900 in 1979. From 1965 to 1979, the proportion of adult male cigarette smokers declined from 51 to 37 percent. idot only have millions of men quit 00 ai' smoking, but the rate of initiation of smoking among adolescent males has now slowed. Frofn 1965 to 1976, the proportion of adult women cigarette smokers remained virtually unchanged at 32 to 33 percent. Since 1976, however, the proportion of adult rvornen cigarette smokers appears to have declined to 28 percent. Although adult woraen are now beginning to quit smoking at rates comparab,le to' adult men, the rate of initiation of smoking among younger women has not declined. This report documents numerous differences by sex in the perceived - role of cigarette smoking, in attitudes toward health and lifestyle, and in methods of coping with stress, anger, and boredom. Yet the significance of these differences, and their relation to differences in smoking patterns, remains poorly understood. Although it is frequently observed that women in or,o,anized smoking cessation programs have more severe withdrawal symptoms and lower rates of successful quitting than men, these observations have not been systematically confirmed for the general population. In the past, women pted to quit or succeeded in quitting s:noking may have atte,n less frequently than rnen. The recent decline in the propor- tion of women smokers, however, suggests that women's attempted and successful quitting rates have now increased. Although weight vain is a frequently cited consequence of quitting smoking, the association of weight gain with cessation of smoking has not been the subject of sufficient scrutiny. Controlled studies with careful measurement on representative populations of women do not exist. The impact of the fear of weight gain after quitting has not been ade- quately examined. If weight gain does result from cessation of smoking, its exact mechanism must be determined. Even more problernatic are marked differences by sex in the distribution of smoking prevalence by occupation. Men with advanced education and professional occupations have taken the lead in quitting smoking, but wo:nen in administrative and managerial positions have relatively high smoking prevalence rates. Although 20 percent or fewer male physicians smoke, the proportions of cigarette smokers among women health professionals, especially nurses and psychologists, remain disturbingly high. Recent changes in smoking prevalence among black V TIMN 0048206

women and men have p-iralleled those of the general population. From 1965 to 1979, the proportion of black women cigarette smokers -ieclined• from 34 to 29 percent, while the proportion of black men smokers declined from 61 to* 42_•percent. ._ However, differences by race in the onset, maintenance, and cessation of smoking have not been adequately °•explored. Little is known about cigarette smoking among other ethnic and min•)rity groups. ADOLESCENT SMOK1 NG •' ' The' health "consequences oi' 's;noking evolve - over a lifetime. Evidence continues to accuwulate, for example, that cigarette smoking_produces measurab e lung changes' even in childhood ind-young-aduithood. Youn g cigarette smokers •of bottr sexes show more evidence 'of small 'airway dysfunction, and a higher prevalence of cough, wheezing, • phlegm production, and other '•respiratory^ symptoms. Th-: health damage due to cigarette smoking increases when an individual -beg•ins regular smoking earlier in life. Yet, as this report documents, the average age of onset of regul ir smoking among '-women ' has, continuously declined durin_; the last '50 years,'"and continues to• decline. ' " According to a recestt survey by the National Institute :of Education, cigarette smoking among adolescent girls now -exceeds that among adolescent boys: In the 17-19 year' age group, there are almost 5--emale cigarette smokers for every 4"male • cigarette smokers. • The causes of this inversion are far from clear. 1ille do -not' yet• understand the signal events in *the initiation of smok ing among young women. It is possible that parents set e=ampies concerning lifestyle, health attitude, and risk-taking much earlier in childhood. The beginning of• junior high -;chool or entrance into the work force may be equally critical events. We do not know enough about an adolescent's sens_ of competence and self-mastery, and how these roles differ among women and men. Although smoking patterns among girls correlate with parental, peer and sibling smoking habits, educational level, type of school curriculum, academic performance, socioeconomic ' status, and other forms of substance 2buse, the practical significance of these empirical correlations is unclear. vi --.--~ ® i--~~ -- .,~.__ ._._._.._... ->. ;...~= ~... ® ® - _~-~-~-~ .............. r..:_.._._.._ -

VJON1EN AND THE CHANGING CIGA;ZETfE As this report docu:nents, the proportion of men and women smokers using brands with lowered "tar" and nicotine continues to grow. Adolescents of both sexes have followed this trend, to the point where nonfilter cigarettes are relatively rare among young adults. Although the preponderance of scientific evidence continues to suggest that cigarettes with lower "tar" and nicotine are less hazardous, four serious warnings are in order. First, the reported "tar" and nicotine deliveries of cigarettes are standardized machine measure;nents. They do not necessarily represent the smoker's actual intake of these substances. Evidence is now ~nounting that individuals who switch to cioarettes with lowered "tar" and nicotine •inhale more deeply, smoke a great,er proportion of their cigarettes, and in some cases smoke more cigarettes. Second, "tar" and nicotine are not the only dangerous chemical components of ci`arette smoke. Many conventional filter cigarettes, in fact, may deliver -nore carbon monoxide than nonfilter cigarettes. Third, it has not been established that lower "tar" and nicotine cioarettes have less harmful effects on the unborn fetus and•baby; on women and men at high risk for developing - coronary heart disease, such as those with elevated cholesterol or high blood pressure; or on workers with adverse occupational exposures. It has not been established that switching to a lower "tar" and nicotine cigarette has any salutory effect on individuals who already have smoE;ircgm- related illnesses, such as coronary heart disease, chronic ' bronchitis, and emphysema. Fourth, even the lowest yield cigarettes present health hazards for both women and men that are very much higher d than smoking no cigarettes at all. The single most effective way for both women and men smokers to reduce the hazards associated with cigarettes is to quit smoking. As this report demonstrates, little is known about the effects of these product changes on the initiation, maintenance and cessation of smoking, particularly among women. It has not been determined whether the availability of cigarettes with lowered "tar" and nicotine has made it easier for young women to experiment with and beconne addicted to cigarettes. It is not known whether smokers of vii TIMN 0048208

the iowest yield cigarettes are more or less likaly to attempt ~ to..--qut,, or to- succe-sd in, quitting, than smokers of conventional filtertip or nonfilter cigarettes. The extent to which the act of switch ing to a lower 11tar" cigarette may serve as a substitute fo r quitting may differ among women and men. PUBLIC HEALTH RESPONSIBILITIES This report, which includ=;s data compiled by individuals from both-- ,ins%de and outside the Government, has confirmed in every_ wa.y the judge:nent of the World Health Organization, that there can no longer be any doubt among informed people that cigarette smoking is a major and removable cause of ill health and "premature death. Each individual woman must make her own decision about this significant health issue. Secretary Harris has noted that, the role of the Government, and , all responsible health professionals, Is ':o assure that this decision is an Informed one. In issuin_; this report, we hope to help the public health community' a.:complish this purpose. Julius. B. Richmond, M.D. Assistant Secretary for •. Health and Surgeon Gener1l

ACicNOwLEDGEMENTS This report was prepared by agencies of the U.S. Department of Health, Education and Welfare under the general editorship of the Office on Smoking and i-iealth, f ohn IM. Pinney, Director. Consulting scientific editors were David M. Burns, Assistant Clinical Professor, Pulmonary Division, University of California at San Diego, San Diego, California and John H. Holbrook, M.D., Assistant Professor of Internal Medicine, University of Utah Medical School, Salt Lake City, Utah. ' Introduction and Summary Office on Smoking and Health Patterns of Cigarette Smoking Office on Smoking and Health Jeffrey E. Harris, M.D., Ph.D., Assistant Professor, Department of Economics, Masasachusetts Institute of Technology, Cambridge, Massachusetts; Clinical Assoeiate, Medical Services, Massachusetts General Hospital, Boston, Massachusetts. Overall Mortality National Heart, Lung, and Blood Institute Eugene. Rogot, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, 'vlaryland; Thomas J. Thom, Division of Heart and Vascular Diseases, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland Morbidity National Center for Health Statistics Ronald W. Wilson, M.A., Chief, Health Status and Demographic Analysis Branch, Division of Analysis, + National Center for Health Statistics, Hyattsville, Maryland. Cardiovascular Diseases National Heart, Lung, and Blood Institute. G.C. McMil/an, M.D., Ph.D., Associate Director for Etiology of Arteriosclerosis and Hypertension, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute, National Institutes of t-lealth, Bethesda, Maryland. xi 210 r.UIMN 004

Cancer National Cancer Institute ~ ~ Jesse L. Steinfeld, M.D., Dean, Medical College of Virginia, Richmond, Vi rginia. Non-Neoplastic Broncilopulmonary niseases •National Heart, Lung, and Rlood Institute Richard A.. ' Pordow, M.D., Associate Research Physiologist, 'Univers4iy of California at San nPeRo, San Diego•, 'California;-•Claude J'.M: Lenfant, M.D., Director, Divisiort of Lunj Disease, National Heart, Lung, 'and' Riood Institute, National Institutes of Health, gethesda; Maryland • Barbara Marzetta Liv, Division of Lung Disease, National Heart, Lung, 'and Rlood (nstitute, I nstitutes of ' Health, [? ethesda; 'Maryiand National Eric R. Jurrus, Division "of Lung- Disease, National : Heart, Lung,•• and Bloo i Institute, National - Institutes of ` Health, Bethesda, M;ryiand. . irttei'action ' Between Smoking and nccupatiortal • . Exposures '. -s - , •` National •Institute •of O-:cupational Safety and Health + jeanrte= •Steelman, = Ph:D., American 'Health = Foundation, •New York,, New° York ° Steven D. Stellman, Chief, Division' of Health & Toxicology, ° American 'Nealth ' 'Foundatiort, •New •York, `4New'~'ork' : . ' ' Pregnancy •. and Infant H-;alth• '' ' . 'NYtionai`. Institute of Child Development•:' :` Health and • Human Eileen G. Hasselmey-sr, Ph.D., R.N., Associate 'birector - for ~ Scientific'• Review, National Institute of °`- Child ' Health ` •and` •, H.iman ' Development, • National '1•nstitutes of Health, •Re-,hesda 'Maryland. • Mary '~:Meyer, .' Associate Professor of Epidemio'logy; ' Johns - Hapkins University °School of Hygiene and Public Heal th, Paltimore, Maryland. - Lawrence D. Longo, M.D=, Professor of Physiology and '-nbstertrics and' Gynecology,- •Loma ~Linda University School of Medicine, Lom i Linda, California - . • Donaid R. +• Mattison, ` M.D., • Senior Investigator, Pregnancy : Research Pranch, National Institute of Child • Health• and'. Human- Development, National %' 1 nstitutes of Health, Betilesda, Maryland. dictL}14 VtAI'''Ji1VL

Peptic Ulcer National Institute of Arthritis, Metabolism and Digestive Diseases Travis E. Solomon, M.D., Ph.D., Center for Ulcer Research and Education, VA Wadsworth Medical Center and UCLA School of Medicine, Los Angeles, California Janet Elashoff, Ph.D., Center for Ulcer Research and Education, VA Wadsworth Medical Center and UCLA School of Medicine, Los Angeles, California. Interactions of Smoking with Drugs, Food Constituents and Responses to Diagnostic Tests Cheryl Fossum Graham; Division of Drug Experience, Office of Biomet•rics and Epidemiology, Bureau of Drugs, Food and Drug Administration. Psychosocial and Rehavioral Aspects of Smoking in Women Initiation, Maintenance, and Cessation Ellen R. Gritz; Ph.D., Research Psychologist, Veterans Administration Medical Center, Rrentwood, California and Associate Research Psychologist, Department of Psychiatry and Fehavioral Sciences, School of Medicine, University of California, Los Angeles, California. Ann 'Frunswick, Ph.t?., Senior Research Associate . (Sociomedical Sciences), Center for Sociocultural Research on Drug Use, School of Public Health, Columbia University, New York, New York. Karen L. Bierman, M.A., C?epartment of Psychology, University of California, Los Angeles, California. The editors acknowledge with gratitude the many distinguished' scientists, physicians, and others who assisted in the preparation of this report by coor- dinatinfg manuscript preparation, contributing criti- cal reviews of the manuscripts or helping in other ways. Elvin A. Adams, M.D., M.P.H., Practicing Internal Medicine, Fort Worth, Texas. Josephine D. Arasteh, Ph.D., Health Scientist Administrator, Human Learning and Behavior Rranch, Center for Research for Mothers and Children, National Institute of Child Health and Human . TIMN 0048212

Development, National Institutes of Health, Rethesda, M aryiand. Lester Breslow, M.D., M.P.H., Dean, School of Public Health, University of California at Los Angeles, Los Angeles, California. A. Sonia Buist, M.D., Associate Professor of Medicine & Physiology, University of Oregon Health Sciences Center, Portland, Oregon. David M. Rurns, M.D., Assistant Clinical Professor, Pulmonary Division, University of California at San , Delgo, San Diego California. Thomas C. Chalmers, M.D., President and Dean, Mount Sinai Medical Center, New York, New York. ' Florence L. Denmark, Ph.D., Professor of Psychology, i Ph.D. Programs in Psychology, City University of New f York, New York, New York.._ Robert M. Donaldson, Jr., M.D., Chief, Medical Services, Westhaven Veterans Hopitai, Westhaven, Connecticut. ", Joseph T. Doyle, M.D., Professor of Medicine and Head, Division of Cardiology of the Department of Medicine, Albany Medical College of Union University, Albany, New York. Elizabeth M. Earley, Ph.D., Chief, Section of Cytogenetics, Division of Pathology, Rureau of Biologies, Food and Drug Administration, F?ockvilie, Maryland. f Bernard H. Ellis, Jr., Program Director for Smoking ; and Occupational Activities, Office of Cancer al Natio er t Natio l Ca stit te i ti ~' C nc n , n ommun ca ons, na u i nstitutes of Health, Bethesda, Maryland. Diane Fink, M.D., Associate Director, Medical Applications of Cancer Research and Coordinator, Smoking, Cancer, and Health Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Harold E. Fox, M.D., Associate Professor of Clinical ; Obstetrics and Gynecology, Deoartment of Obstetrics and Gynecology, Columbia Presbyterian Medical Center, and Medical Director, Western and Upper Manhattan Perinatal Network, New York, New York. Joseph H. Gainer, D.V.M., Veterinary Medical Office, Division of Veterinary Medical Research, Bureau of Veterinary Medicine, Food and Drug Administration, ; Rockville, Maryland. xiv T7MN 0048213

Stanley N. rershoff, Ph.n., Director, `!utrition Institute and rhairman, rraduate nepartment of Nutrition, Tufts University, ~Aedford, Massachusetts. Sharon 'A. Hall, Ph.!?., Assistant °rofesscr, University of California at San Francisco, Lanaley Porter Neuropsychiatric Institute, San Francisco, California. Jane Halpern, M.n., ASPER, Office of Health and Disability, United States Department of Labor, Washington, D.C. Reatrix A. Hamburg, Research Psychiatrist, Laboratory of Development Psychology, National lnstitute of Mental Health, National Institutes of Health, Rethesda, Maryland. Virginia G. Harris, M.D., Director, Maternal and Child Health, Onondago County Health Department, Syracuse, New York. John H. Holbrook, tiA.D., Assistant Professor of Internal Medicine, University of Utah `"edicat School, Salt Lake City, Utah. , Stanley James, M.D., Professor of Pediatrics, Obstetrics, and Gynecology, College of physicians and Surgeons, Columbia Preshyterian Medical Center, New York, New York. Hershel Jick, M.n., noston Collaborative Drug Surveil-lance Program, Boston University PRedical Center, Waltham, Massachusetts. Reese T. Jones, "".n., Professor . of Psychiatry, Department of Psychiatry, University of California at San Francisco, Langley Porter Neuropsychiatric Institute, 'San Francisco, California. Philip Kimbel, -~".1?., Head, Pulmonary niseases Section, Albert Einstein ft4edical Center, Philadelphia, Pennsylvania. Jan '0/. Kuzma, Ph.ll., Chairman and Professor of Biostatistics, Department of Riostatistics and Epidemiology, Loma Linda University, Loma Linda, California. Abraham Lilienfeld, M.D., M.P.H., O.Sc.,University Distinguished Service Professor, Jot+ns Hopkins School of Hygiene and Public Health, Raltimore t1aryiand. Harold A. Menkes, M.D., Associate Professor of P4edicine, Department of Medicine, Johns Hopkins University, Raltimore, Maryland. Kenneth A"oser, M.D., Professor of Medicine and xv ,_ - ,.~ AQ,7.14

Director, Pulmonaiy Division, University of California, San Diego, California. Mariquita:AFMuilan, N-itional Institute of Occupational Safety and Health, R)ckvil le, Maryland. Janyce E. Notopoulo-;, Program Analyst, Office of Planning and Eval iation, National Institute of Child Health and Human f•)evelopment, National 1 nstitutes of Health, Bethesda, Maryland. Albert Oberman, M.D., . Director, Division of Preventive Medicine, School of Medicine, University of Alabama,. Rirminghim, Alabama. Ralph S. Paffenberger, Jr., M.D., Professor of Epidemiology, Depa,•tment o.f Health Services, California State Health Department, Berkeley California. . Richard Peto, - M_0., Radeliff Clinic, Oxford University, Oxford, E,rgland. Malcolm C. Pike, PFi.D., Professor, Community and Family Medicine, S-:hool of Medicine, University of Southern California at Los Angeles, Los Angeles, California. . Ovidt R. Pomerleau, Ph.D., Professor of Psychology and Ps.yohiatry,. Univ-rrsity of Connecticut School of Medicine, Farmington, Connecticut. Phi!! H. Price, M_r),, Chief, Metabolic Products Branch, Division of Ruminant Species, Bureau of Veterinary Medicine, Food and nrux Administration, Rockville, Maryland. Mrs. Dorothy Pechman Rice, Director, National Center for Health •Statisti•;s, Office of the Assistant Secretary for, Health. Hyattsvile, Maryland. Anthony Robbins; M-i i., Director, National Institute of Occupational Safety and Health, Center for nisease Control, Rockvil le, Ma -yland. - . Harold P. Roth, M.D,$ Associate Director for Digestive Diseases & Nutrition; National Institute of Arthritis, Metabolis,ti, and Digestive Diseases, National Institutes of Health, Bethesda, *Maryland. Philip Sapir, Special Assistant to the Director for Behavioral and Socia l Sciences -and Chief, Human Learning and Pehavior-ii Branch, Center for -Research for Mothers and Children, National Institute of Child Health and Human Devetopment, National Institutes of Health, Bethesda, Maryiand. Marvin A. Schnieder.ma-i, Ph.D., Associate Director for ,.~._,.,._~....~.a.., : ~ .u.•.: .;-.--..- . ........ T _ ~., ~

Scieoce Policy, National Cancer Institute, National Insti[utes of Health, Pethesda, k'arviand. I rvin;t J. Setikoff, M.D., Professor, Mount Sinai Merli,.at Center, New York, New York. S. i. Shihko, Ph.D., Chief, Contaminants and Natural Toxicants Pranch, Division •of Toxicology, Rureau of Foods, Food and Rrug Administration, P.ockville, Maryl=.nd. Jeremiah Stamler, Chairman, Department of Community Health and Preventive Medicine, ' Northestern Univer-;ity Medical School, ChicaAo, Illinois. Jesse Steinfeld, M.D., Dean, Medical College of Virgini:t, Richmond, Virginia John ,. Vanderveen, Ph.D., Director, Division of Nutrition, Rureau of Foods, Food and nrug Administration, Rockvitle, Maryland. Eve W= inhlatt, Assistant Director, Department of Researc7t and Statistics, Health Insurance Plan of Creater New York, New York, New York. Samuel S. C. Yen, Rl.n., Professor and Chairman, DepartmOnt of Reproductive Medicine, University of [:alifcrnia, San Diego, LaJolta, California. The editors also acknowledge the heiE, of the following staff who among others assisted in the preparation of the reoort. John L. pagrosky, Acting Associate Director for Program Operations, Office on Smoking and Health, Rockviile, Maryland. Jacauetine 0. Rlandford, Clerk-Typist, Office on Smoking and Health, Rockville, Maryland. Petty Rud,,, Secretary (TypinP), Office on Smoking and Health, Rockvilie, Marvland. John F. Hardesty, Jr., Public information Officer, Office on Smoking and Nealtb, Rockville, Marvtand Patricia E. Healy, Clerk (Typing), Office on Smoking and t-iealth, Rockvilie, Maryland. Douglas T. Howard, Jr., Ph.D., Senior Editor, Koba A ssociates, Washington, D.C. Robert S. Hutchings, Associate Director for i nformation and Program t,evelopment, Office on Smoking and Health, Rockville, Maryland. Margaret E. :Cetterman, Secretary (Typing), Office on Smoking and aeatth, Rockville, Maryland. xvii 4

Richard A. Lasco, Ph.D., Rureau of Health, Education, nter for_,,,Disease. Control, Atlanta, Georgia. Ce, Frances Lazerow, Vice-President, Koba Associates, Washington, D.C. Joanne Luoto, M.D., M.P.H. Medical Office, Office on Smoking and Health, Rockville, Maryland. Jack R. Maples, Senior Research Associate, Koba Associates, Washington, D.C. _ Marianne R. McCarthy, Pt+.Ll., Director of Technical Support Services, Koha Associates, Washington, D.C. Marjorie L. Olson, Secretary (Stenography), •Office on Smoking and Health, Rockville, Maryland. Keiley __L.,_Phillips, M.D., AR.P.H., Expert Consultant, Office on Smoking and Health, Rockville, Mayland. David L. Pitts, Public Health Advisor, Operations Praneh, Nutrition Division, Rureau of Smallpox Eradication, Center for nisease Control, Atlanta, Georgia. Donald R. Shopland, Technical Information Officer, Office on Smoking and Health, Rockville, Maryland. Linda R. Spiegeiman, Administration Assistant, Office on ,°moking and Health, Rockville, Maryland. Carol M. Sussman, Technical Publication Writer/Editor, Office on Smoking and Health, Rockville, Maryland. Ronald G. Thomas, Public Health Analyst, Office on Smoking and Health, Rockville, Maryland. Selwyn M. WainRrow, Public Health Analyst, Office an Smoking and Health, Rockville, Maryland. Ann E. Wessel, Public Health Analyst, Office on Smoking and Health, Rockville, Maryland. Carole L. Winn, Assistant Chief, Clinical Chemistry Standardization Section, Clinical Chemistry Division, Metabolic Plochemistry Rranch, Pureau of Laboratories, Center for Disease Control, Atlanta, Georg ia. TIMN 0048217

CONTJVTS INTRODUCTION AND SIAtAARY ............................t PART I .x . PATTERNS OF SMDK I NG AMCNG W+CMEN AND MEN I N THE UNITED STATES, 1900 - 1979 ....................1S The Rise of Cigarette Smoking: 1900-1950 ......................17 The Emergence of Filtertip Cigarettes: 1951-1963......... 24 Increasing Public Health Awareness: 1964-1979..........25 Exposure to Cigarette Smoke Among Successive Birth Cohorts .........................31 Cigarette Smoking Asnong Women...37 Sunmary ......................... PART II BIOh1EDICAL ASPECTS OF SMOKING OVERALL MORTALITY ...........................53 Mortality Trends.......................53 Epidemiological Studies ................5$ American Cancer Society 25 - State Study ....................58 Swedish Study ...................60 Canadian Veterans Study......... 60 Japanese Study of 29 Health Districts ......................60 British Doctors Study...........61 Framingham Heart Study..........61 British - Norwegian Migrant Study ..........................62 Overall Mortality For Females-Cigarette Smokers versus Non-Smokers............ 63 Mortality Ratios ................63 Amount Smoked and Age........... 63 Duration of Smoking .............72 i r r xix t TIMN 0048218

., / , N®N®NEOPLAST I C BRONCPiOPUI.ArtCNARY D I SEASES ........... 160 Definitions .......................•....160 Smoking and Respiratory "Aortaiity...... 161 Smoking and the Epidemiology and Pathology of Chronic Obstructive Lung Disease ............................... 166 Smoking and Respiratory PAorbidity...... 173 Smoking and Pulmonary Function.........182 Smoking and nEarly" Functional Abnormalities ..................183 Smoking and Ventilatory Function .......................187 INTERACTION BETWEEN SMOKING AND OCCUPATIONAL EXPOSURES .........................................203 P REGNANC."Y Smoking Patterns in tii/omen ..............204 Patterns of a•nployment.................208 The Reproductive Role ..................213 Specific Interactions Between Occupational Exposure'and Smoking.....215 Asbestos ........................215 Cotton Dust .....................218 AM INFANT HEALTH ........................224 Smoking, Birth Weight, and Fetal Growth ................................224 Placental Ratios ................226 Gestation and Fetal Growth......229 Long Term Growth and Development ................................230 Role of Maternal Weight Gain....237 Smoking Fetal and Infant Mbrtal ity and Morbidity .............................243 Spontaneous Abortion............ 243 Congenital Malformations........ 245 Perinatal Mortality .............250 ; Cause of Death................... 252 Complications of Pregnancy and Labor...254 Preeclamsia .....................256 Preterm Delivery, Pregnancy Complications and Perinatal Mortality by Gestation........ 258 Long Term Morbidity and Mortality...... 263 Sudden Infant Death Syndrome....266 xxi TIMN 0048220

Long Term''iorbidity and Nortality...... 263 Sudden Infant Death Syndrome....266 Vtechanisms ............................. 267 Experimental Studies ................... 270 Tobacco smoke ................... 270 Nicotine ........................270 Carbon monoxide .................272 Polycyclic aromatic hydrocarbons ...... ...........................275 Other components ................276 Fertility ..............................277 Smoking and Reproduction in Women ..........................277 Smoking and Age of Menopause....278 Smoking and Reproduction in Men ................................278 Fertilization and Conceptus Transport ......................279 PEPTIC tJLGER ................... 297 INTERACTIONS OF SMOKING WITH DRUGS, FaOD CCNSTITtJENTS AND RESPONSES TO DIAGNOSIC TESTS..... 302 Women Smokers and Nonsmokers and Drug Consumption Patterns ..................302 Aitered Clinical Response to Drug Therapy by Smokers Compared to Nonsmokers...............•.•..••.....•304 :; Oral Contraceptives and Smoking........306 Alterations in Normal Clinical Laboratory Values In Women Smokers....308 The Influence of Smoking on the Nutritional Needs of Women............309 PART lII BEHAVIORAL ASPECTS OF SMOKING................... •.. PSYCHDSOCIAL AND BEHAVIORAL ASPECTS OF SMOKING IN WOMEN: INITIATION, MAINTENANCE, AND CESSATION....318 Initiation of Smoking in Adolescent Giris .................................318 ,r1MN 0048221,

_........r, , v , .,uv I cDI.Glj 1. ucIt ar Iv# ...............................319 Prevalence and Patterns of Adolescent Cigarette Use ....... 320 Prevalence ..................... 321 Age of initiation in smoking ........................ 323 Number of cigarettes smoked ..... 326 Type of cigarette smoked ........ 326 Smoking Cessation ...............328 Smoking prevalence and ethnicity ...............................328 Alcohol and marijuana use....... 329 Demographic and Psychosocial Correlates of Smoking in Adolescence ............. 329 Socioeconomic influences ........ 329 Family patterns ................. 330 Smoking among parents and siblings ....................... 330 Peer group infiuence............ 332 Scholastic achievement and aspirations .................... 334 Dynamic/Personality factors ..... 334 Predicti'ons of future smoking behavior ....................... 336 Prevention of Smoking and Considera- tions for Future Research ............. 338 Prevention of the initiation of smoking ........................ 338 Research goals .................. 339 Maintenance of Smoking ................. 340 Smoking l3ehavior ................ 340 Patterns of cigarette smoking ................... 340 Smoking prevalence and ethnicity .................345 Pharmacological Effects of Smoking ........................345 Nicotine ................... 347 Peripheral effects....347 Central effects....... 347 A possible role for nico- tine in smoking mainte- nance ..................... 347 Differences in nicotine metaboiism................. 350 4 TIMN 0048222

.jinwKing and Stimulation Effects ...............................350 Smoktng Cessatio~ ....................352 Demographics.......................... 354 Age .............,....................354 Education ............................355 income...............................355 Occupation...........................355 Psychology of Changing Smoking Habits ....................................355 Treatment Studies.................... 356 The,Smoking Withd,awal Syndrome...... 364 Treatment Fiecom,ne,idat i ons,............365 Conclusion ....... :....... ............. 367 Dissemination of Information About .Smoking .............................367 Health Attitudes and Behaviors ...............................367 Sources of tnformation......s...368 Health c-tre providers......368 Educator-,.......... ........ .37t} Peer gro~ip.....,............371 Family......- ...............371 : Media...'...................371 .Advertising ................372 The failure•to disseminate information ...............373 Smoking aad weight control ........ .................373 Stress at Work_.... .............375 Smoking Habits of Health Professionals,,,,,, Physicians......... ...378 Psychsiogists......... 381 Nur.se;..... ........... 381 The Pregnant Smoker • A Special . Target........................... 385 Sources of info~mation.........,385 Physician Advic=...... .,.,,,,...387 Prevalence of Si-,oking and Quitting during Pregnancy......392 Psychosocial Factors in Quitting • ®

INTRODUCTION AND SUMMARY INTRnDUCTION The 1980 Report on the Health Consequences of Smoking focuses upon the evidence relating cigarette smoking to health effects in women. It is not presented as a detailed discussion of the entire range of effects of smoking on heaith. Such a detailed review of all existing evidence can be found in the 1979 Report of the Surgeon General on Smoking and Health. Instead, this volume on smoking and women's health is offered as a review and reappraisal of smoking and major health relationships specifically in women. It is intended to serve the medical community as a unified source of existing scientific evidence about health effects of smoking cigarettes for women. As an examination of current knowledge, it will logically lend itself to application in both the personal and public health arenas. its content is the work of numerous scientists within the Department of Health, Education, and Welfare, as well as scientific experts outside that organization. This volume examines the major issues relating tobacco use to women's health including trends in consumption, the biomedical evidence of the health effects of cigarette usage by women, and determinants of smoking initiation, maintenance; and cessation. This section summarizes the principal findings of this report. It is hoped that the entire volume will serve to highlight the established risks of smoking for women and their children, as well as to define the areas in need of further investigation. SUMMARY PATTERNS OF CIGARETTE SMOKING 0 1. Women have differed from men in their historical onset of widespread cigarette use, in the rate of diffusion of smoking among each new birth cohort, in their intensity of cigarette smoking and their use of various types of cigarettes. 2. Men took up cigarette smoking rapidly at the beginning of the twentieth century, especially during World War I. Cigarettes rapidly replaced other forms of tobacco. I . TIMN 0048224

and men current smokers has increased. The relationship of, this finding to recent deciines in the average F.T.C. "tarn and nicotine deliveries of cigarettes is not well understood. 10. With each successive generation, the smoking characteristics of women and men have become increasingly simifar. 11. Among women, the average age of onset of regular smoking progressively declined with each successive birth cohort--from 35 years of age for those born before 1900, to 16 years of age among those born 1951 to 1960. The average age of onset of regular smoking among young women is now virtually identical to that of young men. 12. Maximum smoking prevalence rates have declined substantially in recent birth cohorts of men. Men born 1,931 to 1940 reached a peak smoking proportion of 61 percent during 1960-62, while men born 1941 to 1950 reached a peak smoking proportion of 58 percent in 1958-69. PRen born 1951 to 1960 reached a peak smoking proportion of 40 percent in 1976. Among recent cohorts of women, peak smoking prevalence rates have declined to a much smaller extent. Women born 1931 to 1940 reached a peak smoking proportion of 45 percent in 1966-68, while women horn 1941 to 1950 reached a peak smoking proportion of 41 percent in 1970-73. Women born 1951 to 1960 reached a peak smoking proportion of 38 percent in 1976. Among the generation born 1951 to 1960, the proportions of women and men smoking ' :igarettes are now virtually identical. 13. The proportions of women and men smokers in each ?ge group have declined. Among those born before 1951, this decline in smoking prevalence resulted mainly from smoking e--ssation. Ry contrast, the observed decline in smoking ps'evatence among younger men born 1951 to 1960 has resulted from both smoking cessation and a lower rate of smoking initiation. This decline in the rate of onset of smoking among young men has not been observed for young women. 14. Recent survey data on adolescent smoking habits rev'al that by ages 17 to 19, smoking prevalence among wowen exceeds that of men. This finding supports the con•'iusion that the rate of initiation of smoking among young men --but not that of young women--is declining. The future ciga.•ette use of the youngest generations of women is uncer- tain. 15. With each successive birth cohort, the accumulated years of cigarette smoking per woman has progressively appro-tched the accumulated years of cigarette smoking per 3 0 10 i T~N 0048226

W man. Each successive birth cohort has also experienced progessively smaller sex differences in the fraction of lifetime years of smoking that represents filtertip cigarett& use. 16. Among men born during this century, each sueces.sive` birth cohort has thus far experienced fewer cumulative years of cigarette smoking, higher proportionate exposure to filtertip cigarettes, and lower smoking prevalence rates. This relationship between birth date and cigarette smoke exposure does not hold for women. Women born 1921 to 1940 have experienced suhstantialiy higher smoking prevalence rates that earlier generations. Unless they cult smoking in substantial numbers, these women, currently aged 40 to 59, will surpass older women in total years of cigarette smoking per capita, the total years of nonfilter cigarette smoking per capita, and in the total number of cigarettes smoked. The healthconsequences of this enhanced exposure to cigarette smoke among women are likely to be more prominent in the coming decades. MORTALITY 1. The mortaiity ratio for women who smoke cigarettes is about 1.2 or 1.3 compared to nonsmokers. 2. Mortality ratios for women increase with the ys amount smoked. In the largest prospective study the mortality ratio was 1.63 for the two-pack-a-day smoker as compared to nonsmokers. 3. Mortaiity ratios are generally proportional to the duration of cigarette smoking; the longer a woman smokes, the greater the excess risk of dying. 4. Mortality ratios tend to be higher for those women who begin smoking at a young age compared to those who begin smoking later. 5. Mortality ratios are higher for those women who report they Inhale smoke than for those who do not inhale. 6. Mortality ratios for women tend to increase with the "tar" and nicotine content of the cigarette. 7. Mortality ratios- for female smokers are less than for male smokers. This may reflect differences in exposUre to cigarette smoke, such as starting smoking later, smoking cigarettes with lower "tar" and nicotine content, and smoking fewer cigarettes per day than men. 8. Women demonstrate the same dose-response 4 T TIMN 0048227

relationships with cigarette smoking as men. An increase in mortality occurs with an increase in number of cigarettes smoked per day, an earlier age of beginning cigarette smoking, a longer duration of smoking, inhalation of cigarette smoke, and a higher "tar" and nicotine content of the cigarette. Women who have smoking characteristics similar to men may experience mortality rates similar to men. Caution is necessary in drawing conclusions about the magnitude of either the relative risks or the absolute risks of smoking among women compared to men. Existence of a 25- to-30 year interval between the marked increase in consumption of cigarettes between men and women suggests that current figures may not yet constitute a demonstration of the maximal health effects of smoking in women. b MORBIDITY The 1979 Report of the Surgeon General summarized the information on smoking and morbidity as follows: 1. In general, female current cigarette smokers report more acute and chronic conditions including chronic bronchitis andJor emphysema, chronic sinusitis, peptic ulcer disease, and arteriosclerotic heart disease, than women who never smoked. 2. There is a dose-response relationship between the number of' cigarettes smoked per day and the frequency of reporting for most of the chronic conditions. 3. The age-adjusted incidence of acute conditions (e.g., influenza) foc women smokers is 20 percent higher for women who had ever smoked than for nonsmokers. Additional data from the Health Interview Survey (HIS) is presented: 1. Currently employed women who smoke cigarettes report more days lost from work due to illness and injury than working women who do not smoke. 2. Limitation' of activity is reported more commonly among women under the age of 65 who have ever smoked than among those who never smoked. CARDIOVASCULAR DISEASES Coronary heart disease is the major cause of death among both males and females in the U.S. population. The 1979 Surgeon General's Report clearly demonstrated the close 5 a TIT4N 0 48228

association of cigarette ;moking and increased coronary heart disease among males. This report reviews the evidence associating cigarette sm.)king and *cardiovascular disease in women: 1.' Coronary hear: disease, including acute myocardial infarction and chronic iachemic heart disease, occurs more , frequently in women wio smoke. In 'general, cigarette smoking increases the ri=k by a factor of about two, and in younger women cigarett-v smoking may increase the risk several fold. 2. Cigarette smoking is a major, independent risk factor for coronary heart disease in women; it also acts synergistically with other coronary heart disease risk factors producing a risk greater ;han the sum of the individual risks. 3. The use of or-t1 contraceptives by women cigarette smokers increases the ri ~k of a myocardial infarction by a factor of approximately t-:n. • 4. Women who smoke low "tar" and nicotine cigarettes experience less risk for coronary heart disease than women who smoke high ntar" an 1 nicotine cigarettes, but their risk is• still considerably great.r than that of, nonsmokers. 5. Increased levels of high-density lipoprotein (HDL) are correlated with a reduced risk for an acute myocardial infarction;. women cigareii,e smokers have decreased levels of HDL. 0 6. Cigarette smc,';ing is a major, independent risk factor for the deveiopwent of arteriosclerotic peripheral vascular disease in wome i. Smoking cessation improves the prognosis of - the disorder and has a favorable impact on vascular patency following reconstructive surgery. 7. Women cigarette ;mokers experience an increased risk for subarachnoid hemorrh2ge; the use of both cigarettes and oral contraceptives appear-, to- increase synergiqtically the risk for subarachnoid hemorrha_ie. 8. Women who smiCke cigarettes may be more likely to develop severe or maligoant hypertension than nonsmoking women. CANCER 1. Cigarette smolk ing Is causally associated with cancer of the lung, larynx; oral cavity, esophagus, and urinary bladder in women as well as in men; it Is associated with kidney cancer in women.

2. Cigarette smoking accounts for 18 percent of all cancers newly di=.gnosed and 25 percent of all cancer deaths in women. f n 1`)R0, 32,000 of the estimated 717,000 deaths, or over one-quarier of the deaths expected from lung cancer, will occur in worr en. 3. Women cigarette smokers have been reported to have between 2.5 and .5 times greater likelihood of developing lung cancer than ionsmoking women. 4. Among women the risk of developing lung cancer increases with increasing number of cigarettes smoked per day, duration of ;he smoking habit, depth of inhalation, "tar" and nicotine conta:nt of the cigarette smoked. The risk is inversely related to the age at which smoking began. 5. A dose -response relationship has been demonstrated between cigarette smoking and cancer of the lung, larynx, oral cavity, pancreas, = nd urinary bladder in women. 6. The rise in lung cancer death rates is currently much steeper In w)men that In men. It is projected that the age adjusted lung cancer death rate will surpass that of breast cancer in t;ie early 1980s. 7. The rapid increase in lung cancer rates in women is similar to but steeper than the rise seen in men approximately 25 , ' fears earlier. This probably reflects the fact that women first began to smoke in large numbers 25-30 years after the i tcrease in cigarette, smoking among men. Thus, neither men nor women are protected from developing lung cancer caused by cigarette smoking. 8. Cigarett: smoking has been causally related to all four of the major histologic types of lung cancer in both women and men, iorcluding epidermoid, small cell, large cell and adenocarcinoma. 9. The use of filter cigarettes and cigarettes with lower levels of "t ir" ~ and nicotine by women is correlated with a lower risk -if cancer of the lung and larynx compared to the use of *high "tar" and nicotine or unfiltered cigarettes. The risk posed by smoking low "tar" cigarettes, however, is c learly greater than that among females who never smoked. 10. After cessation of cigarette smoking, a woman's risk of developing ung and laryngeal cancer has been shown to drop slowly, equalfing that of nonsmokers after 10-15 years. 11. Excessive ingestion of alcohol acts synergistically with cigarette smok'ng to Increase the incidence of oral and laryngeal cancer in women. 7 0 0 ~ o°4g23o Ti1~

NON-NEOPLASTIC BRON,:HOPULMONARY DISEASES 1. Recent statis :ics indicate a rising death rate due to chronic obstructive twig disease (COLD ) among women. The data available demonstraie an excess risk of death from COLD among smoking women oier that of nonsmoking women. This excess risk is much • gre ,ter for heavy smokers than for light smokers. . 2. Women's total risk of COLD appears• to be somewhat lower than men's, a difference which may be due= to differences in prior smoking habits., 3. The prevalanc_ of chronic bronchitis varies directly with cigarette smoking, increasing with the number of cigarettes smoked per da;,. • 4. There is conflicting evidence. regarding differences in . the prevalence of chironic bronchitis in women and men. Several recent studies :uggest that there is no significant difference in the prevatence . of chronic bronchitis between male and female smokers. This may be the result, however, of increasingly similar smoking behavior of women and men. 5. The presence )f emphysema at autopsy exhibits a dose-response relationship with cigarette• smoking during life. 6. There_ is a close relationship between cigarette smoking and chronic cou_;h or chronic sputum production in women, which increases w th total pack-years smoked. 7. Women curren? smokers have poorer pulmonary function by spirometric testing than do female ex-smokers or nonsmoker.s, a relationsh'p .which . Is dose-related to the number of cigarettes smok ed. . 1 NTERACTf ON SETWEEN SM OKI NG AND OCCUPATt ONAL EXPOSURE : 1. The 1979 Surg-~on General's Report identified the ways In which . smoking cigarettes may interact with the occupational •environment. . They include: a) Facilitation of absorption • by physical contamination of cigarettes_, b) Transforma;,ion of workplace chemicals into more• ~toxic substances, c) Addition of the exposure to a toxic •constituent of tobacco smoke ' to a ;oncurrent exposure to the same constituent present in the =.rorkplace, d) Addition 'of , a health effect . due to J.- - ; ~:- - _ ;:. ,w."°:xr;. . .. . .................. ; -::x;: c: _- .••---••-'=.: ^•::.. - ;-~~~ -w.~ . . ..: ~:~»~ ~ ::~ ~'. ..........:::..... = .......:Y~~ . .... ~ r~ ----- --`-.:~._

environmental exposure to a similar health effect due to smoking, Yl e) Synergy of exposures, and f) Causation of accidents. 2. Women are entering occupational environments with greater frequency, and thus may be experiencing greater exposures to physical and chemical agents. 3. Cohorts of women with a greater prevalence of smoking are currently reaching the ages of maximal disease occurrence, replacing earlier cohorts with lower cigarette exposures. 4. Physiologic differences in hormonal status between males and females constitute a potential source of differing responses. 5. Women in the workplace who are pregnant present a nine-month exposure opportunity, including potential teratogenic and perinatal mortality effects. 6. Concurrent exposure of women to smoking and asbestos resulted In a clear excess of cancer of the lung. 7. Women smokers exposed to cotton dust run a higher risk of developing byssinosis, bronchitic syndromes, and abnormal pulmonary function tests than nonsmoking women. PREGNANCY 1. Babies born to women who smoke during pregnancy are, on the average, 200 grams lighter than babies born to comparable nonsmoking women. 2. The relationship between maternal smoking and reduced birth weight is independent of all other factors that influence birth weight including race, parity, maternal size, socioeconomic status, and sex of child; It is also independent of gestational age. 3. There is a dose-response relationship between maternal smoking and reduced birth weight; the more the women smokes during pregnancy, the greater the reduction in birth weight. 4. If a woman gives up smoking early during pregnancy, her risk of delivering a low birth weight baby approaches that of a nonsmoker. 5. The ratio of placental weight to birth weight increases with increasing levels of maternal smoking, reflecting a considerable decrease in mean birth weight and a slight increase in mean placental mass; this may represent an 9 TIMN 0048232

adaptation to relative fetal hypoxia. _6. The pattern- o_` fetal growth retardation that occurs with maternal smoking° .' is a decrease In all dimensions including body length, chest circumference, and head circumference. 7. Maternal smo-.ing during pregnancy may adversely affect the child's long-t-:rm. growth, intellectual development, and behavioral characteri ;tics. ~ 8. Maternal smoking during pregnancy exertss a direct growth-retarding- effect oR the` fetus; this effect does not appear to. be mediated by reduced maternal appetite, eating or weight gain. 9. The risk of s;Yontaneous abortion, fetal death; and neonatal death increases directly •with increasing levels of maternal smoking during pregnancy; Interaction of maternal smoking with other factors which increase perinatal mortality may result in an even gr :ater • risk. _ 10. Excess deaths of smokers' infants are found mainly in the coded• cause. categories. of "unknown" and ."anoxia" for fetal deaths., and the categories of "prematurity alone" and ."respiratory dif,ficulty" f)r neonatal deaths; this suggests that the excess deaths are Jue~ to problems : of the pregnancy, rather than.to abnormalities of the fetus or, neonate. 11. Increasing Ieyas of maternal smoking result. in a highly significant increase in the risk of abruptio placentae, placenta previa, bleeding eariy or late in pregnancy, premature and prolonged rupture of membranes, and preterm delivery-- all of which •carry high risks of perinatal loss. , - 12. Although there Is little effect• of maternal smoking art mean - gestation, the proportion of fetal deaths and live births that occur before. term- increases ~.directly with, maternal smoking level. . Up..to -14. percent of all preterm deliveries in the United States , may be '.attr.ibutable to maternal smoking. 13. The inc.idence of pre-eclampsia as decreased among women. who smoke during pregnancy; however, If pre-eclampsia develops in a smoking wc-man, the:: risk of perinatal _ mortality is markedly, increased. •. - . . . . 14. An infant's 'risk.~• of developing the "sudden infant death syndrome" is inco-eased by maternal smoking during pregnancy.. • • . " - 15. There are. insm fficient data to support a. judgement on whether maternal -.indJor paternal cigarette smoking Increases the risk of con;enitai malformations. 16. . Infants and c: ildren born ' to smoking mothers may experience more tong-terin morbidity than those born to non- ;__...~..~~.

smoking mothers; however, studies usually cannot distinguish between the effects of smoking during pregnancy and the effects of the infant's or child's passive exposure to cigarette smoke after birth. 17. Studies in women and men suggest that cigarette smoking may impair fertility. 18. Experimental studies on tobacco smoke, nicotine, carbon monoxide, polynuclear aromatic hydrocarbons, and other constituents of smoke help define pathways by which maternal smoking during pregnancy may exert its aforementioned effects. PEPTIC ULCER DISEASE The 1979 Surgeon Generalls Report included evidence that cigarette smoking in males was significantly associated with the incidence of peptic ulcer disease and increased the risk of dying from peptic ulcer disease by approximately 'twofold. The effect of smoking on pancreatic secretion and pyloric reflux demonstrated among men may provide a mechanism by which peptic ulcers develoo. 1.. Female smokers show a prevalence of peptic ulcer higher than that of nonsmokers by approximately two-fold. 2. The effect of cessation on healing is not known. 1 NTERACTIONS OF SMOKI NG WITH DRUGS, FOOD CONSTITUENTS AND RESPONSE TO DI.A:GNOSTiC TESTS Most published studies investigating the effects of cigarette smoking on drug use have been performed on mixed populations; factors specific for women have not been demonstrated to date. It has, however, been clearly demonstrated that women are prescribed and consume more prescription drugs -than men. 1.• Studies of selected drugs indicate that smoking may affect clinical responses and alter the dose required for an effective therapeutic result. 2. Smoking interacts with oral contraceptive use to increase the risk of myocardial infarction and subarachnoid hemorrhage. 3. Common clinical laboratory parameters are altered in smokers compared to nonsmokers; the health significance of these changes is unknown. 11 TIMN 0048234

concern over future social and economic roles. This stress may be the common mechanism producing the increased rates of smoking in some groups. 12. The factors associated with successful quitting by adolescents of either sex are lower number of cigarettes smoked per day, higher educational aspirations and achievement, greater acceptance of the health risk of smoking and having more nonsmokers among their friends. 13. it is possible that women and men modify their smoking in order to maintain a constant nicotine level. 14. Women are more likely than men to smoke in order to reduce stress. 15. Women at higher education and income levels are more likely to succeed in quitting. Additional factors associated with successful quitting are a strong commitment to change, the use of behavioral techniques and the reliability of social support for quitting. Women have been reported to show lower rates than men of successful cessation following organized cessation programs, a difference which is less apparent in those programs which include social support. , 0'r : 13 • ,.. ~IMN o04823

!-- b"`1  !T, e PATTERNS OF SNiOK! NG , . TIMN 0048237

PATTEt2N`i OF SMOKING I NTRODUc :TION This chapter traces the evolution of cigarette smoking among successive generations of American women and men during the twentieth century. The available evidence demonstrates that women have differed from men in their historical onset of widespread cigarette use, in the rate of diffusion of srnoking among eacii new birth cohort, in their intensity of cigarette smoking, arid their use of various types of cigarettes. Fou, main conclusions emerge from this analysis. First, althcugh men rapidly took up smoking during the early decades of this century, the proportion of adult female cigarette sriokers did not exceed one-quarter until the onset of LJor1d War I1. The peak intensity of smoking occurred among wom=n born after 1920. Secdnd, as a result of higher past rates r-f quitting and lower past rates of initiation among men, as w:lt as changes in the cigarette consumed, the smoking characteristics of women and men are now becoming increasingly similar. Third, the prevalence of cigarette smoking among adult American women and men is declining. This conclusion applies to all age groups, but with less certainty to the youngest generation of women. Fourth, increasing pliblic awareness of `the health consequences of smoking has resulted in significant changes in the nature of the cigarette product. Yet little is known about the effects of these product changes on the initiation, maintenance and cessation of -;moking, particularly among women. Since :he last review of cigarette smoking in the 1979 Report of the Surgeon General '(26), two new national surveys have been performed under the sponsorship of the National Center for Health Statistics and the National Institute of Education. This chapter relies in part on the recent, preliminary re_;ults of these surveys. The Rise of Cigarette Smoking: 1900 - 1950 Althoug h the use of cigarettes in the United States was observed as e-irty as 1854 (44, 50), consumption did not increase dramaHcally until after 1900. As shown in Figure 1, per capita consumption of all types of cigarettes increased by more than tenfold from 1900 to 1920. Despite a trarlsient 17 ., i ~ . e TIMN 0048238

b decline during the (;reat nepression, consumption increased from 665 cigarettes per capita in 1 n7f) to ?,57? cigarettes per capita in 1950 (52). A continuous, nationally representative series of smoking prevalence rates during the period 1900 to 1 QSn is not publicly available. Nevertheless, numerous sources can he pieced together to characterize the differential growth of cigarette smoking among women and men. Figure 2 depicts estimates of the percentage of male and female current cigarette smokers in the greater Milwaukee area, as compiled by the Milwaukee Journal (4n), In 1093, the first reported year of this survey, 51.R percent of males aged 1 R years and over smoked cigarettes. Sixty percent of male cigarette smokers also smoked pipes or cigars. In total, 97 percent of adult males used some type of tobacco (4n). Although earlier survey estimates of male smoking rates are unavailabie, it appears that the rise of cigarette consumption prior to 1023 reflected both the conversion of established male non-cigarette tobacco users to cigarette smoking and the recruitment of a new generation of younger male smokers during World War lo Innovations in cigarette production and marketing have been cited as influential fac- tors in this rapid growth (41, 50, 60). Camel cigarettes, a blend of lighter Purley smoking tobaccos with previously dominant Turkish cigarette tobaccos, were introduced in 1913 and within months attained a national market. Two similar brands, Lucky Strike and Chesterfield, followed in 101r, 'and 1910, respectively (41, 50, F9). Ruring World War 1, the lvar Industries °oard estimated that soldiers of the Allied Armies consumed FO to 7n percent more tobacco than they had used in civilian life (3n, 11). Cigarettes continued to dominate other forms of tobacco among male smokers throughout the 1020s and 1930s. Ry 1935, 62.5 percent of adult males in the greater P"ilwaukee area smoked cigarettes (Figure 2), while the percenta¢es of pipe and cigar users had declined substantialiv. Average cigarette consumotion freauency among men smokers increased from 3.7 packs per week in 1073 to d.R packs per week in 1935 (40). Consumption amon¢ men accelerated during World War II (Figures 1 and 2). In 1 Q44, more than 75 percent of cigarettes produced in the 11.5. were distributed to •overseas forces, tvpicatly for free or at low cost, to the point where subseeuent shortages developed in the domestic market (31, d1 ). Ry 1 o4R, F7.1 percent of adult males in the Milwaukee . 40

.W FIfaURE 2--Percentage of adult current cigarette smokers In the groater Milwaukee ana, 1924-1979.• 8® s o 50 40 30 20 10 0 t9 00 1910 s80 >930 19a0 1950 YEAR 5ource: Milwaukee Journal comsumer analyses (4p) ' Priorto 1941, the wording of th e question el iciting cigarette use and th e type of respondent are not recorded. From 1941 to 1954, men were asked, "Do you smoke cigarettes?" while all respondents were asked,"Do any women in your family smoke cigarettes ?" From 1955 to 1959, all respondents were asked, "Do any men (women) in yourhousehotd smoke cigarettes with (without) a filter tip?" From 1960 to 1965 and in 1967, both men and women were asked"Have you bought, for your own use, cigarettes with (without) a filter tip in the past 30 days?" In 1966 and from 1968 to 1979, both men and women were asked. "Have you bought, for your own use, cigarettes with (without) a filtertip in the past 7 days?" All percentages reflect adults aged 18 years and over. 20 T MEN i i WOM ML WAUCM SER JOIJR IES ~ >920 196o 1970 TIMN 0048241

n area smoked cigarettes (Figure 2). This estimate of the prevalence of cigarette use among urban rnen is confirmed by other local consumer surveys performed in that year. For example, in 1949, adult male smoking rates were 69.1 percent in Omaha, 67.4 percent in Birmingham, 69.4 percent in Philadelphia, 63.9 percent in Seattle, and 63.4 percent in San Jose (39). The growth of cigarette smoking among women occurred much later in the face of strong social taboos. Gottsegen noted that "the ultra smart set and women social leaders began to smoke at the turn of the century" (15). By 1906, American "girl stenographers° were reported smoking cigarettes clandestinely (5). By 1919, some younger women in New York were reported smoking at dinner parties "with a trace of defiance" (52). By 1922, New York women were smoking openly on the streets and in bus stops (10). The first advertisement showing a women smoking was Lorillard's 1919 publicity for Helmar cigarettes (46, 50). In 1926, a. young women in a Liggett and Myers' Chesterfield advertisement did not smoke but pleaded, "Blow some my way" (6). In April, 1927, a Philip Morris advertisement for Marlboro cigarettes noted that "women, when they smoke at all, quickly develop discriminating taste," and that Marlboro cigarettes were as "mild as .,,1ayR (2). In 1928, a Lucky Strike advertisement urged women to "reach for a Lucky instead of a sweet" (33, 43, 50). In 1934, Eleanor Roosevelt smoked cigarettes publicly (28). By, 1940, handbags and cosmetic compacts were typically designed to hold cigarettes (17). Although the Milwaukee Journat (40) reported that 16.7 percent of adult women smoked cigarettes in 1934 (Figure 2), prior estimates of womenIs smoking prevalence are sporadic. Wessel estimated that women consumed 5 percent of all cigarettes in 1924 (68). Moody's Investors Service estimated that women smoked 12 percent of cigarettes in 1929 (45). The average daily consumption of women smokers, as compared to men smokers, is not documented for that period. If men smokers consumed approximately twice as many cigarettes per day as women smokers (cf. the Milwaukee Journal's 1934 survey report that women's consumption frequency was 135 packs per year as compared to 244 packs per year for male smokers), and if the estimates of male smoking prevalence rates in Figure 2 are taken as nationally representative, and if there were approximately 5 percent more adult males than adult females during the 1920 to 1930 decade, then Wessel's 21 a TIMN 0048242

estimate yieids a 6 percent adult female smoking prevalence in 1024 and Moodyls estim ite yields a 16 nercent prevalence in 19?9 (53). The Milwaukee journal series in Figure 2 must be interpreted in light of changes in the type of survey respondent and the wordin:; of questions designed to elicit smoking practices (see can;.ion to FiRure- 1). Moreover, this urban population series may not be renresentative of all American women. Nevertheless, the publicly available survey data sources are consistent with the conclusion that smokinp rates among women did not exceed one-euarter until the onset o f 1Vor ld War 1 f. Rased * on 1n,000 ahplications for insurance oolicies during 1930 to 1440, Ley (34) estimated ai;e-standardized smoking rates of 63.9 per.;ent of men and 2A.R percent of women aged 15 years and cver. In 1935, Fortune Magazine, in the first nation-wide ;urvey (14), reported that 52.5 percent of adult men and 18.1 percent of adult women smoked cigarettes. (See Table 1 below). . Among those under 40 years of age, $5.5 percent •_,f inen and 2A.7 percent of -wornen y were smokers. Among thos-s over_ 40 years, 39.7 percent of ~ie6 'and--g.3 percent of wcmen were smokers. llrban-rural differences_ in smoking wer-_ significant. The proportion of smokers ranged' from 61.4 p`rcent of men and 31.2 percent of women in cities with population over one million, to 44.1 percent of men and R.f percent of women in rural areas with population under ?•,5M. A survey of 2511 urban women by the Market Research Corporatioir in 1Q37 reported 21; percent regular smokers and an additional 13 percent occasional s'niokers (49). After 1940, women's -;moking rates accelerated, as new generations of women, particularly younger women in urban areas, entered the labor force (see also title "Occuoation and Environment" in this Repoel. In 1 q44, the Gallup Poll reported 48 percent adult ' mAle smokers and 36 percent adult female • smokers (3). In 19-i9, the (:allup findings were 54 percent male and 33 percer t female (3). Local consumer surveys of urban areas in 1?4R revealed 37.6 percent adult women cigarette smokers in Milwaukee (see also Figure 2), 34.3 percent in Omaha, 35 ,F percent in Rirmingham, dF.7 percent in Philadelphia, 3R.-; percent in Seattle, ' and 3d.n percent in San Jose(39). Conover citing "trade journal" surveys in the three or fout, years prior to 1950, reported smoking prevatence rates: of 65 to 7fi percent among men and 4h to 45 percent among wom-_!n (11 ).

TABLE 1.-Estimates of the prevalence of regular cigarette smoking among adults, United States, selected national surveys, 1935 - 1979. Ye-tr Femai e !da l es 19:5 18.1 52.5 1955 24.5 52.6 1965 33.3 51.1 197d 37.1 43.5 19 7-'• 37.9 42.7 197t 32.4 41.9 1978 29.9 37.0 1979 28.2 36.9 Sc)URCE: (14,18,56,58-61) Data for 1978 are revisions of preliminary estimates reported in (26). Data for 1979 are preliminary estimates based on a sample of over 13,00) interviews conducted during January - June 1979, provided by Heatta Interview Survey, National Center for Health Statistics. 1955 data ~•epresent persons 18 years and over. 1976 data represent pcrsons 20 years and over. Estimates for the years 1965, 1970, 1974, 1978 and 1979 represent persons 17 years and over. .^ 23 TIMN 0048244

Although the differential growth of cigarette use among various socioeconomic group ; is not well documented, the available data during this p-wiod suggest that male smoking rates declined with increashg income, while the relation of women's smoking to income was less clear. The Milwaukee journai in 1945 noted 58 percent of men with -monthly rents over $50 were smokers, and 75 percent of men with rents under $30 per month (40)we*,•e smokers. Among women, the corresponding proportions were 32 and 37 percent respectively._ In Mill's and. Porter's 1947 survey of Columbus, Ohio (.38), 28.3 percent of white females and 64.9 percent white males smoked cigarett-;s, whereas 36.4 percent black females and • 68.9 percent black males smoked cigarettes (estimates calculated from the age •distribution data provided in Table 6 of (38). Kirchoff and Rigdon, in a survey of over 21,000 patients, visitors, •?nd employees of • hospitals in Houston and Galveston, noted 'that 63.2 percent white males, and 33.4 percent white fem=-,les, 66.3 percent• black males, and 32.2 black females smoke•f cigarettes (32). All of the above findings reinforce the conclusion that the onset of widespread cigirette use, among women lagged behind that of men by 25 to 30 years. This historical detay in the growth of cigarette -moking among women has also been documented for the Unit=d Kingdom (10,48,51). The Emergence of Filtertip Ci-;arettes: 1951-1963

At the same time, both women and rnen rapidly converted to filtertip cigarettes. By 1958, filter cigarette use prevailed among 61 percent of women smokers and 42 percent of men smokers in Milwaukee, 54 percent of women smokers and 43 percent of men smokers in Omaha, 53 percent of women smokers and 47 percent of rnen smokers in Washington, D.C., and 59 percent of women smokers and 42 percent of men smokers in San Jose (39). In a nation-wide 1964 survey reported by the National Clearinghouse for Smoking and Health (62), 79 percent of adult female smokers and 54 percent of adult male smokers used filter cigarettes. Increasing Public Health Awareness: 1964-1979 Per capita consumption reached a peak of 4,336 in 1963 (Figure 1). It declined transiently after the appearance in January 1964 of the first Report of the Advisory Committee to the Surgeon General (54). Per capita consumption continued to decline during the subsequent period af--increased publicity concerning the health hazards of smoking (26,29). Since 1975, per capita consumption has declined at an average rate of 1.4 percent annually. The most recent 1979 estimate of 3,900 cigarettes per capita closely approxim ates that observed in 1952. Table 1 summarizes the results of selected, nationally rcpresentative surveys of adult cigarette use during the period 1935 to 1979. Except for the Fortune. survey of 1935 (14) and the supplement to the Current Population Survey in 1955 (18), these data were collected under the sponsorship of the National Center for Health Statistics. The results of other recent national surveys of adult cigarette use . (3,4,55,57,58,62,63,65), revealing very similar trends in the prevalence of smoking, were described in the 1979 Surgeon General's Report (26). Among adult males, the prevalence of regular cigarette use has declined continuously since 1965, with mGre marked decreases in the intervals 1965 to 1970 and 1976 to 1978. (The absolute standard errors for all National Center for Health Statistics estimates in this table are less than 0.3 percent.) Among adult women, the direction of change in smoking prevalence is less clear. The estimates for the interval 1976 to 1979, however, suggest a recent downturn. The preliminary 1979 estimate of 32.3 percent for the overall prevalence of adult cigarette smoking among both sexes 25 TIMN 0048246

ep.resents the lowest recorded vatue in at least 45 years. i'ite, overall prevalence of cigarette smoking. in the 1935 ortune Magazine was 37.3 percent among adults of both :xes.) These patterns of change ii smoking prevalence applied ~ both white and black adul~:s. For white men, the -evalence of regular smoking de-; Iined from 51.5 percent in M to 36.3 percent in 1979. F•ir black men, the prevalence = regular smoking declined frow 60.8 percent in 1965 to ?.0 percent •in 1979. For white women, smoking prevalence :clined from 34.2 percent in 19t-5. to 28.2' percent in 1979. fr black women smoking prev=lence declined from 34.4 rcent in 1965 to 28.9 percent 11 1979. Racial differences cigarette use are discussed -in rreater detail In the chapter this report entitled "Psychosoci-,l and Behavioral Aspects of ioking in Women." • I Although the Milwaukee are . data for 1964 to 1979 do t elosely match these national estimates, Figure 2 does, ow a marked decline in smoking rates for bot(t sexes during 64 to 1970, a deceleration i.i the decline of smoking :valence ••during 1971 to 1975, and a resumption of the cline in prevalence among men ir. the last four years. The cessation of cigare's:e smoking has been a .nificant factor in explaining this overall decline in smoking svaience (26): Colurnn (1) of T?hle 2 presents estimates of : percentage of recent • smokers -vho made a"fairly serious empt to quit" within one year of the interview date. :cent smokers Include all current smokers plus those former okers reported to have stopped within one year of erview.) Column (ii) shows +rhat proportion of those empting to quit regarded • themselves as former smokers. urnn (iii) shows the proportioui of all recent smokers rether or not they attempted or succeeded quitting) who orted themselves as recent forwer smokers. These data essarily reflect respondents' sel P-assessment of both the iousness of a quit attempt and their degree of success. •ertheless, they do provide an indication of the resentative smoker's annual pro~iability of attempting to :, the probability of successful cessation given a quit :mpt, and the overall annual smo':ing cessation rate. (The )lute standard errors in Table 4 are approximately 1.0 ;ent, 1.5 percent, and 0.3-0.5 pe,cent for columns ( i),( ii), (i.ii), respectively.) 26 __...~_...... _ _ ...,z.....~.. ,,,•......~;...,~,- - - "' ' .......~ ..........._...r..~ .--... ~

TABLE 2.-Estimated rates of attempted and successful quitting among adult, recent cigarette smokers, United States, 1970 - 1979. *7 • f Womell 1970 1975 1978 1979 Men 1970 1975 1973 1975 (i) Percent of All Recent Smokers Who Attempted to Quit in Past Year (ii) Percent of Smokers Attempting to Quit in Past Year Who Reported Successfully Quitting (iii) Percent of All Recent Smokers Who Reported Successfully Quitting in Past Year 40.8 21.3 8.7 30.2 19.5 5.9 32.7 18.8 6.2 32.9 21.6 7.0 44.4 26.4 11.7 28.3 20.1 5.7 29.1 21.5 6.3 31.4 21.3 6.7 `'OURCE: 1970 and 1975 data from surveys of persons aged 21 years and ove,,, conducted by National Clearinghouse for Smoking and-Heaith (63,65). 1978 and 1979 data from the Health Interview Survey of per- son; aged 17 years and over, conducted by the U.S. National Center for Health Statistics (61). 1979 data are preliminary estimates based on interviews during January - June of that year. i 27 16 TIMN 0048248

. -- - -- ~-` , r ~---_-_ ~ ~~- -~` i:: - - ~:

TABLE 3.-Estimated percentage distribution of adult current regular cigarette smokers according to f.t.c. 'tart content of primary brand, United Stated 1970 - 1979. Year Less Than 5.0 to 10.0 to 15.0 to 20.0 mg 5.0 mg 9.9 mg 14.9 mg 19.9 mg or More Women 1970 9.7 2.0 6.8 67.1 23.4 1975 1.2 1.2 15.0 75.1 7.5 1978 5.3 8.8 21.1 59.2 5.7 1979 5.6 9.5 23.4 55.4 6.1 Men 1970 0.2 0.9 1.8 61.3 28.1 1975 0.6 1.1 11.0 68.1 19.2 1978 3.3 6.2 13.5 63.5 13.6 1979 2.2 8.5 17.0 60.1 11.8 SOURCE: National Clearinghouse for Smoking and Health (63,65), National Center for Health Statistires (61). 1979 data are preliminary estimates provided by the National Center for Health Statistics. 1970 and 1975 data represent adults aged 21 years and over. 1978 and 1979 data represent a.dults aged 17 years and over. Estimates exclude those with unknown primary cigarette brand. . 6 29 4 TIMN 0048250 -

TABLE 4.-Estimated percenta-e distribution of adult current cigarette Smokers according =o reported daily consumption freauency, United States, 1965 - 1979. Year Perce. t Smoking Less rban.15. Cigar=ttes per Day Percent Smoking 25 Cigarettes or More per Day Women - 1965 4A .5 13.7 1970 3~.1 18.0 1974 3E.7 18.5 1976 36.5 • .19.6 1978 36.0, 21.0 1979 °•.6 22.4 Males 1965' 2:1' .6 24.5 - `t970°- ' 27.8 ; 27.7 1974" 26.3 '.• 30.6 1976 24'. 2 ., _ 31.1' 1978 23.4.. . 34.2 1979 26.4 32.2 • SOURCE: (26,56,58-61). Data for 1976 represent persons aged 20 years and over. A11 other years eepresent persons aged.17 years and over. Data for 1979 are preliminary estimates based on Interviews conducted during January - June of thst year, provided by the Health interview Survey, National Center for Heaith Statistics.

Numerous epidemiological studies and other survey ; performed during the period 1950 to 1965 have shown tha for both sexes, especially for women, the proportion of heavq smokers was larger among the younger age groups (16,18,21,22,24,32,3R,6 2,F3). These findings applied to current daily smoking and lifetime maximum cigarette consumption. They are consistent with the hypothesis that , regular smokers in past decades consumed fewer cigarettes per day than contemporary smokers. The empirical relationships between rates of smoking cessation (Table 2), changes in F.T.C. "tar" and nicotine delivery of cigarettes (Table 3), and increases in daily : cigarette consumption (Table 4) are poorly understood (27). It is not known whether smokers of the lowest "tar" cigarettes are more or less likely to attempt to quit, or to succeed in auitting, than smokers of conventional filtertip or nonfilter cigarettes. The extent to which the act of switching to a lower "tar" cigarette may serve as a substitute for quitting may differ among women and men. The observed increase in daily cigarette consumption among current smokers could represent the effect of: higher cessation rates among lighter smokers; an increase in the smoking frequency of continuing smokers; or an increased smoking frequency of new entrants into the smoking population; or a combination of these effects (26). The relationship of these possible ~ mechanisms to the observed increase in the proportion of fiitertip cigarette and low "tar" cigarette smokers is not well ~ elucidated. Exposure to Cigarette Smoke Among Successive Pirth Cohorts Figures ? and 4 depict estimates of the prevalence of current cigarette smoking from 1 9M to 10718 among successive birth cohorts of men and women. Each continuously graphed time series corresoonds to individuals born during a particular decade. For example, among women horn from 1931 to 1940 (Figure 4), who are now 4in to 49 vears old, the prevalence of smoking rose raoidiy during the post World War If period and reached a peak of 45 percent by 1063. Thereafter, their overall prevalence of smoking declined to 30 percent in 1978. These prevalence data were constructed from the reported lifetime smoking histories of over 13,000 respondents to the Health Interview Survey during July to Pecember, 1978. (For related applications of this methodology, see 9,20,17). 31 .

FfGURE 3.-Changes in the prevalence of cigarette smoking among successive birth cohorts of men, 1900-1978. 1921-30 0 1900 1910 U 11 911-20 ' ; 931-40 ----~ 0 ~ - ~ t90t- 10,` ~ ~ 0 ( y1900 I \ ` ~ ~ i . ' ~ 1! a YEAR Source: Calculated from the results of over 13.000 interviews conducted during the Iast two Quarters of 1973, provided by Division ot Health Interview Statistics. U.S. National Center for Health Statistics. ?,7 - TIMN 0048254 .

born before 1910, (b) women horn between 1 Q21 and 1940, who are now anproaching 40 to 50 years of age, experienced the highest smoking prevalence rates. These women have not yet reached the age where the absolute excess deaths of smokers over nonsmokers are expected to become substantial (1 ). (c) Among successive cohorts of men and women, the age of peak smoking prevalence has declined. Among younger cohorts, the peak smoking prevalence rates are declining, although the effect is less marked for women. Men born between 1911 and 1 Q?A reached a peak smoking prevalence of 71 percent during 1046 to 1948, while those horn 1941 to 1950 reached a peak smoking prevalence of 59 percent in 1968 to 1969. `.`!omen born 1021 to 1 Q3n reached a peak prevalence of 44 percent in 195R to 190, while those born in 1041 to 1950 reached a peak smoking prevalence of a1 percent in 197n to 1 073. (d) Among men born 1051 to 1960, the rate of increase of smoking prevalence was slower than in previous cohorts. This slowing of the diffusion of smoking practices was coincident with the increased publicity concerning the health risks of smoking and the relatively high rate of etuitting smoking among adult maies in the late 1960s. A similar effect is not clearly discernible for young women in this cohort. In both sexes, who are now aporoaching ages ?n to 29, the prevalence of smoking has apparently peaked. Smoking rates among men and women in this age group are now nearly indistinguishahle. • Figure 5 depicts the mean age of starting regular smoking among successive birth cohorts, calculated from the same data as for Figures 3 and 4. The age of onset of smoking among women declined continuously during this century, to the point where it is nearly indistinguishable from that of men. As a result, each successive cohort of lifelong continuing women smokers will have an increasing number of years of exposure to cigarette smoke. Figure F depicts the accumulated years of cigarette smoking per capita, up to 1978, for each birth cohort. These magnitudes c6rrespond to the total areas under each cohort prevalence curve in Figures 3 and 4. Among women, individuals born 1911 to 192n have thus far experienced the largest total exposure per capita. However, as seen from Figure 4, unless the smoking prevalence rates of women born during 1921 to 1940 decline more rapidly in the future, the lifetime exposure of these latter cohorts is likely to exceed that of the 1911 to 1920 cohort. It is not clear, however, whether the lifefime exposure of men born from 1921 to 35 TIMN 0048256

FIGURE 5.-Mean age of onset of regular smoking among successive birth cohorts of women and men. ' 40 L ~ 35 v ~ 30 10 I T -1900 190110 191-201921-301931441941-501951-60 Bir :h Cohort Source: See notes to Figures 3 and 4. ~-~-----~

FIGURE 6.-Accumuiated years of cigarette smoking per person among successive birth cohorts of women and men, 1978. 1 z W 2 ? 1 -1900 1901-10 1911-20 1921-3G 1931-40 1941-50 1951-60 . Birth Cohort Source: See notes to figures 3 and 4. 37 0 , TIMN 0048258

1940, now 50 to 69 ,,ears of age, will exceed that of previous generations. With each successive cohort, the ratio of female to male exposire increasingiy approaches one. As a result of the rapid diffusion of filtertip cigarettes after 1950 (FiAure 1)-, each successive birth cohort was exposed to a different proportion of filtertip and nonfilter cigarettes. De-,aii"s of the respondent's past history of cigarette brand use were not obtained in the 1978 Health Interview Survey. Such data, however, are available from a series of over 4,000 inte:•views of current and former smokers aged 71 years, and aver, conducted by the National Clearinghouse for Smokin:; and Health in 1975 (65). Figure 7 depicts the proportion of years of • smoking filtertip cigarettes among comparable birth cohorts (the youngest birth cohorts necessarily differ). Among men, there is a distinct, monotonically increasing relation between the proportion of filtertip 1 cigarette exposuee and birth date. The corresnonding relationship is confound--d among women born before 1930 reflect. their lower smo'1ng cessation rates and, therefore, their continued use of iilter cigarettes. A woman born in 19.25, for exampie, who began smoking at age 21 (Figure 5), and who switched to fiiteiftip.,ciltarettes in 1957 (Figure 1), has now been smoking filtertip cigatette-s for over two thirds of her smoking career ar.drdiL.perce_nt of her entire life. The prevalence of cigarette smokirig; age -of initiation, lifetime duration of. smok ing, and the extent of use. of various types of cigarettes are not the only measures of cigarette smoke exposure among -. particular population. Trends in depth of inhalation, fraetion of cigarette actually smoked, and other dimensions of the style of smoking al so affect smoke exposure. However, a4 discussed in the 1Q79 Surgeon General's Report (26), i;iese are difficult to determine from survey data. In view 'o f the concern that the accuracy of contemporaneous survey r-,ports of daily cigarette "consumption past accounts of the - time- -course-of - daily cigarette consumption would be difficult to assess accurately (F7). • Nevertheless, the evidenc= presented in the previous section is consistent with the conci.sion that the average daily cigarette consumption among regular cigarette users has increased among each successive birth cohort. As discussed in the 1979 report of cigarette smoFing, trends in depth of- inhaiation, fraction of cigarette actually smoked, and other dimensions of the style of smoking are difficult to gauge from survey data (26). 38 : ~ ::: _::_;::::: ::::::: : ::~;: ~ °: ~ # ~:~: ~;;~: ._ ._.......... _.-............ _.... _.... __. - -_ - -- = -_ - . ~ - _ _ ....-_.._~_ _ . . ~ __. . . .... ._.._._.........._..._ .................................. ................ _...... .............~ ..........~ ..._..... _........ _-_......._..•-- -_ _ .-._ ----________------------ - - ------------- - ........; ................. ... _ - - - - - _ ~--°== ..........__.......... _ .. .. ..................... _..._....... _..... -.. =- - - - - - - .... ...... . ~ ._... .... _... _ _ ._... ...- ...._;,_ ~-....._.........__ . .... ........ ::. = ......._ ......._......................................... - s.: -,..... - -_- °- - = ~ _- ~ s;.............. ~:::::::::: _ . ...- :T. --.-~ ..,...-.`~-::. -. -~:::: ~ -~:=.:..-:.......... . ........_.,~•-•- ._.... ......... . ....~::.:::.:::~: .. ::::::::•:::~::--------------- ---- ---- ------------------ -- ----- --- ---- - - ~ _ ------- --------- - -- --- -- - - - -_=_~_~_ ===~_====_ _-_: _ ~~ _ _...._..._ _ __._. _ ._ __...._.-......._~.._..... ----------- - _ ...::::: ..--:::::::~ ~::~:::~:: : - ._........................ . - . .._......... _ _........ _........ ; :~ .....--.... - :_ - =__ = -_ ========------___ 25 _ -..._----..-.... _---.--.-- ............... -_._....::_ IMN 0 0 ::..::: =--::- :- ::-:::: =:-::~::: T :::::::::::..:...r.................. - --------- ......-.............. ... ........_... .............. ...-..... ._..._.:...-:.. =:_.........

t-iGlJRE 7.-Proportion of years smoking fiitertip cigarettes among s-iccessive birth cohorts of women and men, 1975. 100 U- t ;_ _; 90 ~ z '09)80. 3 a ~ 1 1 1 s: 70 ' .... C 2 --•• .~.. Y 5) r l r r 9 i U) 40 t r i ~ Cc 30 ~ ~ ? 020 r ... .c 10 - r I ~ d 0 + -1900 1 90110 1911-20 1921-30 1931-40 1941-50 1951-54 Birth Cohort Source: Calculated from the resutts of over 4.000 smoking histories of men and women who had ever smoked, cot'ected by National Clearinghouse for Smoking and HeaOh (65). 39 TIMN 0048260

TABLE 5.-Estimated percentage of current, regular cigarette smokers, Ages 12 - 18, United States, 1968 - 1979. .r ; ~ .. .~ : ~ i , ~ i ~ . ,> u, ~ t Year Femaies Ages 12-14 Ages 15-16 Ages 17-18 1968 0.6 9.6 18.6 1970 3.0 14.4 22.8 1972 2.8 16.3 25.3 1974 4.9 20.2 25.9 1979 4.4 11.8 26.2 Maies 1968 2.9 17.0 30.2 1970 5.7 19.5 37.3 1972 4.6 17.8 30.2 1974 4.2 18.1 31.0 1979 3.2 13.5 , 19.3 SOURCE: Natton-wide surveys performed by National Clearinghouse for Smoking and Health, 1968-1974 (64), and National Institute of Education , 1979. Current regular smokers in all surveys include all those who smoke cigarettes at least weekly. In 1979, approzimateiy 90 percent of current regular smokers used cigarettes on a daily basis. For 1979 only, 29.7 percent males and 31.9 percent females, aged 19, were reported as regular smokers. 41 sr TIMN 0048261

CIGARETTE SMOKING AMONG YOUNG WnMEN The more marked decline in peak smoking prevalence among men born between 1951 and. 1 Q61, now approaching ?A to 2Q years of age-, reflected a slowing in the rate of initiation of smoking that was not •-bserved in women of the same age group. This trend appe-,rs to be continuing In the next birth cohort. - . - . . : ... - Table 5 reports =he results of nation-wide surveys of teenage cigarette smokifg during 1968 to. 1979. The ~ most recent survey, conducted by the National Institute of Education during' -tate 1978 and early 1979, presents the preliminary resuits ' of over. 2,600 ' telephone interviews of individuais aged 12 to 19 years. in this survey, but not in the others reported in i able , 5, women and men 19 years of 'age were also interview;d. Otherwise, the survey sampling tachniq,ues,:ind ieterview quesiions regarding smokinyt. practices ; wer.e.• the', sime,, for'~ai.f ~~uie.:surveys... (See. notes*- to Table S): The; data ~ in Table .5 confirm the conclusion :that. the rate of initl.tiorr `-of" • smoking imonR=" everr the' youngest men is declinlnR, * in . effect 'that' is not -presentt 'am~ong' young women. These results must be interp~eted irt tiRht " of sampling variability. (The absolute 'standard errors of the 197Q estimates for ages 15-1 15.and 17-18 are about 2 percent.) As in adult surveys, non-response biases must also be considered. . Nevertheless, the findings in ' Table 5 are consistent with other na;:ion-wide estimates of smoking rates among 'young women , and men. The prevalence of current regular smoking among r-;spondents 17 to 19 years of age in this survey was 2R.1 percent for females and 72.9 percent for males. The compara;i le rates for women and men aged 17 to 19 from the Health In terview Survey were 29.2 percent and 27.5 percent, respectively. An analysis of the growth of smoking prevalence amona this group, performed in the same manner as that of Figures 3 and 4, suggested that smoking rates among this group -)f women grew rapidly and exceeded those of men by 1975. The future smoking habits of this generation of young wom-;n cannot be accurately pr.edicted. . Smoking among te snage women is discussed in greater detail in the chapter entitled "i'sychosociai and Rehavioral - Aspects of Smoking in ':1---men" in this Report.

1. Women have -!lffered from men in their historical onset of widespread cigarette use, in the rate of diffusion of smoking among each ne=.r birth cohort, in their Intensity of cigarette smoking and th-:ir use of various typess of cigarettes. 2. Men took u.- cigarette smoking rapidly at the beginning of the twentieth century, especially. during World War 1. Cigarettes rapi-aly replaced other forms of tobacco. By 1925, approximately 50 percent of adult males were cigarette smokers. Sm sking among men acceleratad rapidly during World War ti. .ty 1949, the prevalence of cigarette use among men approach :d 70 percent in some urban areas. 3. The onset •if widespread cigarette use among women lagged behind th it of men. by 25 to 30 years. The proportion of adult women smoking cigarettes did not exceed one-quarter until the oniet of. World War, 11. . 4. Between 1951 and.1963, increasing proportions of women and men smokers converted to filtertip cigarettes. By 1964, 79 percent of adf ilt women smokers and 54 percent' of adult- men smokers used- fiiter-cigarettes.--, .._ .- : 5. ~ After reachii-g. a, peak . value of 4,336 In 1963, annual per capita consuilliption of cigarettes declined In .1964, T 968-70,,_ and in tiie p-eriod since 1975. The most recent estimate ~-of 3,900 cigarettes _ per capita .in 1979- is approximately equal tc uiat observed - in'1952. 6. From 1965 t•i 1978, the proportion of adult men cigarette smokers decli,ied . from 51 to 38 percent. The preliminary estimate of adult ments smoking prevalence for 1979 is 36.9 percent. :'rom 1965 to 1976, the proportion of adult women smokers renalned virtually unchanged at 32 to 33 percent. Since 1976, ?ie proportion of women smokers has declined to below 30 percent. For 1979, the preliminary estimate of adult women's smoking prevalence is 28.2 percent. The overall smoking preVtienee of .32.3 percent for both sexes in 1979 represents the lowest recorded value in* at least 45 years. . 7. The proportio.i of .aduit smokers attempting to quit smoking declined from 1 i70 to 1975, but increased in 1978- 1979. In contrast to past years, the proportions of women and men now attempting to quit smoking, and their reported quitting rates, are indi-;tinguishable. Approximately one in three adult smokers no-v makes a serious attempt to quit smoking during the cour ;e of a year. Approximately one in five of those who attempt to quit subsequently succeed. 8. The proportic.i of adult smokers using lower star1° and nicotine brands has increased substantially. In 1979, 39

: > f percent of adult women smokers and 23 percent of adult men smokers reported primary brands with F.T.C. "tar" delivery less than 15.0 milligrams. It is not known whether smokers of the lowest *tar" cigarettes are more or less likely to zttempt to quit smoking, or to succeed in auitting, than smokers of conventional filtertip or non-fiiter cigarettes. 9. The average number of cigarettes smoked by women and men current smokers has increased. The relationship of this finding to recent declines in the average F.T.C. "tar" and nicotine deliveries of cigarettes is not well understood. 10. With each successive generation, the smoking characteristics of women and men have become increasingly similar. 11. Among women, the average age of onset of regular smoking progressively declined with each successive birth cohort--from 35 years of age for those born before 1900, to 16 years' of age among those born 1951 to 1960. The average ige of onset of regular smoking among young women i s now virtual ly identical to that of young men. 12. Maximum smoking prevalence rates have declined substantially in • recent birth cohorts of men. Men born 1931• to 1940 reached a peak smoking proportion of 61 percent during 1960-62, while men born 1941 to 1950 reached a peak smoking proportion of 58 percent in 1968-69. Men born 1951 to 1960 reached a peak smoking proportion of 40 percent in 1976. Among recent cohorts of women, peak smoking prevalence rates ~ have declined to a much smal ler extent. Women born 1931 to 1940 reached a peak smoking proportion of 45 percent in 1966-68, while women born 1941 to 1950 reached a peak smoking proportion of 41 percent in 1970-73. Women born 1951 to 1960 reached a peak smoking proportion of 38 percent in 1976. Among the generation born 1951 to 1960, the proportions of women and men smoking cigarettes are now virtually identical. 13. The proportions of women and men smokers in each age group have declined. Among those born before 1951, this decline in smoking prevalence resulted mainly from smoking cessation. By contrast, the observed decline in smoking prevalence among younger men born 1951 to 1960 has resulted from both smoking cessation and a lower rate of smoking initiation. This decline in the rate of onset of smoking among young men has not been observed for young women. 14. Recent survey data on adolescent smoking habits reveal that by ages 17 to 19, smoking prevalence among women exceeds that of men. This finding supports the 43 TIMN 0048264,

~. ..... ._ ` ~ ; i ; ; ; ~ t ' j conelusiort that the rate of Initiation of smoking among young men--but not that of young women®-is declining. n The future cigarette nse of the y_oungest=Senerations.• of women is.uncer- s lain. 15. With each successive birth cohort, the accumulated years of cigarette smoking per woman has progressively approached the accumulated years of cigarette smoking per man. Each successive birth cohort has also experienced progessively smaller sex differences in the fraction of lifetime years of smoking that represents filtertip cigarette use. 16. Among men born during this century, each successive birth cohort has thus far .experienced fewer cumulative years of cigarette.- smok•ing, . higher prop.artionate exposure to fiitertip cigarettes, and lower smoking prevalence rates. This. relationship between birth date and cigarette smoke exposure does not hold for women. Women born 1921 to 1940 have experienced substantially higher smoking prevalence rates •that earlier generations. Unless they auit smoking in substantial numbers, these women, currently aged 40 to 59, wili surpass older women in total years of cigarette smoking per capita, the total years of nonfiiter cigarette smoking per capita, and in the total number of cigarettes smoked. The health consequences of this enhanced exposure to cigarette smoke among women are likely to be more prominent in the coming decades. a 44 TIMN 0048.265 '

PATTERNS OF SMOKING: REFERENCES V1 (1) (2) r ~ (3) (4) (5) (6) A (7) ; r , ~ . , ;. (8) i ; > , ADAMS, E.E. Mortality. in: Smoking and Health. A Report of the Surgeon General. U.S. Depart- ment of Health, Education, and Welfare. January 1979, pp. 2-1 to 2-47. ADVERTISING & SELLING. Marlboro Makes a Direct Appeal. Advertising and Selling 8:25, 'March 23, 1927. AMERICAN INSTITUTE OF PUBLIC OPINION (GALLUP). The Gallup Poll Public Opinion, 1935-1971 Series, pp. 477-1501; 1972-1977 Series, pp. 274-1203. AMERICAN INSTITUTE OF PUBLIC OPINION (GALLUP). The Gallup Opinion Index, September 1970, July 1971, July 1972, June 1978. BAIN, J., JR., WERNER, C. Cigarettes in Fact and Fancy. Boston, H.M. Caldwell Co., 1906. BONNER, L. Why Cigarette Makers Donit Advertise to Women. Advertising & Selling 7: 21, October 20, 1926. BORDEN, N.H. The Economic Effects of Advertising, Chapter Vtt. The Effect of Advertising on the Demand for Tobacco Products -- Cigarettes. .Chicago, Richard 0. Irwin, Inc., 1944, p. 207- 249. BURKE, H. Women Cigarette Fiends. Ladies Home Journal 39: 19, J une 1922. (9) BURBANK, F. U.S. Lung Cancer Death Rates Begin to Rise Proportionately More Rapidly For Females Than for Males: A Dose-Response Effect? Journal of Chronic Diseases 25: 473-479, 1972. (10) CAiRNS, J. The Cancer Problem. Scientific American 233(5): 64-78, November 1975. (11 ) CONOVER, A.G. Discussion of Etcno Jackson's Paper. Journal of Farm Economics 32(4, part 2): 923-924, November 1950. (12) CONSUMERS UNION. Cigarette Smoking and Lung Cancer. Consumer Reports 19: 54-92, February 1954. (13) COWELL, M.J., HIRST, B.L. Mortality Differences Between Smokers and NonSmokers. Worcester, Massachusetts, State Mutual Life Insurance Company of America, October 22, 1979. 45 TIMN 0048266

(14) FORTUNE MAGAZINE. The Fortune Survey. Ill. Cigarettes. 12(1 ): 68, 11 -116, July 1935. (15) GOTTSEGEN, J.J. Tobacco. A Study of Its Con- sumption in the United States. New York, Pitman Publishing Corp., 1940. (16) GRAHAM, E.A. Primary Cancer of the Lung with Special Consideration of Its Etiology. Bulletin of the New York Academy of Medicine 27(5): 261 -276, May 1951. (17) HAENSZEL, 'lV., SHHrtK1N, M.B. Smoking Patterns and Epidemiology of Lung Cancer in the United States: Are They Compatible? Journal of the National Cancer Institute 16(6): 1417-1441, June 1956. (18) HAENSZEL, W., SHIPvSKtN, M.B., MILLER, H.P. Tobacco Smoking Patterns in the United States. U.S. _Department of Health, Education and We1 fare, Public Health, Monograph No. 45, 1956. (19) HAMMOND, E.C. Smoking in Relation to the Death Rates of One Million Men and Women. National Cancer Institute Monographs 19: 127-204, January 1966. (20) HAMMOND, E.C. Life Expectancy of American 'rlen in Relation to Their Smoking Habits. Journal of - the National Cancer Institute 43 (4):•` 951 -962, October 1969. (21 ) HAMMOND, E.C., GARFINKEL, L. Smoking Habits of Men and Women. Journal of the National Cancer Institute 27: 419-442, 1961. (22) HAMMOND, E.C., GARFINKEL, L. Changes in Cigarette Smoking. Journal of the National Cancer Institute 33: 49-64, 1964. (23) HAMMOND, E.C., GARFINKEL, L. Influence of Health on Smoking Habits. National Cancer Institute Monographs 19: 289-285, January 1966. (24) HAMMOND, E.C., GARFINKEL, L. Changes in Cigarette Smoking 1959-1965. American Journal of Public Health 58(1 ): 30-45, January 1968. (25) HAMMOND, E.C., HORN, D. The Relationship Between Human Smoking Habits and Death Rates. Journal of the American Medical Association 155: 1316- 1328, 1328, 1954. 46 TIMN 0048267

(26) HARRIS, f.E. Cigarette Smoking in the United States, 1950-1978. In: Smoking and Heafth; A Report of the Surgeon General. U.S. Department of Health, Education, and Wet fare. January 1979, pp. A1 -A29. (27) HARRIS, J.E. Public Policy Issues in the Promotion of Less Hazardous Cigarettes. In: Toward a Less Hazardous Cigarette. Cold Spring Harbor Laboratory, Banbury Center (28) (29) Reports HOOVER, (In I.H. press) Hail to the Chief. Saturday Evening Post May 5, 1934. IPPOLITO, R.A., MURPHY, R.D., SANT, D. Staff Report on Consumer Responses to Cigarette Health Information. U.S. Federal Trade Commission Bureau of Economics, August 1979. (30) JACKSON,, E.L. The Consumption of Tobacco Products: A Descriptive Economic Analysis, United States 1900-1940. Unpublished Ph.D. dissertation, Harvard University, 1942. (31) JACKSON, E.L. Trends in the Consumption of Tobacco Products, United States, 1 500-1950. journal of Farm Economics 32(4, part 2): 881-893, November 1950. (32) KIRCHOFF, H., RIGDON, R.H. Smoking Habits of 21,612 individuals in Texas. journal of the National Cancer Institute 16(5): 1287-1304, April 1956. . - (33) LEWINE, H. Good-Bye to All That. New York: McGraw-Hill Book Co., 1970. (34) LEY, H.A., Jr. The Incidence of Smoking and Drinking Among 10,000 Examinees. Proceedings of the Life Extension Examiners 2: 57-63 1940 . , (35) LlEB, C.W. Can the Poisons in Cigarettes be Avoided? Reader's Digest 63: December 1953. # 45-47, •~.. (36) MILER, L.M., MONAHAN, J. The Facts Behind the Cigarette Controversy. Reade r's Digest 65: 1 Jul 1954 6 . - y , (37) MILLS, C.A. Tobacco Smoking: jome Hints of Its Biological Hazards. journal 46: 1165 -11 70, 1950. Ohio Medical (38) MILLS, C.A., PORTER, M.M. Tobacco Smoking Habits in an American City. journal of the National Cancer Institute 13: 1283-1297, April 1953. 47 . 0048268 TIIVIN

(39) MILWAUKEE JOUQNAL. Consoiidated Consumer Analysis. Annual, 1 947-1 969. (40) MILWAUKEE JOURNAL. Consumer Analysis of the Greater Milwaukee Market. Milwaukee Journal, 1924-1979. (41) NICHOLLS, W.H. Price Policies in the Cigarette Industry. Nashville, Tennessee, Vanderbilt University Press, 1951. (42) NORR, R. Cancer by the Carton. Reader+s Digest 61: 7-8, December 1952. (43 ) PEARL, R. Tobacco Smoking and Longevity. Science 87(2253): 216-217, March 4, 1938. (44) PORTER, E.O. The Cigarette in the United States. Southwestern Social Science Quarterly 28: 64-75, June 1947. (45) PRINTERS' INK. Women and Cigarettes. Printer's .ink 158(7): 25-27, February 18, 1932. (46) PRINTERS' tNK. Blow Some More My Way. Printer's Ink 159(2): 20, April 14, 1932. (47) ROGOT, E. . Smoking and Mortality among U.S. Veterans. Journal of Chronic Diseases 27: 189-203, 1974. (48) ROYAL COLLEGE OF PHYSICIANS OF LONDON. Smoking or Health. Kent, Eng•land: Pitman Medical Publishing Co., Ltd., 1977. (49) SALES MANAGEMENT. How. Critical are Men of Women who Smoke and Drink? 41 (6): 36, September 15, 1937. (50) TENNANT, R.B. The American Cigarette Industry. New Haven, Connecticut, Yale University ~ Press, 1950. (51) TOBACCO RESEARCH COUNCIL. Statistics of Smoking in the United Kingdom. G.F. Todd ~ (Editor). Research Paper No. 1, 1972, and ' Supplements 1973-1975- (52) U.S. DEPARTMENT OF AGRICULTURE, ECONOMIC RESEARCH SERVICE. Tobacco Situation, various issues. (53) U.S. DEPARTMENT OF COMMERCE, BUREAU OF THE CENSUS. Historical Statistics .of the United States, Colonial Times to the Present, 1975. (54) U.S. DEPARTMENT OF HEALTH, EDUCATION, AND ; WELFARE, PUBLIC HEALTH SERVICE. Smoking and Health, Report of the Advisory Committee : to the Surgeon General of the Public Health Service, Public Health Service Publication No. 1103, 1964. 48 TIMN 0048269

t : (55) U.S. DEPARTMENT OF HEALTH, EDUCATION, AND ViELFARE, PUBLIC HEALTH SERVICE, NATIONAL CENTER FOR HEALTH STATISTICS. Cigarette Smoking Status--June 1966, August 1967, and August 1968. Monthly Vital Statistics Report 18(9): 1-4, Supplement, December 5, 1969. (56) U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, PUBLIC HEALTH SERVICE, NATIONAL CENTER FOR HEALTH STATISTICS. Changes in Cigarette Smoking Habits 8etween 1955 and 1966. Vital and Health 5tatistics, Series 10, Number 59, April 1970. (57) U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, PUBLIC HEALTH SERVICE, NATIONAL ~CENTER FOR HEALTH STATISTICS. Changes in Cigarette Consumption 3etween June 1966 and August 1968. Monthly Vital Statistics Report 19(9): 1-4, Supplement, December 16, 1970. (58) U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, PUBLIC HEALTH SERVICE, NATIONAL CENTER FOR HEALTH STATISTICS. Cigarette Smoking: United States, 1970. Monthly Vital Statistics Report 21 (3): 1- 8 ; , i Supplement, June 2, 1972. . > (59) U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, PUBLIC HEALTH SERVICE, NATIONAL CENTER Estimates FOR H from EA th LTH STATISTICS. Current e Health Interview Survey, United - States - 1976. Vital and Health Statistics, 1977. Series 10, Number 119, November (60) U.S. DEPARTMENT OF HEALTH, EDUCATION, AND ; ; WELFARE, PUBLIC HEALTH SERVICE, NATIONAL i .~ CENTER FOR HEALTH STATISTICS. Current r Estimates from the Health Interview Survey, 1974. Vital and Health 10, Number 121, December (61 ) U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, 'PUBLIC HEALTH SERVICE, NATIONAL CENTER FOR HEALTH STATISTICS. Changes in Cigarette Smoking and Current Smoking Practices Among Adults: United States, 1978. Advance Data From Vital and Health Statistics, No. 52, September 19, 1979. Statistics, Series 1978. 49 United States TIMN 0048270

(62) U.S. DEPARTMENT OF HEATLH, EDUCATION, AND WELFARE, PUBLIC HEALTH SERVICE, NATIONAL CLEARINGHOUSE f='OR SMOKING AND HEALTH. Use of Tobacco, P,actices, ALtitudes, Knowledge, and 8eliefs, Uoited States, Fall 1964 and Spring 1966. July 1969. (63) U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, PUBLIC HEALTH SERVICE, AND ADULT HEALTH. NATIONAL CLEARINGHOUSE FOR SMOKING Use of Tobacco, 1-?70. June 1973. (64) U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, PUBLt{= HEALTH SERVICE, NATIONAL CLEARINGHOUSE FOR SMOKING AND HEALTH. (65) U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, PUBLIr HEALTH SERVICE, NATIONAL CLEARINGHOUSE F3R SMOKING AND HEALTH. Adult 'Use of Tobacco 1975. 1976. (66) U.S. FEDERAL TRAOE COMMISSION. Reports of "Tarl and Nicotine Content of the Smoke of Varieties of Cigarettes, 1967-1978. (67) WARNER, K.E. Possible increases in the Underreporting •_If Cigarette Consumption. journai of the American Statistical Association 73(362): 314-318, June 1978. (68) WESSEL, C.A. Th= First Sixty Billions are the Hardest for the Cigarette industry. Printer's Ink 120(5): 3-6, 137-146, January 31. 1924. (69) WHITTEN, I.T. Brand Performance in the Cigarette Industey and the Advantage of Early Entry, 1913-74. Staff Report to the U.S. Federal Trade Commission, June 1979. Y TIMN 00452 71 50

PART if: BI(JMEDICAL ASPECTS OF SMOKING . a a

CtGARETrE SMOKING AND MORTALITY AMONG WOMEN ( NTRODUCTION A1VD BACKGROUND Cigarette smoking has been cited as the single most important environmental factor contributing to premature mortality in the United States (17). A great many epidemiological studies support this statement. The emphasis, in general, has been to study males rather than females. Perhaps the main reason for this discrepancy is that, in the past, relatively few women smoked whereas smoking was common among men. The upward trend in lung cancer death rates in males observed in the 1950s by Dorn and others stimulated epidemiologic studies of smoking and health, especially among males (2,3). According to the 1979 Surgeon General's 'Report: It is important that attention be called specifically to the mortality that females experience as a result of cigarette smoking. There has been an increase in- smoking among teenage girls over the past 10 years.' At present, the percentages of teenage boys smoking and teenage girls smoking are nearly identical. For some ages,- there are more teenage girl smokers than boy smokers. Over the past 10 years, there has been a gradual reduction in the percentage of the adult population that is smoking. Men have quit in greater numbers than women. There has been only a modest drop in the percentage of women who are smoking. In Canada and several European countries, smoking is decreasing among men but increasing among women. . 71 The present report reviews some of the more important prospective epidemiological studies on cigarette smoking and mortality among women. fYIORTALlTY TRENDS As background, this section reviews mortality levels by sex and color in the United States, by examining recent trends in overall mortality, and in three causes of death which have been strongly linked to cigarette smoking--ischemic heart disease, lung cancer and the combined category of bronchitis, emphysema and asthma.* These trends are displayed in Figures 1 through 4. *Although asthma may be included in the category, chronic obstructive lung disease, it is not causally related to smoking. 53 0 TIMN 0048273

FIGURE 4.-,>,gaadjtuted death rates• for brohahitis, iinphysema, and asthma- by color and mUnited Stata` 1950-1977 _ : white MsIK~ Nttnwhite Mata ' ~ , . . . . _ .. ` .. .. . /~~ . . ~ • . _ . . ._. _ . . .. . \ . ' ' NOTLh 1tf Flma1K •.. • rVhit! FErtulef . 20 10 0 2 1950 1995 I 8th Rev t960 1965 7th R'w. ' Adiustld by the direct mlthod t0 th! U.S. poputation, 194Q "ICO 8th and 7th Rw.Nos.241,501,502 527,1 and 8th Re.. Not. 490;d93,549,3. • SOURCE. Oata from the National Cent.r for Health Stahtacs. 1970 30 20 10 5 Z 1975 8th Rev. ~ TIMN 0048277 57

_ ----_-__^~ C ~ Y C ~ w 3 -- ~ w C .. ~ a. -~ w w ... ~ . 96 ~ O ~. • tZ (16 > K v T. ~ ... ~ y ta e # ~. ~ .~.q O. A 1L G I .O N w /.. O C N v C N V y ' 'n - at F ~ ~. ~4.w •Vf "C !~' •I N a -a , •y..'.'.. Go ~•w V y N ~ A ~ 0 CIC b d ~ ~ 0 O..C: N Tv._.. 1 c 0.' 3 • • Q . . . r .a, . .n ... _ _G ..... :.~a.N.,w •~ " . . ~: . . _ . .:... . _ .. 3}..j^,r.4:. _ -_.. .. . - . ,~ , ~ . .. . . . .. ~''S`. .:'r?' . yn . - _ .~ v . . .~_ N } ~ Yf ` ` LS w Y Q .R R C L ~ .. • IL •~ Y, M AC dC w1 ~ o ~ N a ~n a o v " K ^ ~ C . ~ ~ e,eE .~. v _ ~ ~ m S . .t. •. '.s N a Y f~ ~ Y • N 1r1 h I6 y y 1 ~ W. C. ~ p ~ C. r: N r .~ .~ o 0 V . C C6 M ~ ~ y A ~ n C w i. b 6t C1 ^ o w w 1 y + e r N y e) "P ~. 4 %a 1fl {'A ~ Y ~ V~ ~ O M Y M ~ C • w w C Y O 2,0 O ~. o Y r 3 O o ~ o M = V o ~ F ~ ~ E w.~ ~ ~ r N e V r O a ~ w ~ Y N .. w 9 r. Y Y C O O • Ir Y w Z ~ ~ = v 9 ~ M V ..-. Y ~ V w ~a s

........,,.-..~ 11,858 deaths had occurred and there were 1,269,382 person-years of observation. • For women, 'however, the main body of published data is based on 4 years of follow-up. .The Rritish Doctors Study (2) ' - In 1951, the Rritisit; !Medicai- Associatiort. forwarded to- all British doctors a questionnaire-'about their smoking• habits. A total of 34,4n0 men * and" 45,207 women responded. With few exceptions, all men who repiied in 1951 have been followed for 2(t years. Further inquirtes 'about changes in tobacco use and some additional demographic characteristics of the men were made in 10571, 1 Q6F, ind. 1172. • More than 1 n,000 deaths have occurred In this popuiation -. during. the past 20 years. For women, pubiished data :are available for 11 years of follow-up, and unpublished data are available for ?2 years ' of foiiow-up. The Framingharn Heart Study (10) • The Framingham Studv began in 1948 with a cohort of 2,33F white men and ?,R73 white women who were age 29 to 62 at . the beginning of the study and were residents of FraminRham, Massachusetts. Persons were selected by a*sampie of households plus enlistment of '-voiunteers. These individuals were recalled and examined every.'7 years thereafter. The routine cardiovascular examination consisted of a medical history, physical examination, blood chertistries, body measurements, vitai ' capacity, chest x-ray and a 12-iead etectrocardiogram. Mortatitv and morbidity were documented in detaif, from the routine biennial examination, hospital records, death certificates, physician records and the next- o f-kin. Information on smok.ing was obtained at the first examination (and at several thereafter). A series of monographs and over 2nn articles on the Framingham Study' have now become part of the scientific literature. nata on the reiationship of cigarette smoking to cardiovascular morbidity and mortality, for both men and women, have been reported in the Framingham literature, hut the longest reported follow-up period has been 1 R years with relatively few deaths having occurred by then, especially among the women (11). Data given below are based on a

a OVERALL MORTALITY FOR FEMALES - CIGARETTE SMOKERS VERSUS NON-SMOKERS Mortality Ratios In this report the mortality ratio is the basic means of comparing cigarette smokers with nonsmokers. It is usually obtained by dividing a"death rate" (or other mortality measure) for a classification of smokers by the "death rateM (or other mortality measure) of a comparable group . of nonsmokers. The "death rate" may differ markedly from one study to another. In some studies it is calculated by means of person-years and is a I-year measure; In others ; it is a probablity measure; it may be a 5-year, 10-year or, as in the Framingham Study, a: 26-year measure. Differences in mortality ratios may arise because of these factors. Because of the arithmetic nature of this ratio, there is a tendency for lower ratios to result with higher underlying levels of mortality. For example,, with an underlying mortality level of 10 percent per year for nonsmokers, the mortality ratio for a group of smokers can at most be .10 if all the smokers died within the year. With a mortal ity level of 50 percent . for nonsmokers, the maximum possible ratio is 2. Since "death rates" increase with age, there is a tendency for the mortality ratios to decline with age, since its range' Is restricted. For simplicity, however, mortaiity ratios are used throughout this review; it is recognized that these ratios are not strictly comparable from one study to another nor from one age group to another. Amount Smoked and Age Overall mortality ratios by amount smoked and age are presented for several of the studies in Tables 2-7. Except for the Swedish study (Table 3), age-adjusted ratios were calculated for each level of smoking in each study. Adjustment was by the direct method, using as standard the age distributrion of all women in the particular study. For the Swedish study the age-adjusted values were taken directly from the report. Mortality ratios shown in. Table 2 are considered especially important since they are derived from the study with the largest survivorship experience. Mortality ratios 63

TABIE 3.-Mortality ratios for female cigarette smokers by. number of cigarette smoked per'd'ay and age. Females in the Swedish study.' Number of =. cigarettes per day - 1R-39~ Are 40-49 50-59 6t1-69 Total, iF-6a Age-adjusted . . Non-smokers 1.0 1.0 i.n t- 7 1.0 " 1.6 1.t .9 1.0 8-t5 _2.3 • 2.2 t.7 1.5 t6+ 4.5 2.2 IeS 2.2~ 2.0 ~ . -~ - -• - Ai l Snwkers-..------ :t.8. _ ....:..i.9..... t>3 -- 1.1 1.?. ..-.: ---• -- - - - _ SOllRCE: Cederiof. R.. et al !1{. TIMN 0048283 65

TABLE 5.-Mortatity rati'os for female cigarette- smokers by number of cigarettes smoked per day and age.. Females in the Framingham Heart Study.. Number of cigarettes. per day Nonsmokers <20 20 29-44 1.00 1.42 Age 45-54 i.n0 1.21 1.4F ` • 55-62 1.00 1.07 1.13 Total,. 29-62 Age-Adjusted // 1'.n0 1.30 1.SZ .LJ 1. ~ i:72--- - - a --- '=- ' Afii 4malc rs t .E2 t s2 I.A3 1/ Adjusted by the direct method using as standard the age distribution of all women. ' Not shown - less than 5 expected deaths. SOURCE: Framingham Heart Study, unpublished data (1M). TIMN 0048284 67

TABLE 6.-Juortaiity ratios for female cigarette smokers by number of cigarettes smoked per day and age. British females. x Number of cigarettes Age per day 45-54 55-64 A5-74 Total, 45-74 Age-adjusted i/ Nonsmokers 1.00 1.00 1.00 1.00 <20 1.49 1.09 .79 i.nA 20+ 1.85 1.51 1.55 1 .60 All Smokers 1.66 1.25 .9R /.25 1/ Adjusted by the direct method using as standard the age distribution of all women. SOURCE: Rr'itish-iVorwegian Migrant Study, unpublished data (10). 68 21, TI~N pp48285

- - -------- --- s--.~-.~ - ~ - -- ~ ,~ - - -- - =-~=~ ----~_ ----~=~ ~ -----"-^-- '~ ',~- =-= TABLE-I.-Mortal'ity rattos for female cigarette smokers by numbe?-of'cigarettes smoked per day and age. NowKegian females. Number of ci $afettes.' . - Age . • per day-, 45-64- 65-74 Total, 45-74 Age-adjusted 1/ Nonsmokers ,1.00 .1.A0 <20 1054 t.n7 1.33 20+ .89 A11 en.nkers 1_A4•. -j.•0'_- 1.25 1/ Adjusted• by the direct method using as •standard the age di - - - SOURCE:''British-Norwegian~Migrant Study, unpublished data {tA). TIMN 0048286 b9

generally rose with the amcunt smoked for each age group except for the 75 to 84 age group. The age-ratios were .97 for the 1-to-9-cigarettes-p-,r day group, 1.19 for the 10- to-19 per day group, 1.45 for the 20-39 group, and 1.63 for the 40-plus group. For all cigarette smokers the age- adjusted mortality ratio was 1.26. By age group, mortality ratios were 1.12 for the 35 -to-44 age group, 1.31 for the 45-to-54 age group, 1.27 for the 55-to-65 group, 1.31 for the 65-to-74 group and 1.14 for the 75-to-84 age groups. ~---- Data from the Swedisii study (Table 3) appear to be reasonab ly consi stent with tha ACS data in Tab le 2. The 1- to-7-cigarettes-per-day grou;: had an age-adjusted mortality ratio of 1.0 (compared with :37 for the 1-to-9 group above) and 2.0 for th 16-plus group (compared with 1.63 for the 40-plus group above). For three of the four age: groups, the mortality ratios were dire=tiy associated with level of smoking. By age group, the highest mortality ratios were observed for the two youngest age groups and the lowest for the two oldest groups. The overall ratio for all cigarette smokers was 1.2. For the other studies (Table 4-7) mortality patterns were general iy similar in tha?, mortal ity ratios tended to be highest with heaviest smoking and tended to be lowest at the oldest ages. For the Japanese study and the British Doctors Study, mortality ratios by amount sm•_*ed and age were not reported. However, an overall age-adju-ud mortality ratio for female cigarette smokers was reported in the Japanese study, while in the British Doctors Study this ratio was obtained from unpublished data based on 22 years of follow-up (Table 8). We list these along with th_ overall ratios for the other studies: Study Total mortality ratio age-adjusted American Cancer Sociei.y 1.26 Swedish 1.20 Canadian 1.31 Japanese 1.28 British Doctors 1.23 Framingham 1.43 British Migrants 1.25 Norwegian Migrants 1.28 . : i i : i i i i : i : i ;" i ~ ~ ti. i r : : r : ~ a r< TIMN 0048287 70

TABLE 8.-Mortatity ratios for female cigarette smokers by number of cigarettes smoked per day. Females in the British Doctors Study. Number of cigarettes per day Total, "Age-adjusted I/ Nonsmokers I - 14 15-24 25+ I-.00 0.44 I.54 1.66 Ali Smokers 1.23 ' t/ Rased on annual death rates standardized for age. SOURCE: British Doctors Study, unpublished data (2). TIMN 0048288

Ait ratios here are greater than unity. The largest ratio is 1.43 for Framin;iham. The other seven ratios are ciose to one another, ran:;inA -from 1..2 for the 5wedish study to 1.31 for the Canadian study. . Duration of Smoking trtverait mortality 'ratios for women increased with duration of the smoking habit based on. data from the Canadian and Swedish stud-ies- (1,5). Among Canadian women who smoked for K1 or more years the mortality ratio, adjusted for age, was 1.37 compared to a ratio of I.(!R for women smoking less • than Km years. In the Swedish study an excess risk was found for women smoking . 30 -_1r. more years (1.4). For" those smoking less than 3n years the ratio was W. Age i3eRan Smoking Table o shows mortality ratios for women who were 45 to 54 by number of cigarettes smoked per day and 'age began smoking (6). Except for. the. light. cigarette smokers ( i-to- 3-per-day), those taking lrp . the..hahit at_ ages 14 to ?4 had higher mortality ratios than those who started smoking at older ages. , ... Mortality 'data for women, smokers, according to age started, are also available from the Swedish study (1 ); age- adjusted ratios were repo.,ted as 1.7, 1.6, and 1.1 for age stirted less than 17, 17 to IA, and IQ pius, respectiveiv. t nha iat ion

TABLE 10.-Age-adjusted mor~ality ratios of female cigarette smoker-,, by number of cigarettes smoked per day a,id degree of inhalation. Subjects aged 45•54 at start of study. 25-State Study. Number• of Degree of Inhalation of smoke cigarettes per day 10 - 19 20 • -' 39 - 40+ None-Slight Moderate-Deep 0.85 1.04 1.27 1.17 . 1.41 1.58 se 2.14 SOURCE: Hanmond, E.C. {F); ` ": *• Ratio not shown--iess than In expected deaths. ~~ ---~ .~-.~--

_ ..,,,_.._ ............... TABLE 11.-Age-adjusted mor°tality ratios of female cigarette smokers, by number of cigarettes smoked per day and degree of inhalation and age. 25-State Study. Degree ' of Age Inhalation 35-44 45-54 ,.•55-F4 65-74 7$-84 Nonsmokers None Slight Moderate. Deep 1.0A s« 1.22 - 1.05 1.40 I.AO 1.01 1.21 1.30 t.78 1.00 " 1.1I 1.28 1.32 1.64 1.00 ' 1.12 1:26: 1.41 s+ 1.OA• 0.96 y 1o21 ss sa SCIJRCE: Hammond F.C. (6). . s• Ratio not shown --less than 10 expected deaths. TI1VjN 0048292

Mortality data for female cigarette smokers according to inhalation are also aviilabte from the Swedish study (1); age-adjusted ratios were reported as 1.1, 1.2, and 1.6 for the no inhaiation, light inha_ation, and deep inhalation groups, respectively. "Tar" and Nicotine Content of Cigarettes The relationship between 3verall mortality and the "tar" and nicotine content of cigare :te smoke was recently examined by Hammond, et al. (7). In this study, "tar" and nicotine levels (T/N) were defined as foliows: "High" T/N,' 25.8 to 35.7 mg "tar" and 2.0 to 2.7 mg nicotine; "Medium" TJN, 17.6 to 25.7 mg "tar" ind 1.2 to 1.9 mg nicotine; "L,owp T/N, less than 17.6 mg "t?r" and less than 1.2 mg nicotine. -- Table 12 shows the overall mortality ratios of male and female smokers by these 'tarp and nicotine levels. ' In 'this instance, the mortality ratio of the "high" T/N smokers was represented. as 1.00 to Hustrate the reduction In ' overal l mortality that occured wit;i lower T/N cigarettes. There was a small reduction in the r'sk of dying with the use of lower T/N cigarettes. The morL=Jity ratio was reduced to 0.91 for the "medium" T/N smokers and was further reduced to 0.84 for the "low" T/N smokers. The mortality ratios were lower for women than for men. In a separate analy-,is, a comparison was also made between the mortality ratios of "tow" T/N smokers and non- smokers. These data ar e presented in Table 13. The mortality ratio of the "low" T/N group was designated as 1.00. Nonsmokers had o:erall mortality ratios •that were considerably less than those of "low" T/N smokers. The combined data from Tables 12 and 13 are shown in Table 14 where mortality tatios were calculated using non- smokers as the reference. Combining these data from two separate analyses that are not exactly comparable results in figures that are only approximate. Hammond also compared death rates of smokers of relatively few (I to 9) "hi;h" T/N cigarettes with those of smokers who smoked relatively large numbers (20 to 39) of _" low" T/N c igarettes (17). The death rates of these two groups were very similar.

TABLE 12.-Adjusted mortality ratios for males and females, by "tar" and nicotine content of cigarettes usualiy smoked. Mortality Ratios Sax "HiBh" T/N "Medium" "Low" T/N TfN Males 1.00 0.94 0.85 Females 1.00 0.88 . 0.83 Totai 1.00 0.91 0.84 SOURCE: Hamrond, E.C. (7). TIMN 0048294

TABLE 13.-Adjusted mortality ratios, for mates and females smok'ing low "tarR and nicotine cigarettes and subjects who never smoked reauiirty. Sex •Lo-ru- T/N' Mortality ratios Nonsmokers

TABLE 14.-Orerall mortality ratios of ci=arette smokers compaied to nonsnwkers;`by sex and by Itar• and nicotine, content of cl8arettes usuaFly smoked. Sex Non- . Smokers Males 1.00 Females 1.00 , 'Lowe Medlums TfN T/N 1.66 a}tigh. TIN ..1.85 1.96 1.37 1.45 1.52 1.64 1.65 1.80 TIMN 0048296.

COMM ENTS Mortality ratios for women who smoke cigarettes ranged from 1.2 in the Swediso study to 1.43 in the Framingham study. As with' men, mr-rtality ratios for women who smoke c igarettes vary- directly with amount smoked, depth of inhalation, ntar" and nicotine content of the cigarette inif duration of smoking, and varied, inversely with the age when smoking was started. In attempting to stsidy cigarette smoking and mortality among women, a major d ifficulty is the lack of large-scale epidemiological studies addressed. specifically to female populations. The main f1hidings of this review depend heavily on one study, that of the American Cancer Society. For the other studies reviewed he-,e, the numbers of women--and of deaths among them--are often too sparse to permit meaningful statistical anai yses. Thus, for example, little can be said about the survivorship experience of women who ive __~__v ' up cigarette smoking. We strongly recommend, where possible, extending the length of follow-up of women who are already enrolled in these prospe•;tive studies. It is also hightyr--~- - recommended that new studies be conducted that are specifically addressed to wDmen and smoking-related mortality. SUMMARY I. The mortality ratio for women who smoke cigarettes is' about 1.2 or 1.3. 2. Mortality ratios far women increase with the amount smoked. In the largest pnospective study the mortality ratio was 1.63 for the two-pack-a-day smoker as compared to nonsmokers. 3. Mortality ratios are generally proportional to the duration of cigarette smokiig; the longer a woman smokes, the greater the excess risk of dying. 4. Mortality ratios t;nd to be higher for those women who begin smoking at a yo!-ng age as compared to those who begin smoking later. S. Mortality ratios ire higher for those women who report they inhale smoke than for those who do not inhale. 6. Mortality ratios `or' women tend to increase with 'the tar and nicotine content of the cigarette. 7. Mortality ratios tor female smokers are somewhat less than for male smokers. This may reflect differences in 80

^ w- - - r::~ =:.. r:.. .r , .::.. ~<= ~------=--~--: :~ ' . . - -- - - - - - - - - -- - -------- - - ------- ------------- - exposure - to cigarette smoke, such as starting smoking later, smoking cigarettes with lower "tar" and nicotine content, and smoking fewer cigarettes. per day than men. 8. Women demonstrate the same , dose-response relationships with cigarette smoking as men. An increase in mortality occurs with an increase in number of cigarettes smoked per day, an earlier age of beginning cigarette smoking, a longer duration of smoking, inhalation of. cigarette smoke, and a_ higher tar and nicotine content of the cigarette. Women who have smoking characteristics similar to men may experience mortality rates similar to men. TIMN 0048298 SZ,

CIGARETTE SMOKING AND MORTALITY AMONG WOMEN: REFERENCES (t )" BEST, E.W.R. - A Canadian study of smoking and health. Depariment of National Health and Wei fare, Epidemiology ' Division, Health Services Branch, Biostati mics Division, Research and- Statistics Directorate, 196•6, 137 pp. (2) CEDERLOF, R., FRIB::RG, L., HRUBEC, Z., LORICH, U. The relationship of smoking and some social covariables to ,nortality and cancer morbidity. A ten year fallow-up in •a probability sample of 55,000 Swedish -;ubjects age *18 to 69. Part I . and 11. S=ockholm, Sweden, The Karolinska Institute, Departnient of Environmental Hygiene;. 1975, 201 pp. (3) DOLL, R., GRAY, R., PETO, R. Mortality in rela- tian to Smoking: Observations on female doc- tors. (Unpublished data manuscript, in prepara- tion). (4) DORN, H.F. The Increase in cancer of the lung. Industriai Medicine and Surgery 23(6): 253-257 June 1954. (5) DORN, H.F. The r-aationship of cancer of the lung and the use of tobacco. The American Statistician (American Statisti.;al Association) 8(5): 7-13, December 1954. (6) HAMMOND; - E.C. Sonoking In relation to the death rates of one i-i-iilion men and women. In: (7) Haenszel, . W. (Editor). Epidemiological Approaches to ths Study of Cancer and other Chronic Diseases_ National Cancer Institute Monograph 19. U.S. Department of Health, Education, and Welfare, U.S. Public Health Service, National Cancer lnstitute, • January 1966, pp. 127-204. HAMMOND, E.C., GAr=;FINKEL, L., SEIDMAN, H., LEW, E.A. wTar" and nicotine content of cigarette smoke in relation to death rates. Environmental Research 12(3): 263-274, December 1976.

(15) REID, D.D, CONFiM.D, j., MARKUSH, R.E., et al. Studies of dise=.se among migrants and native population in G reat Britain, Norway, and the United States. li . Prevalence of Cardiorespira- tory symptoms atg iong migrants and native born in United States. National Cancer Institute Monograph 190. U.S. Department of Health, Education and Weifare, U.S. r~ublic Health Service, National Prevalence Cancer Institute, Monograph 19: 321 - 346, 1966. (16) ROGOT, E. Caediorespiratory disease mortality among British NcrwegiYn migrants to the United States. American journal of Epidemiology 108(3): 181-191, 1978. (17) U.S. PUBLIC HEALTH SERVICE. Smoking and Health. A Report of the -iurgeon General. U.S. Department of -Health, Educa;,ion, and Welfare, Public Health Service, Office •)f the Assistant Secretary for Health, Office osi Smoking and Health. DHEW Publication No. (Pi-?5) 79-50066, 1979.

TABLE 1.-Days lost from work per year due to Illness and inJury, per currently employed person 17 years old and older, by smoking status, sex an age: United States, 1965 and 1977. Totai9l Fema t'e 17+3 T 7-44 45-64--- hfal e 17+3 T7-44---- 45-64 Femate- - 20+3 20-44--- 45-64 :_ Present Smoker Former Smoker 'eroent.of work loss days 1965 5.6 6.6 6.7 5.5 6.6 6.0 6.0 6.7. 7.7 5.7 5.9 6.8 4.1 4.7 3.6 7.8 7.9 9.8 1977 6.0 6.6 5.4 6.1 6.8 5.4 6.4 6.5 5.92 5.3 5.9 6.1 5.1 •6.0 - 5.S 5.6 5.9 6.2 Tinatudes-unknown smoking status. ZFigure does not meet standards of 3lnoiudes ages 65 and over. 4.2 4.4 3.9

same. This would tend to reduce the number of 1'excess" days among women attributable to smoking. There has been a slight decrease in work-loss among males who never smoked. Former 'smokers reported fewer work-loss days in 1977 than in 1965. Although the difference in work-loss days between 1965 and 1977 is small, it could be attributed to the assumption that in recent years the former smoker groups have a greater proportion of people who stopped smoking for preventive reasons, that is, before they had experienced serious health consequences. Futther study is needed to determine the association between nexcesst' days lost from work by smokers and specific diseases. Such an analysis would help explain the economic impact of smoking in the work place. LIMITATION OF ACTIVITY The Health Interview Survey also regularly collects data on the long-term impact of chronic illness.' Respondents were asked if chronic illness Iimited their activities (3). Estimates of the percent of the population with ' limitation of activity by cigarette smoking status are shown in Table 2 for 1965 and 1977. Detailed interpretation of trend data is difficult; however, there appears to be a relationship between smoking and the impact of chronic illness. In general, the 1977 data• indicate that women under 65 who have ever smoked are more likely to have a limitation of activity than those who never smoked. There are no marked differences between current and former smokers. Among elderly women in 1977, there were no differences in limitations of activity by smoking status. CIGARETTE SMOKING AND OCCUPATION* The Health Interview Survey provides a considerable. data base on cigarette smoking behavior. and occupational status. The data are available from a national probability sample of about - 40,000 households for the years 1965, 1966, 1970, 1974, 1976, 1977, 1978, and 1979. However, only minimai analysis - TIMN 0048304 *See: It Interaction Between Smoking and Occupational Exposures" in this Report.

Total ~~ P'esent imoker Former Smoker Percent with limitation 1965 65---- - Male Never Smoked 17+ - 17.3 15.3 23.0 17 7 17-44---- 7.3 r.7 8 0 . 45-64---- 20.0 20 9 . 6.2 65+ . 22.1 15 7 -.----- 53.7 5:.7 56.3 . 52.9 1977 lincludes known smoking status.. SOURCE: Health•Interview Survey, National Center for Health Statistics.

has been conducted on this potentially valuable data base (4). This briefn section presents data on smoking patterns for only two of these periods--19700 and 1976. Researchers are encouraged to investigate these date more fully through the purchase of : public use data tapes (2). , The importance of this data base increases as new evidence becomes available on the increased health risks experienced by smokers in certain occupations. The problems of' relatively small sample. sizes in high-risk occupations can be partially overcome by combining several years.. of the HIS data tapes. Tabies _ 3 and 4 show• smoking characteristics of broad occupational groups--i.e., white '.collar, blue collar,. service and farm workers--for 1970 'and 1976, respectively. Service and blue collar workers, both women and men, are more likely to smoke than are white collar-: and farm workers, but the differences are much less among female workers. In 1970, there were virtually no differences among female white collar, blue collar, and service workers; more recently, however, there has been a slight increase in smoking among, the latter two groups. Caution should be used in drawing conclusions from these data based on differences of only a few percentage points since such differences can be well within sampling error. White collar workers who smoke tend to be heavier smokers than other types of workers, and this pattern is more marked among female white collar workers. The proportions of cigarette smokers by more detailed occupational -classes are shown in Tables 5 and 6 for 1970 and 1976. Within three of four subgroups of white collar workers--professionals, managers, and sales people--the proportion of smokers among women is the same as for men in the same occupational group. This also appears to be true for laborers, who show the highest levels of smoking among both women and men. ' TIMN 0048306 SUMMARY The 1979 Report of the Surgeon General summarized the information on smoking and morbidity as follows: 1. In general, female current cigarette smokers report more acute and chronic conditions including chronic bronchitis and/or emphysema, chronic sinusitis, peptic ulcer disease, and arteriosclerotic heart disease, than women who never smoked. 89

0 YJ M.-1~C P ~0 C • T T T f: 1 r O O f f • t • .~sveNrn .~ N M .~ h M T R. T T T N sf~~C • CO v. V r r r Y E O ~ Q v 1 M N..10M %0 NO ac N1Cr O I N » Ioto_ r~.r ~.~C.~1~ O u ~ . T T.=i T T T NNNI~I% N w n Y 0 w a E w w eN CG= Coo C C C C G C w w Y Y G C~ C C C C C C C C C C ~ ~. O s.r CC•^CCC 0 E M C ~. Y • • w.Y e GO~~ GCT Q.! 10~NCh ~ .~T~GeI~ ~6 T T T T T T rv TM~ R~ w V V Y ~ ' w V V e w O i T10 N02 01 .. Y T t N ~ y T T r C ~ f/AOINT 6C N N K N N N . t v C C Y w . O M Y ~ QS Q V Y nae N M O T f O u o v Y > O n E : f C.~ C O~ Of Of 0:-e 0: -W Z O G- • M M M M f M N N T N h T N Y u. ~ w O . C V 0 cCoCCo 6 C C C C O ca^^CC ~.. O C O G O C G G C C C O G O ^ ^ ^ ' v w 3.. Y .a » Y ~ ~ 9 s o Y .. ~. E w z w ~ y y O C .. w 3 > C w .~ • > > Y,. Y C C E e C O C C C C w w 7 3 Y o ro » v O Y . V 9 n . > > V ~ u r:: ::r.- - ¢ ~ ::....................._..............._...........::~:. :................. cu 0 ".a - (% 0 N _ . ~r.-~ -----=--

TI18E.F 6,-Estlmoet of the perOenRafe of current, refultr flairette smokers, adults ias; 20 years and over, according to labor force status and occupation and sex, U.S., 1976, t Total Currently employed Whito collar total Professional technical and kindred managers ot aaministrators -except farm Sales wofkers Clerical dckindred woikers Blue collar total Craftsman & kindred workers •Operatives and kindred workers ' Laborer, except farm Service Farm Unemployed Usual aetivity-homemaker's Female Male Total 20+ 70-44 45-64 Total 20+ 20-44 45-64 32.0 36.9 34.8 41.9 47.6 41.3 35.9 37.0 36.1 43.4 46.8 39.7 34.3 33.8 • 36.9 36.6 38.6 35.3 29.1 28.6 32.7 30.0 31.1 29.9 41.6 42.7 40.8 410 46.4 36.1 38.1 37.0 42.6 39.9 42.6 3r•.0 34.8 34.7 36.0 40.4 40.1 44.2 39.0 43.7 33.6 50.4 54.1 44.3 40.5 46.9 35.6 48.0 52.1 . 41.6 37.6 42.5 31.2 52.3 55.3 46.2 56.3 52.6 . . 53.7 56.9 51.7 39.0 42.8 37.7 47.2 51.1 44.8 31.3 51.0 • 36.q 45.4 35.0 40.0 41.0 39.9 56.8 59.9 53.8 29.0 37.1 32.2 NA NA NA NOTE: Unknown If ever smoked excluded from calculation. •Fisure does not meet standards of reliability or peeislon. SOURCE: Health Interview Survey, National Center for Health Statistics. .e .... ...... ... .... .... .~L'.. ... .. ._. ..... ...... ... .... _.

SMOKING AND CARDIOVASCULAR DISEASE tN WOMEN f NTRODUCTfON Vrhire the mortality and morbi,lity rates of coronary heart dFsease (acute myocardial infarction and chronic ischemic heart disease) (CHD) are lower for women than men, CHD still represents the major cause of death among women in the U.S. In 1976, the United St-.tes recorded 284,055 female deaths as attributable to this cause (Table 2). The difference in mortality rates between the sexes is more marked for acute myocardial Infarction, with males of all ages experiencing 189 deaths and females 111 deaths per 100,000 (Table 1). Obserded differences by sex in susceptibility to coronary hisart disease are not fully understood but appear to be aftiected by multiple specific-risk factors within any demographic group. McGill and Stern have recently provided an extensive review of sex differences in -wsceptibility to atherosclerosis in• humans and in experimental animals, including an analysis of factors known to predispcse to atherosclerosis and its dependent diseases (24). MORTALITY RATES tn the United States, the Nathmal Center for Health Statistics has reported mortality rates irom acute myocardial infarction and chronic ischemic heart di°ease classified by age, sex, and race, for the years 1968 and 1976 (Tables 1, 2, 3) (32). These tables show that mort?lity rates for acute myocardial lnfarction among adults up to age 64 are highest for white men and are succeeded by progressively lower rates for other men, other women, and finall•r, white women. Mortality rates for chronic ischemic heart di-.eases vary. The rates for white men pre second to those for other men and close to those for nonwhite women; again, however, rates for white women are by far the lowest. Both :rhite and nonwhite women show consistently lower rates until extreme old age. However, the differences narrow markedly in age in comparison with those in young adulthood and middle life (Table 1). Male-to-fernale mort-.lity ratios for acute rnyocardial infarction among adults in t"eir 30s or 40s are approximately 5 to 6 for *whites and 2 to 3 for nonwhites; among adults in

TABLE 2.-Number of deaths for acut® m eocardtal Infarction and chronic {sch©mic heart dlseae for sp.cftfed age groups, by color and sex; United Stales, 1968 and 1976 (Number of deaths due to acute myocardial int-arcion are those assigned to category number 410 of the Eighth Revision of the International Classification of Di;:eases, adapled for use in the United States,adopled in 1965;and for chronic ischemic heart disease to category number 412 of this revision) Vesr and a9e Tota/ Whqe ~~~ Male Femafe . ~~~ Male Female 1976 Acute myocardial infarction Ae sqea ........................................ 319,477 197429 122A48 295,613 183.820 111,793 25•34 years .......... .................................. 890 718 172 ".. 720 598 35.44 years ............................................. 6,223 5,182 1)041 5,338 4,558 •5.54yeara..,.» ....................................... 26,405 21.361 5,044 23,479 9,407 55fi4 ye.ra ,.» ....................•..•..•........•..... 62,091 46,516 15,757 55,623 43.072 65•74 years ................ ..................... ' 93,695 61,038 32,657 66,566 57 rq4 75-84 years........... - ................................ ' 89,969 46,395 43,574 84,852 43.912 85 years acd over ....... „,,,,,,„,,,,,,,,,,,,,,,,,,, 40A68 16.132 23936 37939 15,201 7968 A11 eqes ........................................ 369.610 236,017 33,593 342.999 220,517 25•34 years ............................................. 7099 838 261 846 664 35-4 ycart .................. „.... ....»......,......» 9980 8,132 1,848 8,412 . 7,122 •5•54yeara ............................................. 36,032 29,368 6,664 32,261 26,860 5544 yean ............................................. 76.108 57.387 18.721 69,504 53,287 65•74 yeara,»................ ........................ 109,672 70.564 39.108 101.863 66,205 75$4 years ............................................. 100,312 53$38 16,474 95.613 51.436 85 years and ovee .................................... 36,135 15,711 -!0 424 34,317 14,824 All other Both Mafe seaec Frmale 23,864 13.609 10,255 122 170 120 50 780 1585 624 261 4,072 2976 1,954 972 13,`,51 5r68 3,444 2,024 29$62 7,129 4,034 3,035 40_940 5.117 2,483 2,634 22,738 2,129 931 1,198 122,482 26,611 15,500 11.111 182 253 174 1,290 1,563 1,010 5,401 3.771 2,508 16,217 6,E84 4,100 35,658 7,809 4,359 44,177 4,699 2.402 19,493 1,818 887 79 558 1?63 2.`.Q4- 3,450 2.297 931 1976 Chronic tschemic heart disease Ae pea ............... ...».... ............. » 322,382 160,375 1`2A07 289572 143,372 146,200 25•34 years ..„ ....................»,................., 502 381 121 332 266 35-44 yean..» ................. ................. ».,,,, 2,937 2.273 664 2,137 1,734 4534yearn......... ,,,,.,»....... ,...»»........ ».. 13,649 10,391 3.258 10,593 8.426 55-64 years...... .... »,,,,,,,,,,,,,,,,,,,,,,,34,765 24,525 1.1240 28929 20996 65-74 yeara,,,»,,,,,,,,,,,,,,,,,,,,,,,,,,,,,69.176 41.612 2-'.564 60A42 36,745 7584 yean ............................................. 109,860 50A70 5-,850 101.088 45,932 ZS yrnrs and ovo ................................... 91,368 31.109 6C,259 86,358 29.217 1968 AII a9ee ............. ..................... ..... 300216 151,815 148 401 268,124 135.333 25J4 yesn,,..,,.................................... 390 262 128 211 166 3544 r.an................... ..,,,...,,,.,,,,~...».. 3,212 2.350 962 2,162 1,734 45{rt vean ................. »...... ,.,,»............ 12,953 9.412 3,541 9.727 7,545 55tS4 yesn..,.,,.•,•,,..... ..•.-••,••••,••••••••-- 34.475 23,481 10994 27,743 19,732 65•74yeera,,,,,,,,,,,,,,,_,..... .................. .. 71,905 41,270 30:i35 62.076 36.135 7584 years ............................................. 708,576 50.145 58.131 101,229 46,689 85 yeas enA 68,548 24,801 43,'47 64,870 23.269 Sooree: Rosenbe.p and Kleryba 132). 0 98 32,810 17,003 15,807 66 170 115 55 403 80o 539 261 2,167 3,056 1965 1,091 7,933 5,836 3.529 2.307 23,297 9,134 4,867 4,767 55,156 8,772 4.078 4.694 57.141 5,010 1 A92 3,118 132,791 32092 16,482 15.610 45 179 96 83 428 1,050 616 434 2,182 3,226 1,867 1.359 8.011 6,732 3.749 2983 24,941 9,829 5.135 4,694 54,540 7,347 3,456 3.891 4/,601 3.678 1,532 2,146

a their • 70s and 80s, they are roughly 1.6 and 1.4. The actual number of deaths involved is very large; their distribution by age, sex, and race is sho vn in Table 2. Between 1968 and 1976, a striking decline occurred in the acute myocardial infarction mortality rate for men and women of all ages and races. These are shown as percent changes of rate in Table 3. The percent change has been larger at younger ages (Tables 2 and 3). The ;hanges. for chronic ischemic heart disease are similar but les; dramatic (Table 3). ATHEROSCLEROSIS Differences in heart atta,-=k mortality rates among men and women parallel pathology data concerning atherosclerotic plaques of the coronary arteries. The International Atherosclerosis Project systematically collected autopsy observations on persons from 14 geographic locations and 19 ethnic groups in different parts of the world, and found that women from 11 of the 11) groups, when compared to their male counterparts, had a s much as or even more aortic atherosclerosis. Men over age 39 had more raised plaques in their coronary arteries thari women (23). These findings indic-.te that the occurrence of coronary plaques was parallel to neart attack rates, ' but that the occurrence of aortic les-ons was not. Coronary plaque .: : severity had a male-to-fPmale ra tio of 1.61 among whites : ;< and of 1.14 among blacks. Studies Sweden (39) and of westcrn Euro of a white population in peans from five locations :;:- - (17) demonstrate similar firidings: a clear excess of coronary ." atherosclerosis among men and a similiar severity of aortic atherosclerosis among men •;ompared to women. ' Autopsy studies thus show a selective liability of the male coronary arterial bed for atherosclerosis, as compared to the female, especially amoog white men but also among men of other races. The pathological findings are congruent with the clinical data on heart attack mortality rates. Autopsy studies also show that, among men or women with manifest coronary heart disease, wonien patients have roughly the same prevalence of advanced atherosclerotic lesions - of the coronaries as men (40). Ihese data suggest that the amount of atherosclerosis necessar_, to precipitate a heart attack is the same, on the average; in both sexes. This generalization about the amount of coronary atherosclerosis appears to hold 100 x:. ~;: r: - ~ ::: :_~:: S:= ~ ................. :i::icccc::::::::i:':: - { - -- : - - f: ::::'.:-::::::::.::::'.:`:::::::.::::::.::'::::::::.::.:..:::;:.:::::...:: '•:- ':-:':::': :: '..:::::: ..... .:............... ~:::: : -:.: . ~~.: _ - .::j.: -- _ .. ................ ........................................... ............-..................... .................................................................................................... .. ....... ....................... ............................................ ........................................... ................. .......... ........ ...-........................,............; ............;.... . .............................. ................. .................. ............... ........ ::~.:::::::.:w::.:•::::::~ ~ .......................... ............. 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for heart attacks at younger and older ages, for recent and otd infarcts, and coronary occiusion, without infarct, and for stenosis, as well as for complicated and calcified lesions and raised plaques In the coronary arteries (40). tt -shouid be noted that the grading of atherosclerosis at autopsy is not a simple matter because there are -severai types of lesions and several ways of evaluating or measuring them. Moreover, the development of the different sorts of lesions is not necessarily parallel. Sternby provides a useful discussion of issues in the grading of atherosclerosis (39). Nevertheless, the major studies noted above provide strong evidence that women have less coronary atherosclerosis on the average than men of the same age in the same population. RISK FACTORS Factors present in tndividuais which correlate with future liability to disease are risk factors for that disease. In the case of heart attack, for example, it has been shown that age, male sex, cigarette smoking, hypertension, elevated blood cholesterol, and several other conditions are positively and independently associated with the probability of heart attack. The level of high-density iipoprotein cholesterol in the serum has a negative correlation with heart attack; that is, higher levels are protective. The various risk factors have been identified for both men and women and have been shown on muitivariate analysis to be independent. A combination of risk factors is synergistic, producing an associated risk greater than the simple sum of the individual risks. Although the data for women are much less extensive than for men, they indicate that cigarette smoking is a major risk factor for heart attack in women. THE EFFECT OF SMOKING TIMN 0048318 Atherosclerosis There is little autopsy information about the amount of atherosclerosis in women smokers. Sackett and his associates reported on aortic atherosclerosis among both men and women: of their 450 female subjects, 309 were nonsmokers. , 52 smoked less than a half pack per day, and 89 smoked more (33). Mean, age-adjusted aortic atherosclerosis was found to

increase in conjunction with the amount and duration of smoking. A study of the ii-tramyocardia/ arteries and arterioles of the heart in 13 wom~n and 21 men who were nonsmokers, and 16 women and 27 men who were smokers, indicated that proliferative lesions in intramyocardial arteries were more advanced relative to age in smokers than nonsmokers. It was also found that subendo;ardial arterioles were thickened in smokers. A separate an_dysis by sex was not performed, but the authors remarked tha: the lesions developed as rapidly and as extensively in wome-i as in men in both smoking and nonsmoking groups (27). Studies of the s--verity of atherosclerotic plaques in the arteries of women °-Pho smoked in comparison with those who did not smoke invotv-s too few subjects to be satisfactory. Investigating the retatioitship of these arteriit lesions and cigarette smoking in wo+nen is fundamental to understanding the occurrence of heart tttack and other ischemic diseases. Coronary Heart Disease Coronary heart disease (acute myocardial infarction and chronic ischemic heart disease) occurs with greater frequency in smoking than in nonswoking women. The prospective study of Hammond and Garfinkel, published in 1969, included data on approximately 446,000 women between the ages of 40 and 79 (9). The increase ir, mortality ratios in conjunction with increasing numbers of cigirettes smoked per day for various ages is shown below in Table 4 (43,44). Mortality ratios were, higher for younger ages and lower for older ages. The one-pack-a-day smoker's' risk of death from heart attack was. approximately twice that of the nonsmoker. The prospective data of Shapiro and colleagues are based on a poputation of 120,000 men and women (35). Using a sampling factor of about one-thirtieth, they examined 4,301 women at risk of a first myocardiai infarction between the years 1962 and 1964. The smokers compared with nonsmokers had roughly twice as many rapidly fatal heart attacks and heart attacks that were not fatal within 48 hours. The ratio was approximately 2.9 among younger women ag-:d 45 to 54 and 1.8 for the subjects aged 55 to 64. Heavy smokers had higher ratios, but the data did not permit a detailed study of dose relationships or of the experience of fernate ex-smokers. - _ .:.:L._~:: ...;.~.... _ _ .... -- :.; . tY:::: ~~: - - ~...... : ::- . . ..Y - ' ........... - - :'... ~~. :::: . ..... . ........... --.. - _ ~ - - -

A recent study examines the cause-specific mortaiity of 6,194 British women physicians over the period 1951 to 1973 (6A). Table 5 pre-;ents the results of this study in conjunction with the_ previ•_,usiy published results among male physicians during the same period (6B). The clear association of cigarette smoking and ischemic heart disease previously described in males.was cootfirmed in female physicians. For women who reported smoki_ig 15 or more cigarettes per day, mortality due to ischemic ;ieart disease was more than double that of nonsmokers. . Although the results demonstrated a similar effect of smoking in the development of ischemic heart disease in both male and female physician=, the association of smoking with heart disease was less striking in women physicians. Ischemic heart disease was less prominent as a proportional cause of death in this population of women than in male colleagues (16 percent vs. 32 percent of il deaths). lschemic heart disease mortality was, only • 26 pe rcent higher for al l ever-smoked women than for never-smo';ed women. However, for females who sr'noked heavily (>25 cigarettes per day), the relative risk of: death from ischemic #'_eart disease was 2.2, a. finding consistent with that demons-:rated in males, who had a relative risk of 1.6. . In such studies, standardization for amount smoked daily by each. of the sexes does not, however, correct for differences in age at initiation of smoking and degree of inhalation.. This fact grea :ly complicates comparison of the magnitude• of biologic effect in the two sexes. This Ncohort effect" (i.e:, unmeasured but documented dissimilarities in total smoking experience) may lead to an erroneous interpretation that cigarez',e smoking Is less damaging to women .than to men. This issue cannot be resolved until studies. examine the effect of smoking in more recent cohorts of women whose lifetime s,aroking behavior is more similar to that of men. . Among 26,467 Swedish women observed during a 10- year period, , the risk ' of developing • fatal coronary heart disease was significantly higher among smokers than nonsmokers (49). The relative risk was 1.9 at ages 40 to 49 and 1.3 at ages 50 to 59. An extensive mortality study in Japan also reported a highly significant increase in deaths frdm ischemic heart disea:s among female smokers, with a mortality ratio for smokers of 1.6 (28). Coronary heart disea':-,e morbidity data are available on women from• prospective stul-ies in• Framingham, Massachusetts,

Tecumseh, Michigan, and the greater New York areas. The Tecumseh data of 1967 do not show a relationship of such morbidity with smoking (iabie 6) (7). The Framingham Heart Study found an increase-i risk for women smokers, but the associations were weak (18, 19). ' The study of Sha;iiro and colleagues considered both mortality and morbidity (35•). It reported separately on deaths -within 48 hours of onset, and on all definite myocardiai infarctions after that tim-: interv8i. Using this ctassificatioh, the incidence of coronary heart disease among women smokers was distinctiy higher than it was among nonsmokers. While there is some variability in the strength of this association, the data frovi the various prospective studies of mortality and morbidity Vom coronary heart disease establish smoking as -a positive correlate, or risk factor, for women. However, the risk ratios ;end to be smaller than for men at a given level of cigarette consumption In all age groups. This trend may result from the different smoking patterns reported by men and women who - noke the same number of cigarettes per day (6a, 6b,.24). Men generally begin smoking at an earlier age and have thui smoked for a longer time period than women. Men also in-iale more often than women and are more likely- to smoke rno,-e than half of a cigarette. These smoking styles would exNose men to a. larger dose of smoke per cigarette and a iLrger lifetime : amount , than that experienced by women. .. . Case control . and ~etrospective. studies of women who have had heart attacks have. suggested an increased incidence of heart attack among smokers. For example, a case control study of -55 - women who 1'ad heart attacks before age 50 (an uncommon event in women) found that . 89 percent were smokers in contrast to 55 percent in a control group without ! myocardial infarction. Heavy smokers' F: (35 or more cigarettes per day) had an estionated myocardial infaration rate approximately 20 times iiiat of the nonsmokers. As far as possible, women using orai contraceptives and those with other identifiable risk factors were excluded from the study (36). Spain and his as-ociates conducted a retrospective autopsy study of women Nho . had died suddenly of coronary heart disease and compa~•ed this verified diagnosis to the women's smoking habits is reported by the closest living relative (37). Only witnessed sudden deaths were inciuded in the data. Comparisons were made between women who had 'died of coronary heart dhease and women who died suddenly of causes other than he2rt attack. It was found that 62- ---- - ---------

percent of the women suffering sudden cardiac death were heavy smokers in contra-et with only 28 percent of the control group. For those who smoked heavily, the mean age at death was 19 years younger than that of nonsmokers; lighter smokers died at an intermediate mean age. In_ a_retrospective study emphasizing psychosocial variables, ._ . Taibott and associ_ates_ reported on 64 white women ,... who ..,die,..d__suddeniy of arterioscierotic heart disease (41).. Theyc... found • that womea who, died suddenly smoked more cigarettes than the com:iarison group. The relative risk for those smoking more than a pack a day compared with those smoking less than a pack a day was 3.9 (p <.004). Smoking, as well as other risk factors, raises the already somewhat higher risk of myocardial infarction among women who use oral con;raceptives. During the child-bearing years, the use of oral contraceptives doubles the risk of myocardial infarction; women who both smoke and use oral contriceptives have approximately 10 times the risk of women who neither smoke nor' rise oral contraceptives (13). These Issues are considered bel ow in a separate section. Cessation of Smoking and "Tar" and Nicotine Content of Cigarettes Existing data ` are inad_quate to determine the effect of sinoking cessation on *the incidence of coronary heart disease in women. Hammond tnd associates (have reported that mortality rates from co-•onary heart disease were lower in women who smoked low- 'tac" and •iow-nicotine cigarettes (as soid'- in the. 1960s) than in those who smoked medium level products, and still lower than for those who smoked high- "tar" and high-nicotine ~iroducts; even so, the mortality rate for those women smoking iow-"tar", low-nicotine products was significantly higher than that of nonsmokers (10). Evidence considered ' below suggests that stopping smoking is beneficial in the treatment of women suffering from peripherai vascular Jisease. Angina Pectoris The Framingham Heart Study reported that there was a positive. association be't:veen smoking and angina pectoris among men but not 'among women (19). In an extensive study 108

smoking for both men and women (2.). The relative risk for , men was 3.9 and for women, 3.7. The association appeared to relate to hemorrhage. from ruptured cerebral aneurysms rather than to other conditions that may give rise to subarachnoid hemorrhage. A synergism between smoking and the use of oral contraceptives and subarachnoid hemorrhage is noted below (30). The Japanese study cited in the discussion of ischemic heart disease has also reported on 366 deaths from cerebrovascular disease among women who smoked (28). The risk ratios for subarachnoid hemorrhage and cerebral hemorrhage were both significantly increased among women smokers (p <.001) as was the risk rate for the category, "other forms of cerebrovascular disease" (p <.05). Arteriosclerotic Peripheral Vascular Disease Clinicians have noted that airteriosclerotic peripheral vascular disease is more common In men than women. Sternby has reported from autopsy studies that men generally have somewhat more atherosclerosis of the femoral and pelvic arteries than women (39). Kannel has reviewed the relationship of smoking to the incidence of arteriosclerotic peripheral vascular disease (18). In the Framingham Heart Study the incidence of peripheral vascular disease was increased among smokers of both sexes; cigarette smoking was as strong art independent risk factor in women as in men. Heavy smokers had a threefold increased inc idence. Weiss studied 245 women with arteriosclerotic peripheral vascular disease (48). Ex-smokers who had not smoked for 5 years or more had nearly a normal risk ratio of 1.06; those who had not smoked for the last 1 to 5 years had a risk of 1.70; continuing smokers of less than a pack a day, 5.15; pack a day smokers, 11.53; and those smoking more than a pack a day, 15.56 (relative to nonsmokers, 1.00). The Increased risk was particularly associated with proximal (aortoiiiac) disease, and there was less association with distal (femoropopliteal) disease. Age-standardized relative risk ratios for those smoking a pack a day were 30.06 for proximal and combined proximal and distal disease and 6.32 for distal disease alone. A retrospective study of 21"7 patients who underwent arterial reconstructive procedures of various kinds for peripheral vascular disease has been reported by Myers and

colleagues (26). Diabetics were excluded from the report. There were 164 male a-id 53 female patients. The late patency rate of the vaswilar reconstruction was followed for 1 to 4 years. The au:hors reported that the number of cigarettes smoked befor : surgery did not influence the outcome, but cessation of smoking after surgery had a favorable impact. There were no significant differences in outcome between men and women. The patency rate'*4 years after aortofemoral surgery wal 90 percent in those who smoked five or fewer cigarettes per day after surgery and 75 percent in those who smoked a greater amount. Following femoropopliteal reconstruc:ion, the 2-year patency rates were 95 percent for those wha stopped smoking, 75 percent for those smoking as many ts 15 cigarettes per day, and 65 percent for those who •;ontinued to smoke more than 15 cigarettes per day. : -. Aortic Aneurysm Studies have not been reported for women with respect to atherosclerotic aortic an=mrysm and smoking. Deaths for women are about one-fiftY- those for men (9). Hypertension Smoking is not associater; with an increased prevalence of essential hypertension in men or women (38). However, smoking does combine with hypertension (and other risk factors) as a risk facto • for heart attack, synergistical ly compounding the risk. Two recent case co,strol studies of rapidly progressive, severe or malignant hypertension have found that there is an overrepresentation of smokers among patients with this uncommon phase of hypert=nsion (3, 12). In one study of 82 patients who developed malignant hypertension, 67 were smokers. Thirty-three of those were women. In the study, 77 percent of the female •)atients with malignant hypertension smoked, .and only about -44 percent of those with. essentiai hypertension and of the general female population smoked. The difference is highly significant. A similar and parallel study of 48 patients with: nalignant hypertension contained 33 men and *15 women; 25 men (76 percent) and 8 women (53 ) percent) were smokers c.)mpared with 44 percent and 30 ---- - --- - --------------------------------- ----------- ~r ~..... ~~~--` w x= "-~'=:::- -- - ~ ~ ' - - - - - ..................................................... --' - ~ ==;~............................. :~ = _ -- ~~ ' :~...._ ..................-........__...........'..................._....

percent, respectively, of a group of 44 men and 44 women.' with nonmalignant hypertension. The difference is significant for men but does not reach significance for women. Venous Thrombosis The section dealing with venous thrombosis of the 1979 Surgeon General's Report noted a case control study by Vessey and Doll of 84 women who had venous thromboembolism (44). There wasr no significant reiationship to smoking, although- there was a'trend (p=0.08) reasonably attributable to chance (45). Similarly, Lawson, Dav.idson, and Jick reported no assoeiation with smoking among 60 premenopausal women who used oral contraceptives and who had uncomplicated venous thromboembolism (21 ). The Issue is reopened, however, -by a recent paper derived from the Walnut Creek Contraceptive Drug Study. The authors analyzed 38 cases of venous thromboembolic events among the approximately 16,700 women followed in the study. These women were matched with 8,174 controls from the same cohort, providing each case with 61 to 559 comparison subjects. The relative risk•of cigarette smoking was 2.6 with a one-sided p value of less than 0.01. On multivariate analysis, the smoking effect was independent and remained significant. Of the 17 idiopathic cases of thromboembolic disease, 65 percent occurred in smokers, while 33 percent of the controls were smokers. The relative risk for smokers was 4.2. Both smoking and oral contraceptive use were independent risk factors for venous thromboembolic• disease in this cohort of women (31). The same section of The 1979 Surgeon General's Report noted a controversy about whether smokers who suffered myocardial infarction had a relative protective effect from leg vein thrombosis in the immediate post infarction period (44). The authors did not provide an analysis for each sex. A recent investigation of women undergoing gynecologic operations has studied the incidence of deep vein thrombo-sis of the leg in relation to smoking. In the prospective study of 231 women, their smoking habits during the month before the operation were determined. The occurrence of deep vein thrombosis (DVT) was assessed by the radioactive fibrinogen technique, with routine scans on the first, third, and sixth postoperative days. Of the 231 patients, 99 smoked and 132 did not smoke. Eight of the smokers (8.1 percent) and 29 of

the nonsmokers (22 perc:nt) developed DVT. Following an analysis of other factors, the authors concluded that smoking provided an apparent "pro tective" effect against postoperative DVT, based on the. fact that smokers constituted only 21 percent of the patients with DVT. They also noted that the women who developed DV i weighed more than those who did • not and that smokers who developed DVT were more overweight than nonsmokers with DVT (5). In a continuing pro ipective study of the, relationship of blood clotting and blood =hrombogenic properties to ischemic heart disease, Meade ani associates have reported on a number of blood coagulation variables and their relationship to smoking among 1,426 men and 638 women in England (25). Forty-three percent of th_ men and 36 percent of the women were smokers. Smoking. was not found to have an effect In women on factors V or VII, fibrinogen, fibrinolytic activity, antithrombin lll, platelet adhesiveness, or platelet count. Smoking decreased fibrinolytic activity in iaen and decreased factor V1-11 activity In both men and women. Oral contraceptive users were found to show an increase in fibrinolytic activity only ii the women were nonsmokers. High-Density Lipoprotein High-density Iipoprotein -'HDL) is a protein complex that transports cholesterol in tte blood. A higher level of HDL is correlated with a redu-:ed risk of heart attack. It has been observed that women who smoke have lower levels of HDL than expected (1,4,8). ORAL CONTRACEPTIVE USE, SMOKING, AND CARDIOVASCULAR DISEASE

estrogens raised the level of HDL significantly aboave the levei. In nonusers while progestin use lowered it. Combination drugs tended to change the HDL level according to their relative estrogen-progestin formulation. The average HDL con- centration was reduced by smoking. Among nonsmoking women the HOL concentration was 63.7 + 16.8 mg(di. This was reduced by 2.2 mg/dl for those smoking half a pack per day; and by 7.3 mg/dl for those smoking one or more packs per day. A reduction In the HOL level among women who smoked was also reported from Holland. This study found an independent negative association with the HDL level among oral contraceptive users (1). It has been reported from long-term studies that women usingg oral • contraception have a two to threefold statistically . significant increase in risk of venous thromboembolic disease when compared to those using other forms of contraception (46). . This study concluded that smoking did- not significantly increase -tha incidence of venous thromboembolism (45). By contrast, the Wainut Creek Study reported that smoking contributed to venous thromboembolism among both users and nonusers' of oral contraceptives (31). Conclusions about the effect of smoking on venous thromboembolic phenomena, therefore, must be regarded as uncertain at this time since there are few relevant studies and they provide somewhat contrary conclusions. In 1973, the Collaborative Group for the Study of Stroke In Young Women estimated that the relative risk of cerebral ischemia or thrombosis was approximately nine times greater for women who use oral contraceptives than for those who do not. A detailed analysis of smoking was not presented, but one of the study's striking findings was the high proportion of women with stroke who currently or at some time ' smoked cigarettes regularly (73.8 percent), compared with smoking rates of 43.4 percent among neighborhood controls aged 17 to 44. The study also found an increase in hemorrhagic strokes among white women. Almost half of the hemorrhagic strokes were attributable to bleeding from congenital aneurysms leading to subarachnoid hemorrhage (6). Recently an' association between smoking and aneurysmal subarachnoid hemorrhage in both men and women has been documented (2). The Walnut Creek Contraceptive Drug Study reported that in a cohort of approximately '16,700 women, the risk of subarachnoid hemorrhage for smokers was 5.7 times that of nonsmokers; the risk for oral contraceptive users was 6.5

times that of nonusers; and the relative risk for women who used both cigarettes and oral contraceptives was 22 times as great. Past users of oral contraceptives also had an increase in relative risk, but an analysis of risk was because of the small numb-ir of cases (30). not possible The risk of myocardial infarction in women is increased by cigarette sonoking and by the use of oral contraceptives; it is compo inded when both are used together. For example, Mann and associates reported a retrospective study of 63 women below ?ie age of 45 with acute myocardial infarction. The proportion of heart attack patients who had used oral contraceptives h- _ the previous months was signifi- cantly higher than expected. The relative risk for myocardial infarction among women srnoking 25 or more cigarettes per day was 11.3 times greater than- that among nonsmokers. Moreover, there was evidence for synergism of the two risks (22)• - . Jick, et al. reported a case control study of 107 women under age 46 who were discharged from the hospital after -- suffering nonfatal_, acute myocardial infarciions (14,15,16). The annual risk of nonfatal myocardial infarction (MI) among healthy women aged 39 to 45 who both smoked and used estrogens for noncontraceptive purposes was approximately 1 in 750. T'hey noted that although an acute myocardial infarction is tiocommon in healthy young women, the risk appears to be sub mantial in women over the age of 38 who both use estrogens and smoke cigarettes (16). In. this same study, i relative risk of 14 was reported for oral contraceptive us-:rs compared with nonusers (90 percent confidence limits =)f relative risk from 5.5 to 37) (15). In women smoking mD re than 25 cigarettes per day the relative risk rose to 34 ti, ies that of women who were both nonusers and nonsmokers. While the number of subjects was small, the authors calculate• I that for women exposed !o either oral contraceptives or smok 'ng, but not both, the annual age- specific risks for nonfatal' MI were roughly 1 per 190,000 at ages 27 to 37; 1 per 47,0C0 at ages 38 to 40; 1 per 23,000 at * ages 40 to 43; and 1 p-:r 16,000 at ages 44 and 45. If, however, both cigarettes an-1 oral contraceptives are used, the annual age-specific risk is estimated to be much higher and the respective irisks become I in 8,400; 1 in 920, 1• in 540, and 1 in 250. The authors report that a dose-response relationship exists between smoking and risk among their population of female myoca,dial, infarction patients, such that smoking 1 to 14 cigarettes per day carried a relative risk of 116 .................................................................................. •:w;:::::: :: •-.:~:: :::::..... ° :: ~~ - - - - - :. .............~............... _ _ .... _......_.M......... __ . - _ ,,,,_-_ - - :~X:- - . . ......_. . . ..._.._........ ................_. ... . ... .... .. .... .... - _ _._... w ...... .. _.......... _ _ .................................... ...... .......... ... ......_~,__ ,,.,... .._-.... . ...-_ :: :.._ . :::~ :: ~` atz:::»: ~ ........''r::: ~r ...._ .: ~t ..... ......_ .r.. .. yr . ...- .i,......_ Pe. .._~.........~c _:r-•.........~...........~.r.:: :::: .... ....._ ........ i:i~: - - _ = __-_ - :~ T I - M N 0 0 4 8 3 - 3 3

(18) KAMIEL, W.B. Epidemiologic studies on smoking G.f3. (Editors). Proceedings of the Third in: Wynder, E.L., -Hoffman, D., Gori, in cerebral andl peripheral vascular disease. Health Servite, Natlonal Institutes of _Health, Educ2tion, and We-Ifaro, Public Health Servi=e, National Institutes of Health, National Cancer Institute, DHEW Worid Conference on Smoking and Health, New York, June 2-s, 1975. Volume 1. Modifying the Risk for the Smoker. U.S. Department of Health, Education, and Welfare, Public Publication, (NiH) 76-1221, op. 257-274, 1976. (19) KAMiEL, W.B., C-STELLI, W.P., MCNAMARA, P.M. Cigarette smoking and risk of coronary heart disease. Epidemiotogic clues to pathogene- sis. The Fra,ningham Study. In: Wynder, E.L.,_Hoffman, D. (Editors). Toward a Less Harmful Cigare?te. National Cancer Institute Monograph No. -8. U.S. Department of Heaith , Education, and'Veifare, PublicHeaith Service, National Cancer institute, June 1968, pp. , . 9-20 (20) KURTZKE, j.F. Epidemiology of cerebrovascu- lar disease. In: Cerebrovascular survey report for the joint Council Subconmittee on (21) Cerebrovasculae Disease. The National Institute of Neurological and Conmunicative Disorders and Stroke and the National Heart and Lunt Institute. Revised.january 1976. U.S. De:partment of Health, Education, and Welfare National Institutes of Health, Public Health~-;ervice pp. 213-242. LAWSON, D.H., DAJIDSON, J.F., jICK H. Oral , contraceptive tse and venous thromboembolism: abscence of an effect of smoking. Rritish Medical journal 2: 729-730, September 17, 1977. (22) MAMI, J.1 ., VESS1-Y, M. P., TfinR(xGOC)D, M., DDLL, R. Myocardial infarction in young women with special reference to oral contraceptive practice. British Medical journal 2: 241-245 May 3, 1975. (23) MCGILL, H.C., JF. (Editor). The geographic pathologyofatheroscierosis. GeneralFindings of the Inte- rnational Atherosclerosis Project. Laboratory 1n•restigat.ion 18(5): 498-5A2, 1968.

(32) (33.). ROSENBERG, H.M., KLEBBA, A.J. in: Havlick, R.J., Feinleib, M. (Editor'sf. Proceedings Health, Public Health Service, Education,- and Welfare•, NiN Publication No. 79-1610, of'the Conferenc- on the necline in Coronary Heart Disease Movtality. U.S. Depar-tment of pp'. 11-39, 1979. SACKETT, D.L., Gi.6SON, R.W., RROSS, I.D.J., PICiCREN,. J.W.. Relation between aortic atherosclerosi's' and the use of cigarettes and.aicohol. An autopsy study. New England Jcvurnai of Medicine 279(26): 1413-1420, December 26, 196:;. . (34) SHAfIRO, S., SLONE, D., ROSENRERG, L., KAUFMAN, D.W., STOLLEY, P.D., MIETTINEN, O.S. Orai-contriceptive use in relation to myocardial infarstion. Lancet 1: 743-747, Ap r i 1 7,, 19.79. • (35) SHAPIRO, S., WE1NBLATT,. E., .FRANK, C.W., SAGER, R.V. l,rcidence of coronary heart disease in a population insured for medical care.(HIP). My)cardial Infarction, angina pectoris, and possible myocardiat infarction. American Journal of Puhiic- Health 59 (Supplement 6): '-101, June 1969. (36) SLONE, D., SHAPIRO, S., ROSENBERG, L., (37) KAUFMAN, D.W., HARTZ, S.C., ROSSI, A.C., STOLLEY, P.D., MIETTINEN, O.S. Reiation of cigarette smokin=; to.myocardiai infarction in young women. Ne•~, England Journal of Medicine 298 (23 ): 1273-12 r6,. J une 8, 1978. SPAIN, D.M., SIEGEL,, H., 13RADESS, V.A. Women smokers and sudden death. The relationship of cigarette sMoking to coronary disease. Journal of the "merican Medical Association 224(7): 1005-100r, May 14, 1973. (38) STAMLER, J., RHOMB.:RG, P., SCHOENBERGER, J.A., SHEKELLE, R.B., DYER, A., SHEKELLE, S., STAMLER, R. ,:'.',e WAMAKER, J. Mu i t i var i at e .anaiysis of t;ie relationship of seven variables to b1=)od pressure. Findings of the Chicago H--art Association Detection Project in Industry, 1967-1972. Journai of Chronic Diseases' 28(10): 527-548, November 1975. 124 ' ...................,.. .. ,. ........... ......._. ......... ....._.. .... ........... ..~" ..:: _:', - _ - _ %~. =„ . ~.., - -` :'.-:_ -- _.~.~ - .....:..-~ ~`:: ~..._.....;

WILHELMSEN, L.- Recent studies on smoking and CVn epidemiology: Scandinavia and some other Western European •,ountries. In: Steinfeld, J., Griffiths, W=, Rail, K., Taylor, R.M. (Editors). Proceedings of the Third Worid Conference on Smoking ind Health, New Yortc, June 2-5, 1975. Volume ii. Health Consequences, Edu•_,ation, Cessation Activities and Social Action. U.S. Department of Health, Education, and Welfare,,;_Public Health Service, National Institutes of Health, National Cancer Institute, HEW Pubtication No. (NIH) 77- 1413, 1977, pp. 1.'1-177. 126 '

studies, and studies of human tissues at surgery and autopsy have confirmed and extended those conclusions. Cigarette smoking is the majog cause of cancer of the lung in women. The risk increases °vith the number of years the individual smoked, the number of cigarettes smoked, the "tar" and nicotine level of the cigarette smoked and the degree of Inhalation, and is inversely related to the age at which the individual began smoking, being higher, for. those who begin •smoking at younger ages.' ' The- risk of developing cancer is diminished significan :ly by quitting smoking and is lessened somewhat by switc-iing to low-tar, low-nicotine filter-tip cigarettes (55, 59). Considerable evidence has. also shown that cigarette smoking is a significant cause--for women and men--of cancer of ;ie larynx, oral cavity, esophagus, urinary bladder, kidney, and pancreas. Much of this information has been -summarized n previous 'issues of the "Health Conseauences of Smckingp or the Surgeon General's Reports (45-55 ). Table 1 lists the new cases and deaths 'estimated to occur in 1980 for those cancers which are causally associated with cigarette smokiag (1). Smoking will contribute to 43 percent of the mai` and IS percent of the female newly diagnosed cancer cas=s in the United States In 1980 and to 51 percent of the male and. 26 percent of - the female cancer deaths. This table does not imply that cigarette smoking causes each of thes= individuai cancers. It does, however, identify the impact o F cigarette smoking on the major cancers now known to be ass.)ciated with cigarette smoking.- Most of the cases of cancer of the lung and larynx could have been prevented, as could a substantial proportion of. the cancer deaths at the other s ites listed. In this. 'chapt_sr, seiected. data on cancer and smoking among women will be reviewed and summarized. Where necessary for clari=,y, data previously reported will be summarized briefly. LUNG The lung is a complex organ lined by at least five types of epithelial cells, each of which theoretically might give rise to one or more types of neoplasm. In addition to the epitheiial cells, blood vessels aid connective tissue are prominent in the lungs. Both visceral and parietal portions of the lung are covered by synovial membranes, which also are subject to Ina ----- ~:; ~ ...._ ........... ~ ~-------- 2..

neoplastic transformation= The World Health Organization's c iassification of mal iRnasit tumors (25) (Tab te 2) inc ludes multiple histologie types_ of which epidermoid, small cell, adenocarcinoma, and larg= cell carcinoma are causally related to cigarette smoking ard display significant dose-response relationships' in epidemioloRie studies (55, 10). These four tumors are the most cowomon histologic types of lung cancer In both men and women. However, there are differences In the distribution of the different types of lung cancer in men and women and in smckers and nonsmokers. Epidermoid carcinoma. was the most common histologic type of lung cancer in the male smoker, whi e adenocarcinoma was most common in the female smoker ard in nonsmokers of both sexes In a series recently published from the Mayo Clinic (Table 3) (39). Other centers hav; similar data, although the propor- tions by histologic. type may vary with the pathologic criteria used,.. patient 'populatioi i, geographic location, and other factors. Earlier epidemiologic studies suggested that cigarette smokers were more likely to develop squamous-cell and small-cell lung carcinomi than other types. However, • more recent investigations indicate that all four major histologic types of lung cancer--im•iuding adenocarcinoma, which appears to be increasing rapidl-r in recent years--are related to cigarette smoking in both men and women (55). In 1980, of the estimated 117,0(x1 newly diagnosed cancers of the lung in the United States, 32,000 will be among women. There. will be an estimated 25,500 deaths from lung cancer in women (1). in 1950 women a-counted for approximately 1 in 12 of all lung cancer deaths. By 1968 the proportion was 1 in 6; in 1979 women dying of lung cancer will represent over one- quarter of all lung cancer victims. White women have death rates from lung cancer -:+hich are similar to those of nonwhite women, while the rates -)f white males remain below those of nonwhite males. These differences may be due to differences in the smoking habits of blacks and whites described elsewhere in this report_ Many prospective studies have found that the lung cancer death rate for sp+okers was far in excess of the rates for nonsmokers in both sexes; and as previously mentioned, the rates for male smckers dramatically exceeded the rates for female smokers. However, even the nonsmoking male had a higher incidence of, -nd death rate from, lung cancer than the nonsmoking female (11). This evidence suggested that 131 k.. : - E~:.- - - - '°r.- .....~.... .....::,~ ':• _..~~.a.-.. r :~ -_ ~,r ......~.. ~~ `- _ - .: _ -- c:: : ~: - ... . .... . ;:

TABLE 2. World Health Organization Classification of Malignant Pieuro-Puimonary Neiplasms I. Epidermoid Carcinw.--as If.' Small CeII'Anaplastic Carcinomas II1. Adenocarcinomas I. 'Brochogenic a. acinar b. papillary °,ith or without nocin IV. Lart'e Celi. Carcinocomas V. Combined Epidermol. and Adenocarcinomas V1. Carcinold Tuenors V11. Bronchial Gland Tu"iors 2. Mucoepidermold turmors /. Cylindromas' formation V111. Papillary Tumors o,' the Surface Epithelium IX. Mixed Tumors and C,rcinosarcomas X. Sarcomas X1. Unclassified X11. Melanoma XIII. Mesothellomas SOURCE: Kreybarg, L. (-!5). 132

TABLE 3.-Histolo;ic Types of P:iimonary Cancers in Smokers and Non Smokers Male Femaie Type Total ~~:•ikers Non- Smokers Smokers Non- Smokers Epidermoid 992 892 7 80 13 Small Ceil 640 533 4 In0 3 Adenocarcinoma 760 492 39 128 101 Large Celt 466 •389 16 . 46 IS Brdnchioio- aiveolar 68 35 4 13 16 TOTAL. 2,926 2,341 70 367 148 SOURCE: Resenow and Carr (-9). ~~.1IS -S

women might have a decreased susceptibility. to lung cancer. A more careful examination of the data indicates that most of the differences between male and female lung cancer rates can be explained by differ:nces in smoking habits and occu- pationai exposures. As •liscussed In other--sect4oa-s-.-of.-this report, - a smaller percentaae of women than men smoke and, when they do smoke, they are more likely to -adopt smoking behaviors that have been s~ own to have a lower risk of deve- loping lung cancer. That is, they smoke fewer cigarettes per day, inhale less, start smoking later In life, and are more likely to . smoke iow-t?r and low-nicotine and filter cigarettes. In addition, It is important to consider the cohort effects on the differences in rates between males and °females. Over 85 perce it of those who srteoke- regularly began between the ages of 12 and 25 (33). Men first began to smoke In large number-; just before and during the First World War: — As each sue_ eeding birth cohort passed through the age of Initiation (12 to 25), a•larger percentage began smoking until the groups born between 1915-1930 were reached (19a). In the bi,th cohorts born after 1930, fewer began to smoke regularly. The risk of developing lung cancer increases exponentially wit;i, age and duration of smoking, with the increase starting 15 t-i 20 years after the beginning of regular smoking. This accounts - for' the dramatic rise in the male lung cancer death ra :es noted in the 1930s. As those birth cohorts with* higher smoking rates replaced those with lower smoking rates, the _,ge-specific lung cancer rates rose steadily; and as each of the heavy-smoking birth cohorts grew older, their lung cancer ri-,k continued to accelerate,. resulting in a very steep rise in i,he overall male lung cancer death rate. The overall cancer rates among men will continue to 7ise (albeit more slowly) as those birth cohorts with the heaviest smoking prevai-=:nce replace those with lower prevalence in the older -Lge groups where the lung cancer death rates are the highest. As these birth cohorts with high smoking prevalence pass through the age groups and are replaced by birth cohort; with lower smoking prevalence, declines in lung cancer raies should be noted. They should be noted first in the age-specific death rates for the younger age groups and later in the overall lung cancer death rates. The i'irst indications of this change have been noted with a decline in the age-specific death rates in males born after 1930. 11: is therefore important to consider this cohort effect when examining the differences between lung cancer rates of men and women. 134

Women began to take up smoking in large numbers 25 to 30 years later than men (in the early 1940s). This rise in smoking prevalence was produced by predominently young women first using tobacco as cigarettes. This is in contrast to the rise in men which inc uded a substantial- percentage of men of all ages who switch-;d from other forms of tobacco use to cigarettes. The rise in lung cancer, rates in women occurred as those cohorts with high smoking prevalence reached the ages where lun_; cancer occurs with significant frequency (age 45 and over). Since most of these women began smoking cigarettes priOr to age 25 they would have at least 20, years of exposure by age 45 in contrast to the shorter durations of exposur: at age 45 for those men who switched to cigarettes from i--ther forms of tobacco around the time cigarettes first came i,ito widespread use. This greater duration of exposure at an;, given age for women in these first heavy smoking birth cohorts compared to the first cohorts in men, should resu 't in a more abrupt rise in lung cancer rates in women. Thi-; rapid rise in female lung cancer death rates began to be obs=rved in the late 1950s. As birth i~E.cohorts with higher smoking prevalence continued to replace those with lower smoking peevalence, the rates rose steeply, reproducing the phenomenon noted in maies 20 to 30 years earlier with some indication that the rise is even steeper for women. I f one subtracts =;5 years from the female cancer death rates in Figure 1, the 'rates for women are only slightly below the rates for men. rhis small difference is explained by lower prevalence of smoking and less hazardous smoking patterns of women and their less freauent exposure to occupational carcinogens. i'hus, close scrutiny of the trends reveals no substantial prote.-tive effect for women on the risk of developing lung cancer but rather leads to a sobering projection of a reprodution of the male lung cancer epidemic in women (Figure i). Geographic Differences Lung cancer death rates, ncluding all histologic types, are highest in industrialized c)untries where there has been a higher smoking prevalence for a longer time. Women in Scotland have one of the highest death rates from lung cancer of women of any country. Their tobacco consumption per smoker approaches that of. English and Welsh men (22). Current tobacco consumptiom by Scottish women is only a 135 •

little lower than the constimption of Scottish men 20 years ago. In England and Scotiand, where the -upper socioeconomic classes have reduced theie cigarette consumption in recent decades, there Is a significantly greater lung cancer mortality_ rate-.in the. lower socioeconomic classes among women (22). -Age-adjusted death rates for lung cancer in women in select countries indicate uiat women In Hong Kong have the• •high.est-rites, while those in,Scotland are second and those iif England and Wales are thirl. The United States ranked sixth world wide (1). Among nonsmokers, lung cancer Is found slightly more often In urban than In ruFal areas; however, among smokers the marked increase In Iimg cancer found in urban areas suggests• that urban living -.xerts a potentiating rather than an additive effect on the inci~ ence of lung cancer. Urban living has little~' independent efTect on , lung- cancer Induction in comparison with even . modest smoking of filtered low-tar and low-nicotine cigacettes• (L, 12). Smoking Pattorns_ Among_Women Although women tend 'to 'Gave different patterns of smoking than ~men, the relative.relationships between smoking and lung cancer are the same. Lung cancer rates for women who smoke increase with increased dosage as measured by several dosage measures, including number of cigarettes smoked per day,• duration , of smoking ;vabit,' degree of inhalation, age of Fnitiation• of. smoking, and the "tar" and nicotine level of the cigarettes• smoked. These data, obtained from several prospective investigations,: are examined in Tables 4, 5, 6, 7, g, • and 10. The more • cigarettes an Individual smokes, the more likely -that individual will die of lung cancer (Table 5). Overall, female cigarette smokers have 2.5 to 5.0 times. greater likelihood of dying from lung cancer than nonsmokers (Table 7).. As discussed earlier, when the full impact of the cohort • effect - is felt, this ratio will probably approach that for men (8 to 12). Doll, et al. • studied the cause-specific mortality experience among approxhiately 6,200 female physicians in England during the period 1951 to 1973 (9a). The results of this study are presented in detail in Table 8, which also includes data from a previous report on male physicians (9). It is apparent that, smoking and lung cancer are simi- tarly related in men and .romen. In both sexes, lung cancer 136 ~ ~ ~.~.... . ...... ....... .._..._.... .~._....._

TABLE 5.- A;e-adjusted relative risks of lung cancer by number of cigarettes smoked 4umber of Cigarettes Smoked Daily 20-39 40+ 8.6 2.4 14.7 4.9 18.8 7.5 1 -14 15-24 ' 25+ 7.8 12.7 25.1 1.3 6.4 29.7 SOURCE: Hammond, E.C. (14) and Doll, R. and Pete, R. (0, 9a).

TABLE 6.-Lung cancer mortal.ity ratios for females by duration of smoking: Swedish Study Duration of Smoking in Yeari INortality , Ratios Nonsmokers I.0 1-29 years 1..6 30+ years 9.6 SOURCE: Cederiof, R. (6). 139 •

Swedish Mta t 4 1.(f 8.?. Study Fema I e 1.0 . 4.5 SOURCE: Hammond, E.C. (14), Dolt, R. and Peto, R. (9, 9a), and Cederiof, et al. (6). ' 140'

TABLE 9.-AEe-ad(usted lung cancer nmsta/ity (T/N) ratios• for males and females, `,y tar and nicotine in cigarettes snaked Hale= Femalss Nt=Ir T/N 1.00 . Medium T/N to.r T/N 0.79 p.Ao •The mortality rati"e fot tfis c tegory with highest risk mad. 1.00 so that the relatiro re-luctions In risk with the of lower T/N citarettes corld be Pisualized. . SOINtC€t Hamnond, E.C. (14). was use 142 '

Mal es Femates 1.00 1.6 2.1 ;The mortality ratio for :he category with lowest risk was made 1.00 so the Increase in risk with smoking more cigarettes/day could be itiustrated. SOURCE: Hamnond, E.C. (1 ). 143 --

mortality was at least thr :e times as high in ever-smokers as In never-smokers, at lea-~t twice' as high in current heavy smokers (more than 25 c garettes) as in light smokers ( iess than 15 cigarettes), and eKhibited a significant dose-response relationship. The magnitlide of the smoking effect on lung --"- cancer , for females and males was approximately the same. The relative risks .r for mortality from lung cancer for moderate (15 to 24 cigarettes per day) and heavy (more than 25 cigarettes) smokers were 6.3 and 29.7 among females, and 10.6 and 22.4 for males. .. .. The authors empha;ize, however, that no conclusions can be drawn from this data about the magnitude of the biologic effects of srnokin=; in men compared to women. Since the authors documented di i'ferences in lifetime smoke exposure (later age at initiation ind lower prevalence of inhalation among females), lifetime ~_moking exposures between the sexes were not directly comparable. This issue will be resolved only when studies examine the effect of smoking in cohorts of wotnen whose lifetime smsking behavior more closely matches that of the men to whom they are compared. A' number of retrospective studies have examined the relationship of smoking and lung cancer in women. The 1971 HHealth Consequences of Smoking reviewed many • of'' these Investigations and showed a smoker-to-nonsmoker risk ratio ranging from 0.2 to 6.8 f•)r females. The reader is referred to this volume for a more detailed discussion of these studies. Results of these investigations reveal sex differentials similar to those found in the larger prospective studies, with males having higher overall lung cancer rates compared to females. However, the lung cancer rates of smokers are significantly higher than those of nonsmiokers for both sexes. Tiie, women . who smoke low-"tar", low-nicotine cigarettes have a'lower age-adjusted lung cancer mortality rate than women who smoke high-"tar", high-nicotine cigarettes. Women who s,aoke medium-"tar", medium-nicotine cigarettes have mortality rates In between (I5) (Table 9). However, even the low-"tir" and -nicotine cigarette smoker has a rate substantially higher than the nonsmoker. These data suggest so~ ie benefit from smoking Iow-"tar", row-nicotine cigarettes. However, a further comparison 'of women who smoked less than one pack of high-"tar", high- nicotine cigarettes daily with women who smoked more than one pack of low-"tar", low-nicotine cigarettes daily revealed that the smoker of more than a pack a day of tow-"tar", Cow-nIcotine cigarettes had over twice the age-adjusted lung 144

cancer mortality rate of the women who. smoked fewer cigarettes, but with high "tar" and nicotine (Table 10). In a retrospecti:s study standardized for duration of smoking, number of ci~arettes smoked, inhalation and butt length, long-term femal: smokers of filter cigarettes had a lower relative risk of 'd=,veloping cancer than smokers of non- fiiter cigarettes (59). Cessation of Smoking , Although the risk of developing lung cancer increases with age, both for smokers -ind nonsmokers alike, women in good health who quit smoking will, over a period of years, experience a reduction in their relative risk of developing lung ~ eveloping lu g cancer approximates cancer. About 1_ years after the have quit smoking, .the risk of d that of the nonsmoker. Experimental C2rcinogen-:sis Tobacco tars, tobacco smoke, and single or mixtures of chemicals found in toba-co smoke have been used with various species of animals in carcinogenesis experiments involving skin painting, subcutaneous injections, tracheobronchial implantation, and/or instillation and inhalation. Some experiments have reported sex differences in the occurrence of lung tumors following exposure to c1'romium oxide (30). However, in a recent monograph on lung cancer, separate reviews on tobacco carcinogenesis, radiation car- cinogenesis in the respiratory tract, and experimental models for studies of respiratcry tract carcinogenesis did not yield information suggesting that the mate lung of any of the species studied was moFe susceptible than the female lung to carcinogenic action by either tobacco products or radiation (16). The reader is referred to previous Smoking and Health Reports for summaries )f experimental tobacco carcinogenesis studies. LARYNX •THe larynx is a small, complex structure, which produces speech, controls the flow of air in and out of the lungs, and 145

prevents aspiration during r.wallowing. In 1980 there wilP be an estimated 1,700 new --;ses of laryngeal cancer and 60n deaths from that tumor in U.S. women (Table 1). Laryngeal cancer has occurred predominantly in men, but more and more women are developing lary~_geal cancer as their smoking and drinking habits come to ipproximate those of men. The maie-to-female ratio for laryngeal cancer exceeds that of lung cancer. Laryngeal canc,er occurs in the fifth, sixth, and seventh decades both in mesi and women. While the disease is ° uncommon, its incidence has continued to rise over the past quarter century, especially In women, substantially becausa of changes in their smoking habits. Cancer can occur e=ther in -the glottis (true cord, 70 percent of cases), or In t,e subglottie or supraglottic. region (false cord, 25 percent of cases). . Usually the neoplasm is epidermold carcinoma when examined histologically. Since a tumoe-" that - interferes w ith speech gives rise to early symptoms, glottic cancers are usualiy diagnosed at an early stage and are curable in over 60 percent of the cases. When the tumor arises in the subglottic or supraglottic region, interference with phonation or speech may. not occur as early as when neoplasm begins on the glottis. The tumor may, therefore, reach a greater size and be accompanied by significant local tissue in rasion and destruction as wel l as m.etastasis. Patients with tumors discovered when they are still localized in the laryn_: have approximately an RA percent cure rate, while advanced lesions have.a 33 percent 5-year survival rate. • Laryngeal cancer di_piays a strong dose-response rela- tionship with smoking,: increasing with the number of cigarettes smoked per day, the "tar" and nicotine content of the cigarettes smoked, the depth of Inhalation and number of years cigarettes were smo~.ed the risk of developing laryngeal cancer is inversely related to the age at which smoking began (55). A lower risk for laryngeal cancer has been demonstrated in women w;io used filtered cigarettes for 1 0 years or more compared to those who smoked non-filtered cigarettes. Nonetheless, the risk remained well In excess of that experienced by nonsmokers (58). Excessive use of alcohol by nonsmokers also results in an Increased incidence of iaryngeal cancer. Heavy drinkers of alcohol--that is, greater ;han seven ounces of whiskey or Its equivalent per day--who also smoke cigarettes have a greater risk of developing larynge= 1 cancer than If they either smoked or drank to excess alone. There Is a synergistic effect of .46 ..........__..~. .........._ . ...:..........._...: ---. ...........-.........._.... ' - _ -------------------------------------------- ......>....._..... ...:..... ...._.... ............... :Y .........:~.....-....~ _ =.. . ....... _ - -------- - .:.... : - -- aF5 --- x ~ ~ _ ... ._........._....~..;:.~:: .. .;."== - -- ~ ~„ ~ ~...... ..~..,. ~ ~ ~.~ ~.... 1:~... . . ....... ~ - -' ~~ ~~_- - t `~ -.. ... . . w~~ _ : .. ................... _ ~......._.....

Numerous retrospe :tive studies have shown a reia- tionship between smoking and urinary bladder carcinoma in both, men and women (19). The likelihood of either women or men developing -biadder e-mcer increases with the number, of cigarettes. smoked, the iuration of smoking, and tar .and nicotine content of the cigarette smoked. Changing to low- tar, low-nicotine cigarettes or more clearly, cessation of smoking, decreases the eelative risk of developing bladder cancer. The risk' of an ex-smoker developing urinary bladder cancer approaches that of the nonsmoker years after cessation (59). In prospective studles In Japan and Sweden, women who smoke are 1.6 to 2.7 =imes as likely to develop bladder 'a'ancer as non` smokers ( 7,5). In an international study of successive birth cohorts ~1 the United States, United Kingdom, and Denmark, Hoover and Cole found increasing rates of bladder cancer associated with increased cigarette smoking in men and women in both cuburban and rural areas and in all nationalities studied (19)w It has been estimated that 30 percent of urinary biaddev, cancer in women can be attributed to cigarette smoking (55), KIDNEY Cancer of the kidney will occur In 10,500 men -and tS,4M women in the United Stat--s during 1980 (1). Some 4,8t!0 men and 3,100 women will di-: of renal carcinoma (1). The 5- year survival rate Is bet:Ipeen 40 and 50 percent (1). While the overall classification of kidney carcinoma includes tumors of the renal pelvis and treter, the largest number of kidney carcinomas occur in the -enal parenchyma and are adenocar- cinomas. In retrospective stiidies, adenocarcinomas of the kidney are found more freouently in smokers compared with non- smokers in both men a-id women (55,57). In a large prospective study among U.S. veterans, the kidney cancer mortality ratio increas-:d from 1.0 (the baseline for nonsmokers) to 1.34 for those who smoked 10 to 19 cigarettes daily and to 2.75 for.men who smoke two packs or more each day (21a). No ia;rge scale prospective study of women and kidney cancer has bee reported to date. 150

2. Cigarette smoki~g accounts for 19 percent of all cancers newly diagnosed a_od 25 percent of all cancer deaths In women. In 1980, 32,000 of the es,timated 117,000 deaths, or over one-quarter of the deaths expected from lung cancer, wiii occur in women. 3. -Women_ cigarett-s smokers have been reported to - have between 2.5 and 5 th _ies greater likelihood of developing. lung cancer than nonsmoking women. 4. Among women the risk of developing lung cancer increase.s with increasing number of cigarettes smoked per day, duration of the smoking habit, depth of inhalation, tar and nicotine content of u e cigarette smoked. The risk is inversely related to the ag-: at which smoking began. S. A dose-response relationship has been demonstrated between cigarette smoking,-M cancer of the lung, larynx, oral cavityr• pancreas, and urinary bladder In women. 6.._ The rise In lung cancer death rates is much steeper in women tha t in men. It Is projected age adjusted lung cancer .death rate will surpass breast cancer in the early 1980s. * currently that the that • of 7. The rapid incre-Lse In lung cancer rates in women is similar to but steep-:r than the rise seen in men approximately 25 years earlier. This probably reflects the fact that women first begaa to smoke in large numbers 25-30 years after the increase in cigarette smoking among men. Thus, neither men nor wo.ien • are protected from developing lung cancer caused by ciga!-ette smoking. 8. Cigarette smokii--g has been causally reiated to all four of the major histolo:;ic types• of lung cancer in both women and men, inciuding, epidermold, small cell, large celi and adenocarcinoma. 9. The use of 'fiiler cigarettes and cigarettes with lower levels of tar and nicotine by women is correlated with a lower risk of cancer of the lung and larynx compared to the use of high tar and nic 3tine or unfiltered cigarettes. The risk posed by smoking low tar cigarettes, however, is clearly greater than that among feanaies who never smoked. 1 n. After cessation of cigarette smoking, a woman's risk of developing lung an•f laryngeal cancer has heen shown to drop slowly, equalling that of nonsmokers after 10-15 years. 11. Excessive ingest ion of alcohol acts synergistically with cigarette smoking to ncrease the Incidence of oral and laryngeal cancer In women. 152 -~";:: :: ~:: ;r:w __ - -- =-~ ~ - - . =~ ~ _ . - µ -- - - .=:... . .._ - . . ......................................... __ r.::._.._ ..........................._.............._...._.........._......

DOLL, R., PETO, R. Cigarette smoking and bronchial carcinoma dose and time relationships among regular and lifelong nonsmokers. Journal of Epidemiology and Community Health 32: 303-313, 1978. (11) FRAUMENI, J. Genetic Factors in. Cancer. Holland, J.F., Frei, . E. (Editors). Philadelphia, Pennsylvania, Lea and Febiger, 1973, pp. 7-15. (12) HAENSZEL, W., TAUBER, K.E. Lung-cancer mortality '(15a) HAMMOND, E.C., GARFINKEL, L., SEIDMAN, H., LEW, B.A. Some re~;ent findings concerning cigarette smoking in orig ins of human cancer. In: Hiatt, 1-1.H., Watson, J.D., Winsten, J:A. (Editors). Origins of Human Cancer. Book A: Incidence of Cancer in Human-;. New York, Cold Spring, Harbor as related to residence and smoking histories. li. . White feEnates. Journai of the National Cancer Institute -124: 803-838, April 1964. HALL, T.C. (Editor), Paraneoplastic Syndromes. New York, 'Acadey ay of Science, 1974, pp. 5-557. HAMMOND, E.C. Smoking in relation to the death rates of one million •nen and women. In: Haenszel, W. (Editor). .. Epidemiological Approaches to the Study of Canc-:r and Other Chronic Diseases. National Cancer Monograph No. 19. U.S. Depart- ment of Health, Education and Welfire, Public Health Service, National Cancer Institute, 1966, pp. 127-204. in relation to lung cancer. In: Lee, D.H.K. (Editor). Envieonmental Factors in Respiratory Disease. New York, Academic Press, 1972, pp. 177-198. _ ::..:: ::;:: ........... - - . .. - - ~~- - - -~~ : TIMN 0048371 ` ~: -- : ... ;° - ... Laboratory, 1977, pp. 101-112. HAMMOND, E.C. ' Smoking habits and air pollution HARRIS, C.C. (Edi tor). Pathogenesis and Therapy of Lung Cancer, New York, Dekker, 1978.. Cancer Congress, Florence, October 20-26, 1974. Amsterdam, Ezcep;a Medica, 1975, pp. 26-35. Factors. Volume 3. Proceedings XI International miology based o,i census population in Japan. In: Bucalossi, P., Veronesi, U., Casinelli, M. (Editors). Ca-icer Epidemiology, Environmental HIRAYAMA, T. Pra,spective studies on cancer epide- . 154

(34) NATIONAL CLEARIPIGHOUSE FOR SMOKING AND HEALTH. Teenage smcking. National Patterns of Cigarette Sm•iking, Ages 12 through 18, in 1972 and 1914. Department of Health, Public Health Service, Center for Disease Control, National CI-:aringhouse for Smoking and Health, 1974. (35) NATIONAL iNSTI i'UTES OF EDUCATION. Teenage smoking. National patterns of cigarette , smoking, ages 12 through 18, in .1979. Depart- ment of Health, Education and Welfare, National Institutes of Fiucation, April 1979. (36) NETTLESHEIM, P., HANNA, M.G., JR., DOHERTY, D.G., NEWELL, R.F., HELLMAN, . Effects of chronic exposure to Artificial smog and chormium oxide dust on the incidence of lung tumors in mice. Oak Ridge N2tional Laboratory Conference, 1978, pp. 305-320. (37) POLLACK, E.S., HORM, J.W. Trends ,. in cancer incidence and mortality, 1969-76. (Submitted for pubiicatioi) , (38) REDDY, C.R.R.M., SEKHAR, C., RAJU, M.V.S., REDDY, S.S., KAMESWARI, V.R. Relation of reverse smoking to carcinoma of the hard palate. Indian Journal of Cancer 8(4): 262-268, December 1970. (39) ROSENOW, E.C., CARR, D.T. Broncho.genic car- cinoma. CA L)(4): 233-245, 1979. (40) ROTHMAN, K., KE~1ER A. The effect of joint expo- sure to alcohol and tobacco on risk of cancer of the mouth and pharynx. Journal of Chronic Disease '25: i11-716, 1972. (41) SILVERBERG, E., HOLLEB, A.l. Cancer statistics, 1974. Worlwide epidemiology. CA 24: 2-21, 1974. (42) STELLMAN, S.D., AUSTIN, H., WYNDER, E.L. Cervix Cancer and --=igarette smoking: a case control study. American Journal of Epidemiology. (in press.) (43) STRAUSS, M.J. (Editor). Lung Cancer, Clinical Diagnosis and Treatment. New York, Grune and Stratton, 1977, - (44) TSO, T.C. Personal Communication, 1979. U.S. Department of Agriculture. 157 -- - - -- =>.~~ . . ...... . ........... - =:;;.:: .- .~:;,.~.M-r..::.,.... - . ::F.. ~. - E~ - F.~w - _ +~' - - - t:: .................. : ~_'. - - - f-• ~:~M;':r":~~;c::::::~;;::::F.::.:`?':;~ .:;~:°`.'," ~° .. ~'~

(45) U.S. PUBLIC HEALTH 'iERVICE. Smoking and Health. Report of the . Advisory Committee to the Surgeon General _f the Pubiic Health Service, Department of H-_,alth, Education and Welfare, Public Health Service Center for Disease _~ .. Control, DHEW Puttication No. 1103, 1964, 387 .__pp. (46) U.S. PUBLIC HEALTH SERVICE. The Health Consequences of Smoking. ' A Public Health Service Review: 1967. U.S. De"artment of Health, Education and Welfare, Public Health Service, Health Services and Mental Health Administration, DHEW Publication No. 1696, Revised, January 1968, 227 pp. (47) U.S. PUBLIC HEALTH S-;RVlCE. The Health Consequence of Smoking, 1968. Supplement to the 1967 Public Health Service Review. U.S. Department of Health, Education and Welfare, Public Health Service, Health Services and Mental Health Admnistration, Publication No. 1696, 1•968, 117 pp. (48) U.S. PUBLIC HEALTH S'=RVICE. The Health Consequences (49) (50) of Smoking, 1969. Supplement to the 1967 Public Health Service Review. U.S. Department of Health, Education and Welfare, Public Health Service, Health 'Services and Mental Health Administration, D;IEW Publication No. 1969-2, 1969, 98 pp. U.S. PUBLIC HEALTH S;RVICE. The Health Consequences of Smoking. U.S. Department of Health, Education and Welfare, ; Ptiblic Health Service, Health Services and t1ental Health Administration, DHEW Publication No. (HSM) 71-7513, 1971,= 458 pp. U.S. PUBLIC HEALTH S~:RVICE. The Health Consequences of Smoking. U.S. Department of Health, Education and Welfare, P-iblic Health Service, Health Services and Me, tal Health Administration, No. (HSM) 72-7516, 1972, .158. pp. (51) U.S. PUBLIC HEALTH S-=RV/CE. The Health Consequences of Smoking, 1973- U.S. Department of Health, Education and Weifare, Public Health Service, Health Service and Mental Health Administration, DHEW Publication No. (HSM) 73-8704, 1973, 249.pp. 158 --- - ------ ------- - --- ai:`.- :..Y ."".~':. .....~---.....~..::F~ ~ ..... ..... ;~. .~.. _ . ....~~,_: ~' _ .~:~ .:.~,.._ - - ~ ~; ....,w :.............~.~... -- ~' ~-=== = ' ........ .: . - ;';;:- ~ :......._... ....._....._ ..... :.......w:Y::....._....._....

TABLE 1: Age adjusted death rates irom COLD (ICOA 490-492 and 519.3) t960-1977 (per 100,000) . WHITE . Male Farl ale Male .1977 33.4 10.7 14.8 1976 33.5 10,1 14.9 1975 32.1 " 911 13.5 1974 31.1 RA - 13.7 1973 .31.4 7.8 14.1 1972 29.9 7.0 14.0 1971 28.6 6.5 13.2 1970 28.2 6.0 13.3 1969 27.3 °.4 12.8 1968 22.3 =.8 13.7 1967 19.9 =.1 11.5 1966 19.7 =-.0 11.0 1965 - 18.4 =!.7 10.4 1964 ' 16.1 . =;.4 9.2 1963 .' 15.9 9.5 1962 13.1 =!.0 7.7 1961 - 10.9 ~.7 7.0 1960 10.4 1.7 6.7 Female Source: Nationat Center for He.ith -tatistics. Vital Statistios United States 1960- t977 (50) " 162 •

white females and a twofold increase among nonwhite females. Mortality rates from these conditions for white and nonwhite males have also increased since 1967 (by factors of 1.9 and 1.5, respectively), but the rate of increase has not been as steep as that for women. Seven large prospective studies have shown a greatly increased mortality from COLD among smokers as compared to nonsmokers (8,15,20,21,35,36,45). These studies, presented in Table 2, represent over 13 million subject years of observation and approximately 270,000 deaths from all causes. The number of deaths related to COLD is probably underestimated since some of the deaths attributed to pneumonia or myocardial disease may have been due to complications of COLD. In addition+, these mortality figures do not include an appreciable number of individuals for whom COLD may have been a major contributory cause of death. For example, It is not uncommon for individuals to have COLD and lung cancer simultaneously. Two of these prospective studies have inciuded signi- ficant numbers of women. Hammond prospectively followed 1,003,229 subjects aged 35 to 84 (35). Nearly 93 percent of the survivors were observed for a 12-year period. Death rates from emphysema among women were much higher in cigarette 'smokers than nonsmokers. "Heavier" smokers (defined as either smokers of 20 or more cigarettes a day regardless of age when smoking was begun, or smokers of 10 or more cigarettes a day who had begun smoking before age 25) had a sevenfold increased mortality rate as compared to nonsmokers. Cederlof, et al. followed 55,000 Swedish subjects aged 10 to 69 for 10 years (15). The overall mortality rate from all causes among female smokers was 1.2 times higher than that of female nonsmokers. The death- rate from bronchitis, emphysema, and asthma among female smokers was 2.2 times that of female nonsmokers. However, the number of deaths due to COLD among women was small in both of these studies; consequently, the relationship with smoking Is more difficult to evaluate. Nevertheless, -a significant excess risk for reported mortality from COLD was present for female cigarette smokers as compared to female nonsmokers. Data collected by Doll, et al. examine the association of smoking and cause-specific mortality in 6,194 women physicians In England, observed prospectively over the period 1951 to 1973 (19). Table 3 presents the results of this study, including previously published results of a similar study amon-g male physicians over the same period (20). The

In summary, recent statistics indicate a rise in the reported death rate due to COLD among women. The two large prospective studies that included appreciable numbers of women found significantly higher mortality rates 'due to COLD among women smokers a_ compared to women nonsmokers. This relationship was iccentuated in heavier smokers. Mortality rates from COt.D among female smokers are considerably lower than ?.nong male smokers. This may be due to different smoking patterns and work exposure among men and women. SMOKING AND *THE 'EPIDE~.IIOLOGY AND PATHOLOGY OF COLD The prevalence of chronic bronchitis has been determined in several populations in the United States and in other countries (26,27,28,40,42,49,51,52,5•i,61). Tible 4 lists several studies which have included appr--iciable numbers of women. These studies have documented a close relationship• between cigarette smoking and' an increased ;.eevalence of chronic bronchitis, -and when looked for, a do=e-response relationship was also present (Table 3). The )revalence of chronic bronchitis in the United States was determined in four cohort studies and ranged from 4 to .10 percent among women and 14 to 18 percent among men (26,27,28,49,52,61). In both men and women a dose-response relationship between the number of cigarettes smoked and th-: prevalence of chronic bronchitis was apparent. The observed differ-:nces between men and women noted in these studies may be dle in part to the smaller percentage of women than men wPro were smokers in the population studied. Moreover these -•romen smoked fewer cigarettes than men. When comparing czirrent smokers, several studies of different populations in the United States and in England did not find significant differences in the prevalence of chronic bronchitis between men an-l women (23,38,49). The relationship between smoking and pathologic changes in the lung have largely been obtained by necropsy studies. These investigations are often skewed by physician and/or hospital interest and may not accurately -represent a random population. Moreover, observer variation occurs fre- quently, even among ee=perts " Data regarding smoking histo,ry are usually derived from a hospital record or from close relatives and friends; thus they may be unreliable. 166 ® ~- = .. .~......~. T ._:.^.~......~.<,-.......•. ~.~ .. ~.~...... ' ° ~ ' ._.... i~.

V ""'ART 1I® BIOMED3CAL ASPEECTS OF SMOKING . , TIMN 0048387

TABLE 5.-Means of average dayi:es of findings` in nonsmokers and current smokers standardized for age of total study population, women. -5ubjects Who Ptever Smoked Current Cigarette Smokers Regularly <1 Pk. 1+Pk. Number of Subjects 252 33 64 Emphysema 0.05 1.37 1.70 Fibrosis 0.37 2.89 3.46 Thickening of arterioles 0.06 1.26 1.57 Thickening of arteries 0.01 0.40 .0.64 •The pathologic findings reconded •-vere: (1) degree of emphysema (four-point scale ranging from zero for norma) to four :•)r advanced emphysema): (2) degree of fibrosis (seven-point snie ranging from none =-P advaneed diffuse fibrosis); (3) degree of thicken- ing of arterioles (four-point scale): (4) degree of thickening of arteries (three-point scale); and (5) padiike attachments to aiveo'- ^ septa. Padlike attachment is a thickening of alveolar septa in focal areas by fibro-'=sts. histocytes and coilagen fibrils. This is recorded as present or absent.. Souru: Auerbach, et al. (4) 170 - - - -------""" - - .:s:: ........... ................ ~ ^ •T~ ~- . . ~ = ..r.... ..« .«..w-«.._~.~~,~.ti..~+.K....,.,...;~r..- _ wY.C- .::L:.. ~- =:..--- - - ~M......_.... _. .._......~._......._.........__ .._........_.__ _ ~;.-' ...__._.......

21 • 6 . . . 22 • . 6 (0-20) 3 (10%) 66 11 (0-45) 5 (36%) . .62 - 14. (0--P0) .16 (39%) 52 2 (0-10) 0 6 (0-=0) 70+ s (0•_0). 5 (23%) 40 ••x2 tes-t shows significance at the 1~ level for the heavy smokers and nonsmokers. "Each whole lung paper mounted sc-tion'was graded from 0 to 100 in denominations of 5 up to grade 50 and then in denomi.tations of 10 up to grade 100. +One case. Source: Spain, et al. (60) 172

m m W.r ~ a a C w_ L ~ ~9 O V O VI o. 3 N N •! cc (D Cb L a > oOV°,+°' N m ZtnGON~ m ~ =1 ? a o - E t w L m Y Ey':. Ofn V! m O• m a7 ~ '::::::::::~::::: `i:::: '..: - :::~:° :. .................... , ::: _ ~''- .. .._ TIMN - ~.• : ............................•.....•..••.........•.............. r.:

TABLE 9.-Prevalence of respir_tory symptoms in men compared with women" COUGH' Men Women (Published Data) (Present Investigation) . Percent Percent Light smokers 24.' -(48) Moderate smokers 48-52 (48) Heavy smokers 42 . (46) 67-74 (47) 58-78 (48) SPUTUM Heavy smokers 42 (46) DYSPNEA All smokers 21 (49) Heavy smokers 33 (50) •Numbers in parentheses are refew snce numbers. Source: WouM(75) • 1 176 28 35 - --~. .:. - - ~-~~:. w~~ ~ :^~.r;..~-- • ...~_.__:.....::_ ~ : ~ ......i .. ::.: ::;= . ,. : =. . .w= - . . ......... ... ..........: --------------- -- ~C :.............M~~~~W - _ ~.

cigarettes smoked. Manfi=eda studied population samples in an urban and a rural commu!tity in Manitoba, Canada (47). Their data presented in Table 10 demonstrate a higher prevalence of cough, phlegm, and wheezing among men and - women . who smoked than in nonsmokers or ex-smokers. However, no significant differences in the prevalence of symptoms were apparent- in the two communities. •• -The relationship between* smoking and several - respiratory symptoms w is examined by Buist, et al. n in population samples of three North American cities (12). Cough, sputum production, and wheezing occurred more frequently among smokers than nonsmokers regardless of sex. Bewley and Biand examined the relationships between smoking and the prevalence of respiratory symptoms In 14,033 children aged 10 to 121J.; in two separate urban areas of the United Kingdom (9). In =his questionnaire survey, 2.5 percent of the girls acknowledged smokin at least one ci arette er g p g week ("smoker"). Boys who smoked outnumbered girls who-.,- .--.--w__m._. smoked by 3:1 and were more frequent smokers of at least one cigarette a day than- were females by 11:1. Table 11 shows that even in this young age group, smokers have a higher frequency of morn ng cough, cough during the day and ~ night, and cough for 3 m-mihs duration than their nonsmoking c lassmates. In a questionnaire study of a large group of American high school students *in :;ochester, New York, Rush found a strong association between current smoking and respiratory symptoms in both sexes (57). There were minor differences between sexes in the frequency of respiratory symptoms when smoking histories were comparable. Rawbone, et al. in a questionnaire survey of 1C,498 secondary school children aged 11 to 17 in London,- foun- a significantly higher frequency of ' cough, colds, and 'exertional dyspnea in regular smokers as compared to nonsmokers (55). There was no appreciable difference in the frequency of cough between male and female smokers or between mal-; and female nonsmokers. . Colley examined the influence of smoking, lower respiratory tract illness under 2 years of tge, social class of father, and air pollution on respiratory symptoms,in a cohort of 20-year-olds followed since birth (16). Their data (Table 12) suggest that respiratory symptoms were closely related to current smoking. Symptoms were also relat--rd to a history of lower respiratory trac; Infection in the fi -st 2 years of life but were not related to social class or air pollution. 178 - TIMN 0048396 :- -

TABLE 10-Respiratory sympto ns and diseases in male (M) and fecriale (F) par- ticipants in Charles.rood (C)-urban-and in Portage La Prairie (P) -rural-expressed =, percent of respondents. Respiratory Symptom/Disease Cough on most days, at least 3 months/year M F Phlegm on most days, at least 3 months/year M F Wheezing apart from coids M F M - F Shortness of breath compared to per- sons of same sex and age M F Smoking Category Nonsm=';ers ExSmokers Smokers C P. C P C P 8.3 4.0 8.1 29 25.4 31.5 - 4.0 - 10.0 20.3 31.7 - 4.0 10.8 5.7 16.9 24.7 .-• 4.0 - 5.0 10.2• 25.4 4.2 8.0 10.8 14.3 26.8- 31.5 3.5 8.0 12.1 20.0 25.4 30.2 4.2 8.0 13.5 11.4 11.3 17.8 - 12.0 6.1 15.0 13.5 20.6 8.3 4.0 • 5.4 5.8 5.6 12.3 7.0 12.0 6.1 5.0 22.1 17.5 Source: Manfreda, et al. (47) , .179 - - ..:...~~.~~ .:: : :: ~. ... ..."T.: .1 ~ : : . ..... {' ' ~..^~i. ~ ::^~:. • .T _ •- . ^:.Z.......... . .... ..~:... W.:w'..._ ..~.:..`.'.-~_. •...:"::'~......... . . r . -.~............ :"~ °r.~, ...'~.: »~... =- . ~ :-:: :~"~ w-: ` . ~:: --- r _ ,~ ........v....... " F=- t: - - ~~~ ~r_., _ r ::----- .......... - .. --------- --- : : ~ -~~ ~~ M -- ~~ _- . ......... ` :" "::`` Mr w= ~= ~~: :~:.:~ 4 . .....................__ . _ ~; ._ ._. ... .. ...- TI1~N ~~~V - ~.: 3

C'mC ~~i 6~ ' C r i~ ~ p, "- a a '•`:~ ~o w>> ~E t s ~ .'G e, a N gi' I O O Y ww+ m 41 u C 0 « C -aY O O ZH N N O N J J Q ~5 e ^'cc cr.. v O O m~~ O G!O ci Y O ... T> •w L >>" ~ ~~ S QCm j 7 7 3 7 . 8/ .'=.Oy~ 07 .t. 070 j. > » > y > O O O ~ O O O ~ O U COO : O .. 00 . -4a } ~ N ~ N N N } .2-3.° }= ` e 0 m fJ m ~ E O

~': ---- - ~ _ _ ::i:: .~ t~: _ - - :.. ..r:..::...._.._ - - - T----- - - _ _ ....... .......... _~.::_.:.:._..._.. _.....

...~~..~ ~ w)l..N r.....~ r.~~.r~. RV%TLC CV%VCE CC%TLC SIR III FEV10%FVC FIGURE 2.-Prevalence of lung function abnormalities among smokers in an urban (Charleswood) and a rural (Portage La Prairie) community. SOURCE: Manfreda, et al. (47) 185

100% 4 4,~~ 45''. 37 74 173 77 10-20 20-40 Cigarettes/Day 19 3 >40 FIGURE 3.-Percentage of ,_tate and female cigarette smokers with an abnormal change in nitrogen cor:entration MNZ ) per liter according to their daily cigarette consumption. An asterisk indicates a significant difference be• tween groups using 20 to 40 cigavrttes per day as the reference group (P <0.05). The dagger indicates significant difference between males and females (P <0.05). SOURCE: 8u1s1, et at. (t31 1 £6

male populations and have found a close relationship between cigarette smoking and t,'-e presence of. abnormal pulmonary function (2,6,18,22). Furthermore, the decrement In performance measured by simple spirometry is dose-related to the numbers of cigarettes smoked (6, 18, 22). Relatively few studies have included appreciable numbers of females. Woolf examined aulmonary function in 500 women volunteers (75). Smokers demonstrated significantly lower values for FVC, Fi:1/, ;-EF 25-75 percent, and specific conductance than nonsmo!,.ers and ex-smokers who had not smoked for over a year; this 'suggests that at least some .abnormalities of pulmon:.ry function are reversible with smoking cessation. . Higgins examined ;he relationship of smoking to seven derivatives of the forced vital capacity curve In 3,109 males and .3,256 .females aged 10 and older (41). Nonsmokers performed better than ;mokers in both sexes.. Values consistently decreased wi=h increasing cigarette consumption. The largest differences were In - FEV and FEF 25-75 percent. .Seltzer examined .t,`.: relationship of smoking to FVC in 65,086 white, black, and Asian subjects aged 20 to 79 who had attended a Kaiser-P=rmanente muitiphasic health clinic (59). The authors fou id. a significant reduction in FVC among white women who ;moked as compared to nonsmoking white women. No such differences were found for black and Asian subjects, however. No explanation .for this racial difference was apparent fr)m their data. In a study by Buist, the prevalence of abnormalities of FEVt/FVC was higher in female smokers than nonsmokers (12). The frequency of abnormalities in FEV1/FVC among female smokers was twice that of male smokers (Table 12). Gibson, et at. examined the relationship of smoking to measurements of the forcei vital capacity in 18,359 men and women in Australia (34). Nonsmokers had better lung func-, tions than smokers. Amon~- smokers of 10 or more cigarettes a day, men showed a greater decrement in lung function than women. Burrows examined the relationship of smoking to measurements of forced -a--cpiratory volume in 883 men and 1,166 women in Tucson, Arizona (14). Nonsmokers performed better than ex-smokers or imokers, and ex-smokers performed better than smokers in botti sexes. Smokers of more than 20 cigarettes per day perfon-ved worse than smokers of fewer than 20 cigarettes per day.. There were no significant dif- ferences in the regression 'or FEV1 /FZ/C on pack years in men 188 -

(34) 3.0 x '-"'X (38) 7e FVC e x o`-x L e x (39) _ -`~ f8) K ~ M (5 x x .0 A (a) e® (7a) x® (22) x X f®e .. X NON SMOKER 1.0 A HEAVY SMOKE: I I I 1 ____ !~ ~ 30 40 0 60 70 80 PG,E • YEARS FIGURE 4.-Changes in 1wled vital capacity (FVC) by age in various female cohorts. Results have ~,s standardized to 155 cm. and are body'tem- perature and pressure saturated (=3TPS). Numbers in parentheses rre number in that cohort. Heavy smokers are thc-se who smoke 25 or more cigarettes per day. SOURCE: Ferris (25) ' I ON .......... _:-~ ~c~~-` ~`eie::': _ "~~~"-~ ~~~~`~: ........ ~• . •::..: ..... E ..:: ~=::•; ••.,:;;, «.~ :~ ; ~-•-r~:~:: ;; s :~~: :aw '`~ : ~ ::::::: _ ::.. :•::::•~..~..:: -•- =2 _• : ~:=......-. ~-:~:.._.._......:;._...~ . .~ ~ • . ...... ...: =:~:=~..:...• ._....-:..~....._..~ ....._.......

Recent statistics indicat-s a rise in the reported death rate due to COLD among wom-en. The two large prospective studies that included appreciable numbers of women found significantly higher mortality rates d. e to• COLD among women smokers as compared to women nonsmokers. This relationship was accentuated in heavier = nokers. Mortality rates from COLD ' among female smokers aenidbl thl ,- coseray lessan among mae smokers. -This may be •!ue to different. smoking patterns and work, exposure among m` i and women. Women tend to smoke fewer cigarettes, inhale less deeply, and begin smoking later in life than. men. 'They more frequently smoke tow-"tar" and-nicotine cigarettes .,han men, and they work in cleaner environments than men. Recent data suggest that women are •manifesting smoking patt_rns similar to those of men and that more women are joining the labor force in occupations in which exposure, to tung. irritants may occur. Whether such women wilt-have mortality rates similar •to those of men remains to be determined. The prevalence of chronic bronchitis in women in the •United States has been estimated to range between 4 and 10 percent. This is lower :han the prevalence in men, probably reflecting the lower pe-centage of women who smoke, the fewer number of cigarettas smoked, and the reduced likelihood of occupational exposure to lung irritants. When comparing current smokers, several studies of different populations in the United States and England did not find significant differences in the. prevalence of chronic bronchitis between m.en and Women. Patriological data suggest that female smokers have a higher foequency of emphysema and bronchial mucous gland hypertsophy than female nonsmokers. Furthermore, the severity of emphysema is dose-related to the number of cigarettes smoked in women as well as in men. Distinct female-male difi'erences in the frequency and extent of emphysema at autopsy have been reported, but it is not clear whether these differences are due to intrinsic dif- ferences in the way men andn women respond to environmental Injury or to the differeaces in the degree of environmental injury experienced by meii and women. Many recent studies demonstrate a higher frequency of respiratory symptoms in -domen who smoke compared to women who do not smoke. This is true in surveys including children, adolescents, young adults, working age, and elderly women. The, effect of cigarette =noking Is dose-related for dosage 192 - _ :~ --: :° =<- =-=--~-- - ------------------------- ~ ~, .... -. k-................. ..._-. •. :::•••••••.»-••-•••••• ~..._._.».•.... ».............. .........».._..

NON-NEOPLASTIC BRONC: OPULMONARY DISEASES: REFERENCES (1) (2)' (3) (4) (5) (7) (8) AMERICAN COLLEGE OF CHEST PHYSICiANS. AMERICAN THORACIC SOCIETY. Pulmonary terms and symbols. :~ report of m Committee on -'uimonary _ 67: 583-593, 1975. ASHFORD, J.R., - BROWN, C.S., FAY, J. U.J. the ACCP-ATS Joint Nomenelature. Chest S., DUFFIELD, D.P., SMITH smoking • hab its and symptoms, ventilatory pneumoconiosis - imongst Scottish collie_•ies. Preventative and Social 1961. - ASHLEY, . F., K-~NNEL; MASSON, R. x~ulmonary The relation between physique, respiratory function, and radio- coal workers at three British Journal of Medicine 15: 106-117, W.B., SORLIE, P.D., function: Relation to aging, cigarette habit and mortality. The Framingham St•idy. Annals of Internal Medicine 82(5): r39-745, 1975. AUERBACH, 0., GARFINKEL, L., HAMMOND, E.C. Relation of Smoking and age to. findings in lung ' parenchyma: A- microscopie study. Chest 65 (1): 29-35, ' 1974. AUE.RBACH,~ 0., H_0.MMOND, E.C., GARFINKEL, L., BALCHUM, O.J., : FLETON, J.S., JAMISON, GAINES, R.S., CLARKE, D.R.; OWAN, D. England journal of Medicine 286(16): 857, 1972. BENANTE, C. Itelation of smoking and age to emphysema. `rhole-lung section study.. New 106, March 1961- 853- j.N., The Industrial ' Health Committee, The Tuberculo- sis • and Healtl-. Association of Los Angeles County. A survey of chronic respiratory disease in an Industrial city. Preliminary results. Am=rican Review of Respiratory Disease 86(5): 6F5-685, November 1962. BECKLAKE, M., PEkMUTT, S. The Lung in Transi- tion Between H-;alth and Disease: New York, Marcel Dekker, hic., 1979, pp. 345-387. BEST, E.W.R., JO`,IE, G.H., WALKER, C.B. A Canadian study of - mortality in relation to smoking habits ' A preliminary report. Canadian Journa of Public Health 52: 99- 194

(36) Smoking in relation to the death rates of one* million men and women. In: Haenszel, W. (Editor). . EpidemiloRicai Approaches to the Study of Cancer and other Chronic Disease;. National Cancer Institute Monograph 19. U.S. nepartment of Health, Education, and 'Weifare, U.S. Public Health, Service, . Natioaal Center Institute, January 1'966, pp. 127-204. Smoking and death rates months of follow-up on 187,783 men. 1. Total the American Medical HAMMOND, E.C., HORN, D. --Report on fo rty-four mortality. Journal of Association 166 (10): 1159-1172, MarcA 8, 1958. (37) HERNANDEZ, J.A., ANDERSON, A.E., JR., HOLPIES, (38) W,L., FORAKER, A.G. Pulmonary parenchymal defects in do_;s following prolonged cigarette smoke exposure. American Review of Respiratory Disease 93(1): .'8-83, January 1966. HIGGINS, I.T.T. Respiratory symptoms, bronchi- tis and disabifitv in a random sample of . an agricultural oopuiation. Rritish Medical J ournal 2: 1198 -1203, 1957. (39) HIGGINS, I.T.T., CDCHRAN, J.R. Respiratory symp- toms, bronchitis, and disability sample of =,n 'agricultural Dumfrieshire. 39: 296, 1958. toms, bronchitis and disability in a random sample of .n agricultural community in Dumfrieshire. 39: 296-301, 1958. HIGGINS, M.W., K1LER, J.B. Seven measures of ventilatory Aung function. American P_eview of Respiratory Disea m 10R: 258-272, 1973. in a random community in HIGGINS, I.T.T., COCHRAN, J.R. Respiratory symp- (42) HUBTI, E. Pre•-ralence of respiratory symptoms, chronic bronchitis and pulmonary emphysema in a Finnish rura' population. Field survey of age 40-64 in the Harjavolta area. Aeta (Supplement) 61:11,1965. . (43) HUTCHEON, M., GRIFFIN, P.,, LEVISON, H., ZAMEL, N. Volume oi` isoflow. A new test in detec- tion of miid' abnormalities of lung mechanics. American Review of Respiratory Disease 110(4): 458-465- October, 1974. : - ::r= ~~ ~-',- ~`~ ^'::`.:^ ~ : . , „~......._..........~:. w~ ~~.;~~...:._.. _ - _ - '- 198

::,, --- --------- ----- f ,........:.:..:,..._.._ ~ .............:::~ ~-----~--- x~~~ . . . - ---- - ------------ - -- - :i . . :':. ,:;;.... : •~ .~~~ ~Y...-..4~r.. r (44) IMBODEN, C.A., JR. Rising mortality from chro- nic respiratory disease. American Journal of Public Health 58: 221 -222, 1968. (Letter) KAHN, H.A. . The Dorn study of smoking and mor- tality among U.S. veterans. Report on 81/2 years of observation. In: Haenszel, W. (Editor). Epidemiological Approaches to the Study of Cancer and Other Chronic Diseases. National Cancer Institute Monograph 19. U.S. Department of Health, Education, and Welfare, Public Health Service, National Cancer I nstitute, J anuary 1966, pp. 1-125. (46) LEIBOWITZ, M., RURROWS, i?. . Ouantitative rela- tionships between cigarette smoking and chro- nic productive cough. International journal of Epidemiology 6: 107-113, 1977. (47) MANFREDA, J., NELSON, N., CHERNIACK, R.U. Prevalence of respiratory abnormalities in a rural and an urban community. American Review of Respiratory Disease: 117: 215-226, 1978. (48) MILLNE, J., WILLIAMSON, J. The relationship of (49) (50) respiratory function tests to respiratory symptoms and smoking in older people. Respiration 29: 206-213, 1972. MUELLER, R.E., KEBLE, D., PLUMMER, J., WALKER, S.H. The prevalence of chronic bronchitis,, chronic airway obstruction, and respiratory symptoms in Colorado City. American Review of Respiratory Disease 103: 209-22R, 1971. NATIONAL CENTER FOR HEALTH STATISTICS. Vital Statistics of the United States, 196A-1977. U.S. Department of Health, Education, and Welfare, Public Health Service, Office of Health Policy, Research and Statistics, National Center for Health Statistics. OSWALD, N.C., MEDVEL, V.C. Chronic •bronchitis: the effect of cigarette smoking. Lancet 2: 843-844, October 22, 1955. (52) PAYNE, M., KJELSF3ERG, M. Respiratory symptoms, lung function and smoking habits in an adult population. • American Journal of Public Health: 54: 261 -277, 1964. 199

(53) PETERS, J.M., FERRIS, B.G., JR. Smoking pulmo- nary function a_id respiratory symptoms in a college-age group_ American • Review of Respira- children in 1975 journal of Epidemiology and Community Health 12: 53-58, 1978. tory Diseases 95: 774,. 1967. PHILLI PS, A.R9., P: tlLLi P5, R.W., THOMPSON, J.L. Analysis •of etiologic factors in survey- of 1274 men._- . Annals • o F Internal Medicine 45: 216, 1956.: t : . RA1NR•ONE, R.,. .KEEL ' NG, C., J ENKI NS, A:, * GU Z, A. Cigarette •• smokiog •. among• y secondary school •(56) • REMINGTON, J. "hronlc . bronchitis, smoking and social class. A study among working people in the towns . of F-Lst and Mid Cheshire. F3ritish (57) to; smoking In a teenage., population: The re- sults of tow lhrked surveys separated by one year. International -• Journal of Epidemiology . 5 (2 ): . 173-1.78, 1976 Journal o.f, 'Disea-~e of the Chest 63 (4): 193- 205, 1969. .. • RUSH,• D. '• Changes in respiratory symptoms related (5R) RYDER, R:, DUNNiLL,..M., ANDERSON, J. - A quan- titative study of • bronchial mucous gland volume, emphysema and smoking in a necropsy popu lation. (59) SELTZER, C.C.,. S1EGELAUB, A.B., FRIEDMAN,. G.D., •COLLEN, M.F. Differences in pulmonary func- tion related to smoking habits and race. American Review of Respiratory Disease 110(5): 598-608, November 1974.. (FO) SPAIN, P., SIEGEL, ' H., RRADES, V. Emphysema in (61) (62) (63) apparently health_y adults. Journal of the American Medical . Association 224: .322-325, 1973, TAGER, I., SPElZEr_;, F. Risk estimates chronic bronchitis in . smokers: . A study male-female diffcrences. American Review Respiratory Disease s: 113: 619-625, 1976. THURLRECK, W.M. Aspects • of chronic obstruction. Chest 72: 341 -349, 1977. ~ logy. Philadeiphia, London, Sanders Co., 1976, 235-287. in lung disease. ". Major problems in patho- for of of airflow THURLRECK, W.M. Chronic Airflow Obstruction Toronto, W.R. 200 •

INTERACTI®N BETWEEN SMOKING AND OCCUPATIONAL, EXPOSURES I The 1979 Surgeon General's Report on the health consequences of smoking (18) examines the interaction of smoking and occupational exposure. Ways In which smoking may interact with the occupational environment are described and examples of these interaetions are discussed. Briefly, these types of interaction are: 1. Tobacco products may serve as vectors by becoming contaminated with 'toxic agents found in the workplace, thus facilitating entry of the agent by inhalation, Ingestion, and/or' skin absorption of the agent. 2. Workplace chemicals may be triansformed into harmful agents by smokinge more 3. Certain toxic agents in tobacco products and/or smoke may also - inhabit the ' workplace, thus increasing' exposure to the agent. 4. Smoking may contribute to an :effect aomparable to that which can result from exposure. to toxic agents found in the workplace, thus causing an additive biological effect. . ' S. Smoking may act synergistically with toxic agents found in 'the workplace to cause' 'a"much more profound effect than that anticipated simply from the separate influences of the agent and smoking added ,together. 6. Smoking may contribute to accidents in the workplace. Although few of , the studies discussed ' in the 1979 Surgeon General's Report included enough women to adequately determine the health risks for women of smoking and the occupational environment, It is reasonable to hypothesize that women with the same occupational exposure and smoking behavior as men would develop health effects similar to those demonstrated in men. However, the Interaction of smoking and the occupational environment and its effect on women differs in at least two ways:

First, smoking p?tterns among women are different from those among men--women are less likely to smoke, and if they do, they smoke tewer cigarettes per day, inhale less, and are more likely tw smoke lower "tar" and nicotine cigarettes (7, 17, 18). Second, smoking and occupational exposure may adversely ?ffect the fetus or the health of the mother during pregnancy. Smoking and occupational exposure may also interact with methods of contraception chosen by women. This- chapter reviews each of these reasons for a differential health impact on men and women and examines two occupational exposures where interactions with smoking have been clearly demons :rated for women workers. SMOKING PATTERNS IN 'VOMEN The male-female differ-_,nces , in smoking behavior and the • change in patterns of sanoking behavior in women over time are reviewed in other sections of this report. It is important, however, to •_~onsider the impact of these trends when evaluating the . interaction of smoking and the environment. Regular c`garette smoking is a behavior that usually begins between the ages 12 and 25 (18). It is unusual to begin regular cmoking after the age of 25 (7). In a cohort of individuals born In the same year, a certain percentage of them wil ; begin smoking by age 25. The prevalence of smoking i-1 any birth cohort after age 25 is predominantly determined by the rate at which people stop smoking or die. The pr avalence changes over time for each 10 year birth aohort since 1910 for both men and women are presented In the section of this report on patterns of t smoking. . Women first began smoking cigarettes in large numbers. immediately before and during the Second World War (18). Thus, the observed upswiag in smoking among women occurred 25 to 30 years after tha: among men. The birth cohorts with the highest peak smoking prevalence were born from 1910 to 1930 (men) and from 1920 to 1950 (women). As these cohorts with high preva ence of smoking grow older, they replace cohorts with lower srftflking prevalence. Since both occupational diseases and smoking related illnesses separately increase with age, any interaction between the two also could be ~expected to increase , with age. Men in the birth cohort from 191•0 to 1930 are now in the age range at which a high 204 •

TABLE 2.-Estimates of the Fercentags of Current, Regular Cigarette Smok.rs, Adults ages 20 Years and Over, According to Labor Force Status and Occupation and Sex, U.S., 1976 Total Currently empioyed White collar total trofessional technical and kindred Managers & administrators except farm Sales workers Clerical & kindred workers Blue collar total Craftsman & kindred workers Op.ratives and kindred .rorkers Laborer, except farm FemaIe s-)+ 20-44 45-64 = t.0 36.9 34.8 31.9 37.0 36.1 °_1.3 33.8 36.9 /.1 28.6 32.7 41.6 42.7 40.8 0 3=t.1 37.0 42.6 31.8 34.7 36.0 3•I.0 43.7 33.6 4-1.3 46.9 35.6 3r.6 42.3 31.2 5-i.3 52.6 • 3-/.0 42.8 37.2 31.2 51.0 0 4-1.0 41.0 39.2 2-).0 - 37.1 32.2 20+ 20-44 41.9 47.6 43.4 46.8 36.6 38.6 30.0 31.1 41.0 46.4 39.9 42.6 40.4 40.1 50.4 34.1 48.0 52.1 52.3 53.3 33.7 56.9 47.2 51.1 36.9 45.4 56.8 59.9 NA 45-64 41.3- 39.7 35.3 29.9 36.1 38.0 44.2 44.3 41.5 46.2. 31.7 44.$ • 35.0 53.8

PATTERNS OF EMPLOYMENT The percentage of women in the United States work force is steadily growing. In 1971 women represented 38.4 percent of the United States work fo rce and in 1978 that percentage had risen to 41.2 percent (15). Approximately .'39 million women are employed outsidea _ the home. Table 3 clearly indicates that the distribution of women in-the labor for :e by category of work does not parallel that of men. Women are more likely than men to be employed, in the clerical and service categories. Men are more likely to be empio•red in the management, crafts and operatives/transport categ: ries than women. Table 4 lists the number of women employed in a wide variety of occupations, including many of those tFaditionally believed to be hazardous for men. In spite -of th is diversity, the bulk of women ire employed - in a narrow rtnge of jobs. Over one-third of women in the paid labor iorce are employed in one of the 10 job categories listed in Table 5. All of these categories have been traditional employm-:nt areas for women. Thus, the recent gains by women in employment opportunity have not 'yet had a substantial impact cn the actual distribution patterns of the female labor force. If a shift does occur in employment patterns involving greater )roportions of women in occupations with significant exposures_, we would expect a cohort-effect to be apparent in the d:veloprnent of occupational illness. That is, those women entering hazardous occupations, tradi- tionally limited to male workers would be expected to be women newly entering the work force and, thus, predominantly in the younger age grolips. As these cohorts age, the duration of both occupat:)nal and smoking exposures would increase. It is only after these newer cohorts reach the ages, where disease is prevalent that we would be able to observe the full impact of occupa-:ional exposures (or their interac- tions with smoking) on the health of women. Because of this cohort effect, any failure to demonstrate an excess ris-, of a given occupational exposure in women must be interpr-:ted with considerable caution. It may mean only that the •.vomen exposed were too young and the exposure too brief for illness to have yet developed. This caution is doubly important for those attempting to demonstrate an interaction between occupational exposure and smoking on the developmen; of disease in women. Thus, little comfo,rt can be taken frcm the current low prevalence of occupational disease in women. It is reasonable 'to expect 208

..,:. :~.. ., ...;:.. . ~ - - - ..w . =:~ -~~ ~..•~'~......'l..~^~...... .. . ~. . ... . .......~"~:... =....=•Y: - ------------- :~w:. ~:iY . -- ----- - ---- - ---------- - -- - ---------------------- - TABLE 3.-0ecupational Distribution of Men and Women, 1978 by Percent of Each Sex Employed in Each Category Women Men Professional, Technical 15.6 14.7 Sales 6.9 5.9 Clerical 34.6 6.2 Operatives & Transport 11.8 17.7 Service 20.7 8.7 AlI Other 2.5 11.7 Crafts 1.8 21.1 Managers 6.1 14.0 Total 100 I00 SOURCE: Rones and Leon (14)

TABLE 4.-Number of Women In the Current Workforce, Classified Occupatlon White-coilar workers Professional & Technical Blolo~icaL-scl:niJ.sts Ch.mists Nurses, dieticians, & therapists Health technologists and technicians Engineering and science technicians Painters and sculptors Photographers Managers and administrators, exeept farm Sales workers Sales clerks, retail trade Clerical workers Bookkeepers Cashier s Secretaries Typists Blue-coliat workers Craft and ki•ndred workers Printing craft workers Upholsterers Operatives, except transport Assemblers Bottling and canning operatives Checkers, examiners, and inspectors; manufacturing Clothing ironers and pressers Cutting operative, n.e.c. Dressmakers, except factory Drillers, earth Dry wall instatiers and tathers Filers, polishers, sanders and buffers. Furnace tenders, smelters, • and pourers, metal Garage workers, and =as station attendants by Occupation (1978) Occupation # of Women In Thousands 24,594 Blue-collar workers-contld. 6,D83 Operatives, except transport- 22 continued 17 Punch and stampint press 1,2SS operatives 47 Sawyer 14 353 Sewers and stitchers 772 Shoennkinf machine operatives 60 132 Furnace tenders and stokers, 33 except metal 1 13 Textile operatives 224 Spinners, twisters, and winders 100 2,? SS Wsiders and flame cutters 41 2,-` i6 Winding operatives, n.e.c. 37 1,0/2 All other operatives, except 13,416 transport 1,062 1, 6-i0 Transport equipment operatives 258 1,212 Nonfarm laborers 492 3,5-i1 1,0-19 Service workers 8,037 3,7 r0 Private households 1,135 6-/4 Chiid care workers 477 .I1 Cleaners and servants 514 4 Housekeepers 117 4,3 7 Service workers, except 6-16 households 6,901 Cleaning workers 119 -!S Lodging quarters cteaners Buildins Interior cleaners, 174 3-9 n.e.c. 462 janitors and sextons 222 1.01 Food service workers 2,951 4 Bartenders 111 113 Waiters'-assistants 4S 2 Cooks 678 Dishwashers 82 1 Food counter and fountain workers 397 Waiters 1,252 Food service workers. n.e.c. 384 © Health service workers 1,660 Dental assistants 128 =0 Health aides, excluding 210

TABLE 5.-Most Conmon Female Job t:ate=orles, by Percentage of the Female Work Force Employed Pircent of F=maie ob ' Wo_rk Forc= ob Percent of Femate Work Force _ Sacretary 8.5 Privats Household Worker 2.9 Rstaii Saiss Clerk 4.3 Re=istersd Nurse 2.8 Bookkeeper 4.3 Elementary School Teacher 2.8 Waitress 3.2 • Typist 2.6 Cleaning Workers 2.2 Cashier 3.1 ' Sswer & Stitcher 2.0 SOURCE: U.S. D.partment of LAbor (17) , 212 * TIMN 0048430 .................................... .................................... .................................... t::

~ ~ .......•. ......~..,.. _ -"'. -- ~..~........._,._.. --.-.~.--,~,.... ~~'=... . .. . ....:w - ........... ~ . ;:,~~ ~- -~ - - :...... - --~ _ • ~~~~ , ,~.~ •,- , . - W ~~- ' ... . . ::~M - -a:: r that any movement of large numbers of women into hazardous occupations will be followed, after an appropriate time lag, by a dramatic increase in the prevalence of occupational illness in women. THE REPRODUCTIVE ROLE A third reason for examining the effects of exposures in women separately from those in difference in their reproductive roles. . Toxic occupational men is the occupational exposures in both men and women can 'reduce fertility and increase frequency of teratogenic,effects (see Table 6). In addition, however, the 9-month duration of gestation provides many oppo,rtunities for the fetus to share any adverse toxic exposure of its mother. These risks -may interact with the well-established risks of cigarette smoking during pregnancy discussed elsewhere in this report. Table 6 provides a'list of hazardous substances in the work environment, some of which are suspected of having effects on reproduction. Another specific concern. for - women is that of contraception. The type of contraception bsed often depends upon decisions by the woman, and substantial numbers of women in the United States who use oral contracept,ives. (18). These drugs have been shown to interact with cigarette smoking to produce a greatly increased risk of cardiovascular disease, as discussed in this report. In addition, it is possible that oral contraceptives may interact in an adverse manner with physical or chemical agents found in the work place, or that the combination of smoking, occupational exposure, and oral contraceptive use may bear special risks. The answers to those questions can be found only through the study of populations of wo'rking women. One study approached this Issue by examining the health status of women involved in the manufacture of oral contraceptives. Poiler, et al. have shown that women working in the manufacture of oral contraceptives absorb enough of the drugs to influence the clotting mechanism as well as alter menstrual function (12). Unfortunately, the risk of cardiovasculir disease--and the effects of smoking in relation to it--could not be estimated in this population. Because of the established excess risk of cardiovascular, disease from concurrent smoking and oral contraceptive use, examination of cardiovasular risk In this group would be of interest. 213

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lung and pleura was foun i among those who were severely exposed and who had worced less than two years. In the group with severe exposur-i for more than two- years in the factory, excess deaths from cancer of the lung, pleura, and non-neoplastic respiratory .iisease were observed. The authors calculated the excess anmial mortality due to lung cancer. Women workers_ with low-*_•i-moderate exposure experienced a mean excess lung cancer wortality of 63 deaths (per 100,000 years' exposure). Those severely exposed for less than 2 years experienced an excess of 44 deaths, and those severely exposed for •. 2 years or IW iger experienced an excess of 241 deaths. Interestingly, an examination of deaths did not reveal any significant association -+vith age at first employment in the asbestos factory. In t,`_e sub-sample of workers whose smoking histories were av2ilabie, those women who had both smoked and- were • heavily exposed had a risk of developing lung •cancee over „30 timei that of non-exposed nonsmoking women. The authors• conc-uded that the data suggested that asbestos and cigarette smoking exert multiplicative rather than merely additive effects. In summary, the da*_i on smoking and asbestos exposure in women closely resemble the findings demonstrated• for men. Approximately 250,000 wowen were employed in the textile industry in. 1978; that population Included approximately 100,000 women engaged i-i spinning, twisting, and winding operations. Byssinosis- s a syndrome characterized by tightness of the chest an-i shortness of breath in workers exposed to dust of cotton , flax, and hemp. In addition to these acute symptoms, wo •kers have been found to develop chronic bronchitis, and som s become severely disabled by their obstructive lung disease (3). Berry, et al. studied the workers in 14 cotton and two man-made fiber mills in England (1 ). They found that men had a greater prevalence of byssinosis than women, Lnd that smokers of both sexes had 1.4 times greater prevalence of byssinosis than nonsmokers. Byssinosis prevalence was also • positively associated with length of exposure to cotton dust in both women and men and was positively associated with dust level In the working environment in women. Berry, et al. were unable to determine If the observed difference in prevalence by sex represented a difference in physiologic response or differences 218 ` TIMN 0048436 i*?: ~-- ~{:~ --

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r 1NTERACTION BETWEEN SMOKINGAND OCCUPATIONALEXPOSURES: REFERENCES (1) (2) (3) BERRY, G., MCLYNEUX, M,.K.B., TOMBLESON, J.B.L. Relationships between dust level and byssionsis and bronchitis in Lancashire cotton mills. British Journai of Industrial Medicine 31: 1•8- 27, 1974. BERRY, G., NEWHOUSE, M.L., TUROK, M.E. Combined effect of asbestos exposure and smoking on mortality from lung cancer in factory workers. The Lancet 2(7775): 476-479, • September 2, 1972. BOUHUYS, A., SCHOENBERG, .'J.B., BECK, G.J., SCHILLING, RS.F.- Epidemiology of chronic lung 'disease In a cotton mill community. Lung - 154: 167-186, 1977. (4) HAMMOND, E.C., SEL/KOFF, I.j. Relation of (5) (6) (7) cigarette smoking to risk of death or absestos-associated disease among insulation workers in the United States. ln:. Roguvski, P., Gilson, j.C., Timbrell, V., Wagner, J.C., Davis, W. (Editors). Biological Effects of Asbestos. International Agency for Research on Cancer, Scientific Publication No. 8, Lyon, Lyon, France, International Agency for Research on Cancer, 1973, pp. 312-317. KILBURN, K.H., KILBURN, G.G., MERCHANT, J.A. Byssinosis: matter from tint to lungs. American journal of Nursing 73(11): 1952-1956, November 1973. NATIONAL CENTER FOR HEALTH STATISTICS. Health Interview Survey, 1976. (Unpublished data.) NATIONAL CLEARINGHOUSE FOR SMOKING AND HEALTH. Adult Use of Tobacco, 1975. U.S. Department of Health, Education, and Welfare, Public Center for Disease Control, Bureau of Health, Education National Clearinghouse for Smoking and Health, June 1976.

(8) NATIONAL CLEARING`IOUSE ON SMOKING AND HEALTH. (9) Survey of Heait;i Professionals: Smoking and Health, 1975. U.S. Department of Health, Education, and Nelfare, Public Health Service, Center for Disease Control. Bureau of Health Education, National Clearinghouse for Smoking and Health, June 1-/76, 42 pp. NATIONAL INSTITUTE FOR OCCUPATIONAL SAFETY AND HEALTH. Occupational Diseases (Revised Edition). U.S. Department of Health, Education, and Welfare, Public H-saith Service, Center for Disease Control, Nationa Institute for Occupational Safety and Healt,`. Superintendent of Documents,. June 1977, 608 pp. (10) NEWHOUSE, M.L. Cancer among workers in the asbestos textile Industry. In: Buguvski, P., Gilson, T.C., TLgibrell, V., Wagner, J.C., Davis, W. (Editors). Biological Effects of Asbestos. International Age:,cy for Research on Cancer, Scientific Public2tion No. 8, Lyon,' France, International Age,cy for Research on Cancer, 1973, ppp. 203-208. •(11) NEWHOUSE, M.L., BFRRY,. G., WAGNER, J.C., TUROK, M.E. A study o° the mortality of female asbestos workers. British Journal of Industrial Med'acine 29: 134-141, 1972. (12) POLLER, L., THOMSON, J.M., OTRIDGE, B.W., YEE, K.F., LOGAN, S.N.M. Effects of manufacturing oral - contraceptive ; on blood clotting. British Medical journal 1: • 1761-1762, June 30, 1979. (13) PROCTOR, N.H., HUt-~HES, J.P. Chemical hazards of the workplace. Philadelphia, J.B. Lippincott Company, 1978, 53=1 pp. (14) RONES, P., LEON, ~-. Employment and unemployment during 1978: An analysis. Special Labor Force Report 218. U.S= Department of Labor . Bureau of Labor Statistics, 1979. (15) SELIKOFF, i.J., HAM&iOND, E.C., CHURG, J. Asbestos exposure, smoking, and neoplasia. Journal of the American Medical Association 204(2): 106-112, April 8, 1968. , 222

A woman who, smokes during pregnancy not only risks her own health, but also changes the -onditions under which her baby develops. Studies have identified specific areas in which the effects of maternal smoking during pregnancy may occur. These include fetal growti, most ofien determined by comparing birth weights of smokers' babies with those of otherwise similar nonsmokers' babies; fetal survival, including the occurrence of spontaneous abortions, fetal deaths, and neonatal deaths; pregnancy ?omplications, including those that predispose to preterm delivery; possible effects on lactation; and long term effects on sur•.,iving children. The relationships between maternal smoking and these outcomes have been established- by clinical, pathological, and especially epidemiological studies. Understanding of mechanisms by which- smoking may produce the observed effects has been gained by physiological sturiies In humans and experimental studies In animals. . The Chapter on Pregnancy and Infant Health In the 1979 Surgeon General's Report Is a detailed review of past studies of the effects of smoking in pregnancy, with a* comprehensive bibliography. . This section summarizes current knowledge in major areas of study, describes important new studies, and points out area= requiring further research (150). SMOKING, BIRTH WEIGHT, AND FETAL GROWTH Babies born to women who s ' moke during pregnancy are, on the average, 200 grams tighte r than bab ies born to comparab le women who do not smoke: iince 1957, when Simpson reported this finding from her origi.ial study (142), it has been con- firmed in more than 45 s=udies of more than half a million births (150). Results of ti-ese studies are expressed as mean birth weights of smoke.rs' and nonsmokers' babies or, alternatively, as the percen:age of babies who weigh less than a specified amount, usually 2,500 grams. To illustrate the as-ociation between maternal smoking and an increased proportio-t of low-birth-weight infants, the results of five studies with an aggregated total of almost 113,000 births in Wales, ~.he United States, and Canada are suinmarized In Table 1. 1a these populations, 34 to 54 per- eent / of the mothers , smo`ced during pregnancy and on the average had twice as ma,iy low-birth-weight babies as the 224 ::~~,;. ..::~~ ----------------- -- ~~r ....~. ~......:..r:X" =r; „ '~' "' r•:...r.....-. .. 'w~ir . ~ . . . _ -- ~ ~...-..' ~ .._ ~ . .. . "......:'w:: . ~. "~. . . . TIMN 0048442 i::

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nonsmokers (3, 16, 42, 90, 106, 110, 111). One study in which rates of low birth weight were simultaneously adjusted f-ir multiple factors showed that maternal smoking had am_re significant relationship to birth weight than did previous pregnancy history, hospital pay status, mother's prepregnan-, weight, height, age-parity, or sex of child. Adjusted rates ---f birth weights under 2,500 grams were 49 per thousand for nonsmokers, 76 per thousand for smokers of less than. a paak per day, and 114 per thousand- for smokers of a pack per day or more. The risk of having a low-birth-weight baby t;ierefore increased 53 percent and 130 percent for light Lnd heavy smokers, - respectively, compared with nonsmokers ;90). Population studies t:iat illustrate whole distributions of birth, weights by maternal smoking levels show a downward J shift of all birth weights n proportion to the amount smoke d (81, 87, 118, '78, 140, 16-i) (see Figure 1). ~ These.studies sho:r that - the ' relationship between ! smoking and reduced birth weight is independent, of al i other factors ` that influence bi,th- weight, such, as race, parity, maternal size, socioeconomic status, sex of child, and other factors that have been studied. It is also Independent of gestational age. There is a dose-response relationship; that Is, the more the woman swokes during pregnancy, the greater the reduction in birth wei ;ht. If a.women gives up smoking by her fourth month of ;estation her risk of delivering a low-birth-weight baby is similar to that of a nonsmoker. Placental Ratios Analyses: of placental weig;its by maternal smoking habits have noted that these weights were either not affected or were less affected by maternal smoking than were birth weights (62, 66, 95, 108, 159). The placental ratio, the ratio of placental weight to birth weight, tended to be larger for smokers than for nonsmokers, mainly because of the dose- related reduction in birth weights with increasing number of cigarettes smoked. Wingerd and colleagues have studied placental ratios based on data from 7,000 pregnancies among members of the Kaiser Foundation Health Plan in Oakland, California (161). Smoking information was obtained early in pregnancy, and placentas were handled ac•:ording to Benirschke's standardized protocol. Figure 2 show Etacental ratios by smoking level and 226 • - ----- - ------ - --- _. ~ _~ ..._.....~. _ - - -F~..~....._. ~ - _ ~ ~ -- - ~.w - - ~.`=: ~,;..... - ;: :=.: ; .. - : ~ ~:' 7. _ :fi° -~~ ~ :~:~: : : °:~:::= ._- ~ ~ _ :'= '~

FIGURE Z- Ratio• oi plecental weight to birth weight by- iength of gestatiomi and materal smoking category. 15.5 15A -{- 14.5 + 14.0 a- 13.5 a- 13.0 J.. 37 38 39 •- 40 ` , 41 42 43 Week of geatation SOURCE: W ingerd. J. (161) 228

gestation for single live births to black and white women., At each gestational age, from 37 through 43 weeks, the more the mother smoked during pregnancy, the higher was the placental ratio. These ratios were higher for black than for white women and tended to increase as maternal hemoglobin level decreased (161). Christianson has reported recently. •(1 979) on the standardized examinations of these placentas. The increase in placental ratio with maternal smoking level was due to considerable decreases in mean birth weight, accompanied by slight increases in mean placental weight. In addition, smokers' placentas were significantly thinner than those of nonsmokers, and their minimum diameters were larger (20). Maternal smoking leads to significant increases in car- boxyhemoglobin in maternal and fetal blood, with a consequent reduction..jn the oxygen carrying capacity of both, and a reduction of the pressure at which oxygen. is delivered to, the fetal tissues (150, 74, 75). Christianson discusses the similarity between studies of placental ratios by smoking level; altitude; maternal anemia:, and cyanotic maternal heart disease. He suggests that the changes in placental ratio represent an adaptation to relative fetal hypoxia (20). An adaptive advantage for survival might occur because a smai ler fetus would have a decrease oxygen demand. If - so, it is extremely .important to know whether this reduction in size is accompanied by any long-term. costs In later growth and development. In early studies the consistent finding that mean birth weights were lower and the frequency of births under 2,500 grams higher for women who smoked during pregnancy, than for similar nonsmokers raised the bbvious question of whether this might be due to a smoking-related reduction in gestation. This , is not the case. Studies consistently show that mean gestation is minimally reduced by maternal smoking (less than 2 days) (150, 3, 15, 164) and that birth weight is lower for Infants of smokers than for infants of nonsmokers at each gestational age (150, 16, 87, 3). The finding that maternal smoking does not cause an overall downward shift In the distribution of gestational ages, as was shown for birth weights of smokers' infants must be due to direct retardation of fetal growth. In other words, 229

these infants are small-i'or-dates rather than preterm. The type of fetal growth r-stardation associated with maternal smoking is characterized by an abnormally short crown-heel length for gestational a_;e (93, 94). Smokers' babies are smaller than corresponding nonsmokers' babies in all dimensions measured, ineluding: length, head circumference, chest circumference, and shoulder circumference (150, 32, 33, 57, 62, 66, 106, 108, 162, 10). Previous studies of these measurements at birth have inferred that birth size r-eflects the rate of fetal growth; this has been' confirmed by a definitive study in which fetal biparietal diameters were measured serially during gestation. Persson and coworkers studied 5,715 pregnancies prospectively, making ultrasonic measur-ments of biparletal diameters (BPD) from 18 to 20 weeks through term. Separate growth curves of BPD were construc-ed for fetuses of smokers and nonsmokers--who were delivered between 266 and 294 days ,after the last menstrual oeriod. The BPD increased faster in the rnonsmoking group; th-: difference from the smoking group was apparent from th--28th week and was positively correlated with the average number of cigarettes smoked (Figure 3). Measuremerts taken at birth showed that the distributions of birth weiyhts and lengths shifted downwards in proportion to the level o P smoking. Figure 4 illustrates this •shift (118). Thes-: findings corroborate Miller's characterization of smok-~rs' babies as normally proportioned but short as well as light for dates, and smaller in all dimensions than babies i-_f nonsmokers (94). The data are also consistent with the speculation that relative fetal hypoxia results in a slower rnitotic rate, a baby with fewer cells, and a reduaed oxygen demand= , Long-term_Growth and Development Possible long-term consequences of maternal smoking during pregnancy are also of auoncern. Several long-term studies provide evidence that chi_dren of smoking mothers have slight but measureable deficier.-;ies in physical growth, intellectual and emotional developmen;:, and behavior (100). Because these complex outcomes are affected by many known and unknown factors, it is important to take these other factors into accouot in any attempt to measure long- term effects of maternal smoking.' Numerous well-controlled studies have shown tha; the physical growth of smokers' 230 •

I FIGURE 3 Fetal Biparietal Diameters (BPD) values Standard Error of Means (SEM) of nonsmokers and heavy smokers (10 cigarettes/day) plotted in relation to postmenstruat age against the normal range (shaded area iepicts 95% confidence interval). mm ioo r 90 80 70 60 ,..-a 25 30 35 40 weeks

babies remains behind that of nonsmokers' babies as measured at 7 to 14 days (33); 1 year, 4 years, and 7 years (pairs of births matched for race, date of delivery, maternal age and education, and sex of child), (57); 5 years (adjusted for other factors) (162) up to 6 1/2 years (prospective study) (38); and at ages 7 and 11 (follow-up studies of the 17,000 children from the British Perinatal Mortality Study, with the adjustment for other social and biological factors) (17, 32, 36). Associations have also been noted between maternal smoking and deficiencies in neurological and intellectual development of the child. Hardy and Mellits analysed findings for 88 pairs of children of smokers and nonsmokers, matched for race, date of delivery, maternal age and education, and sex of the child. Although they reported no significant differences in intellectual function between children born to smoking "and nonsmoking mothers, the direction of difference on almost all tests was in favor of the nonsmokers' babies. Fewer smokers' than nonsmokers' children had normal neurological status at age 1, year, both in the original 88 matched pairs and . in the additional set of 55 pairs of children of smokers and nonsmokers, matched for birth weight as well as for the other cited factors. In both sets, smokers' children had lower scores on the majority of tests of intelligence and intellectual function at ages 4 and 7(150, 57). Similarly, Dunn evaluated neurological, intellectual, and behavioral status in a prospective study of low-birth-weight infants, including 76 who • were "small-for-dates" (term and preterm)', 92 "truly premature" (preterm with birth weight between 11 and 89 percerstile) and 151 full-birth-weight control infants. Neurological abnormalities, including minimal cerebral dysfunction and abnormal or borderline electroencephalograms, were slightly more common among children born to women who smoked (Table 2). In a battery of psychological tests, the mean scores of children of nonsmoking mothers were better than those of smokers' children in 45 out of 48 coerelations, and the dif- ference was significant in 14 of these. Some significant differences in favor of nonsmokers' children were also demonstrated with respect to behavior ratings and school placement (38). These results are very similar to those of Hardy and Mellits: direction of the differences was almost always in favor of the nonsmoker's child. Small numbers and population selection factors were not a problem in the 233

TABLE 2.-Incidence of neurological abnormalit,ies at about 4 1/2 years, by maternal smoking habits Percent.of Chiidren with Diagnosis tyiatenesis Maternai Smoking Habits Smoker Nonsmoker P _ _- MTnlmai cerebral dysfunction 20.0 110 <.OS . Total neurological abnormalities 29.4 19.5 <,A.S EEG borderline or abnormal Low-blrth-weight children 46.3 32.4 NS Full-birth-weight children 28.2 21.6 . NS SOURCE: Dunn, (38). 234

FIGURE 5,-Tests of 11-year-old childern by mothers' smoking habits after.'u`-e fourth month of pregnancy a) Reading w.mc-rehension 3 a 2 T-rt for differences between e 9 1 3 smoking categories after adiusting for other factors ~ 0 X ! (20.F.)-23-0: K0•001 eL 8 c 1 2 3 c$ 0 4 w 5 i e G 6 (n-6.427) (a-1.446) (n-1.097) 7 T= 0 1-9 10+ Amount smoked per day after 4th month of pregnancy b) Mathemeti a ibiiity 3 2 i O T rst for differenps between 3 smoking categories after ~ ustirg for other factors Xi (2D.F.)-59-0: P<0-W1 C Z 1 2 E- 3 o ~ ~ . c 4 3 ~ 5 ' 6 V (n-6 425) -n1.445) tn-1.097) 7- . r- -c -----r 0 1•9 10+ Amount a~,-oked per day after 4th month of pregnancy 144.5 c) Height ~ Test for differences between \ 3 smoking categories after adiusting for other factors X2 12n F_)76.2- PCn.nn1 143•5 -I 143-0 Tn'6.269) (n-1.389) (n-1.048) 0 1-0 10+ Amount _moked per day after 4th month of pregnancy ' SOURCE: Butler, A.R. (17) 236

he amount smoked within each maternal weight gain group rom less than 5 pounds to 40 pounds or more, as shown in =igure 6 (87). From Figure 4, one might conclude that smoking has a more pronounced effect on low birth weight when maternal weight gain durint pregnancy is less than 20 pounds. Other studies have Indicated a lack of relationship iretween smoking and maternal weight gain, while demonstrating a. direct relationship between »ooking and fetal growth rate. The German prospective study of 6,200 pregnant women, exam- ined every 'month from the fir it trimester through delivery, showed no significant associati~ n between smoking habit and weight gain. The usual relationships were found between smoking and small-for-dates b_,bies, with general retardation of weight, length, and head circumference in proportion to the number - of cigarettes smoked ,,uring. pregnancy (10). Miller and Hassanein also found that -;he effects of smoking on fetal growth did not appear to be related to maternal nutrition (93).. Persson's study showing retardation of fetal growth of smokers' babies by serial mea:jrement of biparietal diameters and by weight, length, and other measurements at birth showed that the low-birth-weights were independent of' maternal weight gain. These authors. •,oncluded that the fetal growth retardation resulted from a direct pharmacological effect of smoking on the fetus vrather than on influence resulting from nutritional deprivation" (118). Hajeri and colleagues studied maternal weight gain in 105 smokers of 10 or more cigarettes a day with a control group of nonsmokers who were similar with respect to gesta- tion, age, height, parity, am.l maternal weight at conception. Sirth weights, specific for ssx, were significantly higher for infants of nonsmokers, with a mean difference for boys of 330 grams and for girls of 320 grams (p<.01). Mean etrauteral weight gain, caicslated as the difference between maternal weight gain and tie weights of fetus and placenta, was 7,044 grams for smokers and 6,899 grams for nonsmokers (54). Garn has compared mean birth weights, specific for gestational age, of babies. )f obese smokers, all nonsmokers, and all smokers, using datL from' the Collaborative Perinatal Project of the National ins:itute of Neurological Diseases and Stroke (NINCDS). Obesity was defined as the top 15 percent of the distribution of pre,)regnant weights, shown separately for black and white women. i3abies of the 1,383 obese white smokers had mean birth w-:ights similar to the total group of 238

.-»....:.-:-....-~~ •FIGURE C>,- Percentage of birth weights under 2,500 grams by maternal smoking level within materal weight gain group (five-pounds intervals/ by hospital pay staus. Birth of 38+ weeks gestation. PRIVATE HOSPITAL STATUS II NON-SMOKER C s1 PACK/DAY ® 1+ PACK/DAY 0.4 5-9 10-14 15-19 20 24 25-29 30•34 35-39 40 MATERNAL WEiGHT GAIN (pounds) PUBLIC HOSPITAL STATUS rM 0-4 5-9 10-14 15-19 20-24 25-29 30•34 35-39 40+ MATERNAL WEIGHT GAIN (pounds) r

white nonsmokers and higi er than the total group of white smokers. The 1,001 obese black smoking mothers had babies whose mean birth weights °.vere generally higher than those of all black nonsmokers, leadi ig Garn to conclude that "maternal obesity (weight-defined) apparently counteracts the smoking effect, on the conceptus" (47). Because birth weight is strongly correlated with :naternai size, a more appropriate comparison would have b=-in between mean birth weights of the' babies of obese smokers and the babies of obese nonsmokers. That such a comparison would show, the usual relationship to maternal smoking level is suggested by Meyer's analysis of •birth weight by maternal smoking and prepregnancy weight (Table 3). The correlation between maternal weight and the proportion of lo-.e-birth-weight babies is clear at each smoking level, and the independent relationship between smoking._levei and low-birt-4 -weight is clear at each level of inaternai weight. The relative increases in the proportionf of low-weight births with ' light and with heavy smoking are almost identical in the ioree strata of prepregnant weight (90). . Studies of birth weight, maternal weight, and maternal weight gain should also be carefully controlled for maternal age and parity. In studie-; of successive births to the same mother included in the Collaborative Perinatal Project of the NINCDS, Garn found pre;iregnancy weights increased with successive pregnancies by similar amounts for smokers and nonsmokers (48). Naeye, ising the same data base, reported that maternal weight gain was less in the second pregnancy than in the first pregnancy for smokers, for nonsmokers, and for women who changed habits between pregnancies in either direction (110). Second :iabies weighed on the average 24 grams more than first o.~bies If the mother smoked both times, and 32 grams more if the mother smoked neither time (Table 4). If the mother smoked during the first and not during the second pregnai-mcy, the second baby weighed an average of 110 grams more than the first baby, whereas the second babies of women who smoked during the second pregnancy but not during the first pregnancy averaged 58 grams less than their first babies (97). The most careful atalyses •indicate that the effect of maternal smoking is a direct one not mediated through an effect on maternal appetite, eating, or weight gain. In conclusion, as stated in a1,ancet editorial, "the appeal of the nutritional hypothesis is t;iat women might be more readily encouraged to eat more -luring pregnancy than discouraged 240 *

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, f + .; from smoking.... However, if, as now seems more likely, the growth-retarding effect of smoking is due to fetal hypoxia, there is no short-cut to removing this adverse influence" (68). This conclusion in no way obviates the enormous importance of dietary factors during pregnancy. Overt maternal malnutrition is associated with inade- quate growth. Recently, it has been suggested that more subtle alterations in the maternal supply of essential nutrients combined with compromised uteroplacental circulation may contribute to reduced fetal growth. Crosby, et al. (28) observed that the concentrations of each of 14 amino acids and carotene were reduced significantly in the blood of smoking mothers. These workers postulated that, while these differences were on the order of 10 or 20 percent, they could be an important factor in producing the small-for- gestational-age infants associated with maternal smoking. In a study of over 1,100 pregnant women, Schorah, et al. (139) noted an Inverse correlation between the number of cigarettes smoked and the leucocyte ascorbic acid concentration. For instance, the leukocyte ascorbic acid concentration was about 22 percent less In the blood of women who smoked more than 20 cigarettes a day as compared with controls.. Despite a 15 percent increase in the number of circulating leucocytes in the blood of smokors, the blood ascorbic acid concentration was still 10 percent less than in controls. These differences were even more marked in women from lower socioeconomic groups. The authors suggested that in addition to the role of ascorbic acid in fetal nutrition, these lowered concentrations might be related to the increased incidence of premature rupture of the amniotic membranes in smoking women. SMOKING, FETAL AND INFANT MORTALITY, AND MORBIDITY Spontaneous Abortion Past studies have demonstrated a statistically significant association between maternal cigarette smoking and spon- taneous abortion (60, 66, 89), some showing a strong dose- response relationship (114, 148, 167). Spontaneous abortions are difficult to study because of problems of ascertainment. In prospective studies, early abortions may be missed, and bias may occur if one group tends to register earlier than the other. Retrospective studies allow more complete ascertainment but are subject to errors of recall. Nevertheless, higher rates of spontaneous abortion have been 243 TIm 0048461

associated with maternal smoking. in both types of studies (66, 89, 167).. ~_ Kullander and Kallen found higher rates of "spontaneous abortion" among smoking women, but noted that many of these pregnancies were unwanted. Analysis of their data showed that the relative risk of spontaneous abortion of smokers compared with nonsmokers was 1.20 for wanted and 1.35 for unwanted pregnancies (66). A case-control study of spontaneous abortion, with important variables held constant reported an 80 percent increase in the odds of smoking among the cases compared with controls (65). Recent studies corroborated the finding of associations between smoking and spontaneous abortion risk. In a small retrospective study in New Zealand, ' Fergusson found that women who smoked more than 20 cigarettes a day had almost twice the nonsmoker risk of having had a previous spontaneous abortion, and that the association could not be explained by differences in maternal age, educational level, parity, race, socioeconomic status or marital status (46). In a study of 12,013 consecutive pregnancies in Dublin, Ireland, Murphy and Mulcahy found a positive association between the number of cigarettes smoked and the rates of spontaneous abortion, independent of the. effects of maternal age and parity. The authors stated that induced abortions are a negligible factor in Ireland and concluded that maternal smoking leads to reduced reprod;uction efficiency at all stages of pregnancy (96). Himmelberger and colleagues surveyed a group of professional women in medicine concerning the influence of maternal smoking on their 12,194 pregnancies (59). After controlling for interfering variables, the risk of spontaneous abortion for certain subgroups of heavy smokers was estimated to be as much as 1.7 times that for the nonsmoker. Spontaneous abortion rates were lowest in the 25 to 29 year old category, increasing with age to levels of 33 and 36 • percent for nonsmokers and smokers, respectively, at age 40 plus. The relative increase in risk associated with maternal smoking was highest at the youngest ages below 25 years and decreased with increasing age (59). An editorial in the Sritish Medical Journal summarized these findings and stated: "Cigarette smoking, one of the first manifestations of women's social emancipation, is emerging as a possible threat to her procreative role." The proportion of abnormal karyotypes in abortuses of women who smoke appears to be reduced rather than increased (17). The mechanism underlying the smoking-related excess appears to 244 TIMN 0048462

be due to compt.ications of pregnancy rather than to any fetal abnormality (13). Congenital Malformations 4 Several studies have reported perinatal, fetal, or neonatal ~ mortality rates by cause. In these comparisons, death rates ~ due to congential malformations have usually been lower for smokers' than for nonsmokers' infants (3, 24, 51, 91). This Is compatible with the finding that smoking-related spontaneous abortions include a lower frequency of abnormal karyotypes and tend to occur later than spontaneous abortions in nonsmokers. As previously described, increased losses of conceptus associated with maternal smoking appear to be due to pregnancy problems and complications rather than to abnormalities of the embryo or fetus (45). Andrews and McGarry, in a community study of 18,631 pregnancies in Cardiff, Wales, reported that smokers' infants had lower mortality rates from malformations than those of nonsmokers. The rates of congenital malformations resulting in stillbirths was 0.32 and 0.27 and resulting in neonatal deaths neonatal deaths were 0.33 and 0.31 per 100 births of nonsmokers and~ smokers, respectively. On the other hand, the incidence of congenital malformations among all single births in Andrews' population was higher among smokers' babies, overall, and specifically higher for cleft palate and lip. Among other sites, some were higher for smokers and some for nonsmokers, as Is shown in Table 5 (3). A significant positive association between cardiac malformations and maternal smoking was shown by Fedrick and colleagues, based on firm diagnoses among stillbirths, neonatal e 7 from the British Perinatal urvivors to a d th d g an s t ea s, Mortality Survey. However, this difference was largely due to ' the inclusion of patent ductus arteriosus, which may or may > not be classified as a malformation (47). Some recent studies have shown a positive association ~ between maternal smoking and congenital malformations, ! defined in a variety of ways. Himmelberger and colleagues ; carried out a mail survey of professional women in medicine (59). They were interested in exposure to anesthetic gases in ' the operating room, and evaluated possible effects on ` pregnancy outcome of a number of factors including cigarette . smoking. Information was obtained and analyzed by a multiple logistic regression based on 12,914 pregnancies, including 245 r TIMN 0048463

TABLE S.-Incidence of congenital abnormality (all single births) Non-smokers Smokers Number Percent Number Percent Total abnormal Infants 2.37 2.73 Type of abnormality Anencehaly 18 0.2 15 0.2 Spina bifis 20 0.22 23 0.3 Other C.N.S. abnormality 38 0.42 36 0.47 CVS abnormality 34 0.37 32 0.42 Cut abnormality 21 0.23 24 0.32 Genito-urinary abnormality 39 0.43 25 0.33 Bone abnormality 65 0.72 52 0.68 Cleft palate and/or hare lip 10 0.11 20 0.26 Other abnonnality 19 0.21 18 0.24 x2(all abnormalities) = 2.22, p= >).)%. x2(cleft palate and hare lip) 3 5.36, p.= >0.01. SOURCE: Andrews, J. (2). 246 TIMN 0048464

, r r i J 1 . 10,523 live births, which represented a response rate of 53.2 percent. After the effects of age, exposure to anesthetic gases, and pregnancy history were controlled, the risk of congenital abnormalities for babies of mothers who smoke was estimated. A statistically significant risk (p<.05) for maternal smoking was found. Figure 7 shows the risk of congenital abnormality as a function of maternal age for nonsmokers, moderate smokers (1 to 19 per day), and heavy smokers (20 plus per day). Relative risks for heavy smokers compared with nonsmokers were as high as 2.3. Rates of abnormalities in each general category were higher for the children of smokers (see Table 6). The significant increase in cardiovascular abnormalities among smokers' children is in agreement with Fedrick's findings (44) and in general agreement with the study of Andrews and McGarry (3). Himmelberger, et ai. do recognize that their findings are based on retrospective survey data, obtained by mail, and therefore subject to bias from various sources, including that of a highr nonresponse rate. However, the study methods have been designed to eliminate those effects (159). A recent study. by Borlee and Lechat controlled for confounding variables by matching births with congenital malformations to control births according to hospital and time of birth, maternal age, sex of child, and socioeconomic level' of parents. Two hundred and two children with malformations diagnosed at birth were compared with 175 controls, from a total of 17,970 consecutive births studied from June 1972 through May 1974. No differences were' found between cases and controls in the distribution of smoking habits, including the number of cigarettes smoked with or without filters. Sixty-six percent of mothers of malformed infants and 68 percent of mothers of controls were nonsmokers. Fathe.rst smoking habits were also similar among cases and controls. Significantly more mothers of malformed infants were heavy coffee drinkers (8 plus cups per day). Because of the frequent association between heavy coffee drinking and smoking, both habits should be included in studies of environmental factors possibly related to the risk of conge- nital malformations (10). The same is true for consumption of alcohol in populations where drinking is prevalent. Mau and Netter have reported births by gestation, birth weight, perinatal mortality, and the incidence of congenital malformations by smoking habits of fathers in 3,696 cases in which the mother was a nonsmoker. Trends toward lower birth weights and more preterm births with increasing levels 247 TIMN 0048465

FIGURE 7.- Risk of congenital abnormality according to age and smoking habit ~ .09 ~ 08 a •. .~ c ~ .07 -••., .. /tieavy Smoker y A3 0 18 , 22 26 30 34 38 42 46 50 Materna( Age SOURCE: Himmelberger, O.U.(59) 24' ~IMN 0048466.

s e a TABLE 6.-Comparison of contenital abnormality rates for babies born of smokers and nonsmokers, by type of abnormaiity. Y 7 i Abnormality Smokers Nonsmokers Ps ~ 96 No. 96 No. Cardiovascular- 19.07+ (68) 13.65 (95) 0.02 , s Respiratory 15.15 (54) 12.07 (84) 0.10 , t . Musculoskeletal 23.84 (8s) 19.69 (137) 0.08 :.~ Gastrointestinal 13>46 (48) 9.48 (66) 0.04 : Central nervous system 11.50 (41) 10.20 (71) 0.27 a Urogenital 21.32 (76) 1S.a1 (110) 0.02 'One-tall significance level for the test of the difference between two proportions. +Rate is number of congenital abnormalities per 1,000 live births. Rates based upon 3,565 live births amon$ the smokers and 6,958 live births amon; the nonsmokers. SOURCE: Himelber=er, et ai. (59). 1 ! TIMN 0048467

of paternal smoking were not statistically significant. In the total study of 5,200 births, rEgardJess of maternal smoking habits, ' there was a• significaet ' increase in the incidence of several malformations with increasing levels of paternal smoking; children of heavily smoking fithers had about twice 'the, expected Incidence. Although malformations in all systems wer¢ more frequent if the father smoked over 10 cigarettes per day, only the differences in facial malformations were significantly different (p<.01) by smoking level. The authors state that the trends with paternal smoking were Independent , ._ ~ . - ~ - -~ of maternal smoking level, maternal ' and paternal age, and social class (84). More studies of these possible relationships are urgently needed.As serious malformations •are relatively rare, the case-control approach Is probabiy the method of choice, with careful matching of cases with suitable controls. Perinatai Mortality 132, 148, 164). Table 7 illustrates these points. It shows that women eharaeterized by low social class, low .level of education, being very young or • old during pregnancy, or being black, have higher risks of perinatal mortality than their coun- terparts. . Their increase in risk due to smoking is relatively greater. Meyer, et ai. measured the perinatal mortality risks of light smokers (less than a pack of cigarettes per day) and of heavy smokers (one pack or more per day) relative to nonsmoker risks within subgroups of the population (110, 111). The increased risk of perinatal mortality for light smokers who were young, low-parity, and non-anemic was ie~ss than 10 percent. At the other extreme, mothers characterized by high-parity, public hospital status, previous low-weight There is a direct relationship between level of maternal smoking and the risk of perinatal Joss (150, 151). , There were two important reasons for variability bet- n ween studies on perinatal. loss and smoking. - First, other important variables such as age, parity, race, and socioeco- nomic status Influence the results if they, are unequally distributed between comparison groups of smokers and nonsmokers' (89). Second, cigarette smoking is more harmful to the pregnancies of certain women than to those of others. In general, women with other- risk factors were at greater k risk from smoking than otherwise low-risk women (3, 16, 24, 250 TIMN 0048468

births, or anemia had an increased perinatal mortality risk of 70.to 100 percent when they were heavy smokers (92). To help visualize the interacting effects of maternal smoking and of other factors on perinatal mortality risk, Butler has calculated theoretical mortality risks based on data from the British' Perinatal Mortality Study. In Figure 7, perinatal mortality risks by social class, maternal age, and parity are arranged in order of increasing magnitude. The differences between smokers+ and nonsmokers' risks are represented by the height of the bars, which varies depending on other risk factors (16). . These studies show that the risk of spontaneous abor- tion, of fetal death, and of neonatal death Increases directly with increasing levels of maternal smoking during pregnancy. Studies of smoking during pregnancy show a range of perinatal mortality risk ratios (smokers versus nonsmokers) from a low of 1.01 to a high of 2.42. Cause of Death The Increased perinatal mortality associated with maternal smoking is concentrated within . a few cause-specific cate- gories. Excess stillbirths have -been associated with ante- partum hemorrhage or abruptio placentae and with "unknown cause (3, 51). Excess neonatal deaths were associated with Immaturity, asphyxia, atelectasis (25), and with the respiratory distress syndrome (3). Meyer and Tonascia (91) analyzed fetal and neonatal deaths to identify causes of death which showed an excess if the mother smoked. Fetal and neonatal deaths by coded cause and maternal smoking habit are shown in, Table 8. For each cause the observed numbers for smokers were compared with the number expected at nonsmoker rates. The differences between observed and expected numbers indicate the number of deaths In each category attr,ibutable to maternal smoking. Fetal deaths showed a major smoking-related excess in the category of "unknown" cause and some increase from "anoxia" and "maternal cause." By contrast, neonatal deaths ielated to smoking were in the category of "prematurity alone,1 or In the related category of "respiratory difficulty." The tentative conclusion to be drawn here is that fetuses and neonates whose deaths were related to maternal smoking had ,no recognizable pathology, but had died in utero from anoxia, maternai cause, or unknown cause, or had suffered the consequences of preterm delivery. 252 TEAN 0048469

r 0 TABLE 7.-Examples of Perinatal Mortality Smoking Status Related to Other Subgroup Characteristics Y No. of births Perinatal or neonatal deaths 1,000 births Relative Study Population Non- Smokers Smokers Category Non- smokers Smokers risk• British Perinatal Mortality 11,145 4,660 Social class Survey, England, all 1,2 (high) 25.8 26.3 1.02 births 3-5 33.5 46.6 1.39 Washington Co. Maryland, 7,646 4,641 Fatherls white education 9+ years 14.4 16.1 1.12 <8 years 17.6 38.0 2.16 N ~ Northern Finland, white 8,898 2346 23.2 23.4 1.01 California, middle to Race upper middle class 6,067 3,726 White 11.0 11.3 1.03 2,219 1,071 Black 17.1 21.5 1.26 Boston City Hospital Race Prenatal Clinic 513 892 White 29.2 31.4 1.08 1,225 1,071 Black 28.6 54.1 1.26 Quebec, 10% Sample of 3,912 2,967 Maternal age registered births <25 12.1 16.1 1.33 25-34 12.6 13.2 1.05 35+ 23.0 41.7 1.81 •Ratio of-mortality rate for smokers' to nonsmokers' babies. Neonatai only. cn mrr-• n4.v- M n IR91.

COMPLICATIONS OF PREGNANCY AND LABOR t : Studies have consistently found a direct relationship between maternal smoking level and the Incidence of placenta previa, •abrupt.io placentae, bleeding during pregnancy, and premature rupture of membranes (3, 26, 51, 66, 90, 91, 98, 100, 134, 148, 149). The association is independent of socioeconomic and racial background (148), parity (3) and many other factors (9.0) (Figure 8). These complications carry with them a high risk of fetal and neonatal loss, and are frequently cited as the cause of death among the offspring of women who smoke. Kullander and Kallen found a significant increase in the frequency of abruptio placentae among smokers' children dying -before the age of 1 week (66). In a prospective study of 9,169 pregnancies- by Goujard and colleagues, a large proportion of the increase in stillbirths among smokers was caused by abruptio placentae (51). Naeye reviewed the clinical and postmortem material from the 3,897 fetal and infant deaths in the Collaborative Perinatal Project of the NINCDS (106) and reported an asso- ciation between perinatal mortality rates caused by abruptio placentae and number of cigarettes smoked by the mother (100). Abruptio placentae was the underlying cause -identified ' -in' 11 percent of all the deaths In this large study (98). Analysis of data from the Ontario Perinatal Mortality Study corroborated these findings. Increasing levels of smoking resulted in a highly significant increase in the risks ' of placental abruptions, plicenta previa, bleeding in pregnancy, and premature and prolonged rupture of membranes. Fetal and neonatal deaths were analyzed for associations between them and smoking-related excesses of various coded complications of pregnancy and labor. Although most diagnoses showed no association with ecess mortality for smokers' babies, a few stood out as highly . significant. Excess fetal deaths of smokers' babies we're strongly associated with bleeding during pregnancy, either before (p=0.01) or after (p=0.0005) 20 weeks' gestation. In other coded categories, a significant excess of fetal deaths occurred among smoking mothers with abruptio placentae (p=0.0001) or other obstetrical problems. Similar comparisons were made for neonatal deaths. A strong, significant relationship between smoking-related excess neonatal deaths and a history of bleeding before 20 weeks of gestation was found (p=0.0001). Other categories that showed significant increases of smoking-associated neonatal deaths 254 TIMN 0048471 -

~ FIGURE 8: Theoretica! cumulative mortality risk according to . smoking habit, in mothers of different age, parity, and social class groups. , Soeial elasa S 400 1&2 ' Q 3 i ~ -4&5 s ~ 30 Theoretical s Mortatity t Risk i e .. . a ` . 20 S ) d 10 + 4 , Para 12.3 Para 0 Pan 4+ Para1.2.3 Para 0 Para 4+ Under 35 years 35 years + 0 1 SOURCE: Butler, N.R. /16) 255 - t..;. maker Non Smoker TIMN 0048472

were the admission status of rupture of membranes only, other obstetrical complications, and duration of rupture of membranes over 48 hours (91). Pteeclampsia Some of these studies have shown an inverse dose-response relationship, with the Incidence of preeclampsia declining as the number of cigarettes smoked increased (113, 149). Data from the British Perinatal Mortality Study were cross- tabulated by parity, severity of preeclampsla, and maternal smoking status. Smokers had lower rates of all grades of preeclampsia than nonsmokers, whether they were primiparae or muttiparae (16). Andrews and McGarry showed that the Inverse relationship between cigarette smoking and preeclamptic toxemia was independent of social class, maternal weight before pregnancy, and maternal weight gain during pregnancy (3). Despite the effect of smoking on the inci- dence of preeclampsia, there is a greatly increased risk of perinatal mortality If preeclampsia does develop in a smoker (3, 37, 133). Several authors have suggested that this negative association may be due to the hypotensive effect of thiocyanate, which is derived from the' cyanide present in cigarette smoke and Is regularly found in the blood of smo- kers (3, 113). Because preeclampsia is predominantly a complication of first pregnancies, it Is possible that the occasional finding of reduced rates of perinatal mortality In young, primiparous, light smokers who are otherwise healthy Is due to this relationship. Perani and MacGillivray performed seven serial measurements from the end of the second trimester until term . in 31 nonsmokers and 29 smokers. After 25 weeks gestation the plasma volume of smokers failed to keep pace with that for nonsmokers, the increases in volume being 25 percent less in smokers (Figure 9). Plasma volume and total body water expansion are related to birthweight, at least in primigravidas. After 30 weeks of gestation, total body water in smokers plateaued in contrast to nonsmokers, so that by term their body water volume Increase was about 25 percent less. Serum heat-stable alkaline phosphatase levels in smokers significantly exceeded the concentration in nonsmokers from the 37th week of pregnancy onward. This enzyme is of placental origin, and cigarette smoking may contribute to this change by its effects on the placenta (121). 256 TIMN 0048473

FIGURE 9-Mean•plasma volume in nonsmokers and smokers. ~ ® ` ~ ~ d a t r i 4.0 3.5 3.0 2.5 SOURCE: Pirani & MacGillivray (121) 257 TjMN 0048474 .

Whether the reduction in the incidence of preeclampsia with maternal smoking Is due to the hypotensive effects of thioeyanate, to the reduced size of the baby, to a smaller inerease in maternal blood volume, or to another process requires further study. , Preterm Delivery, Pregnancy Complications, and Perinatal Mortality by Gestation Studies of large numbers of births to measure mean gestation by smoking habit have demonstrated differences of only a day or two. This finding led to ihe conclusion that maternal smoking does not affect gestation, (150, 15, 57, 78, 106, 164).. On the other hand, abundant evidencehas been pre- sented that a smoking-related increase in preterm delivery plays an important role in the increased risk of neonatal death for infants of smokers. When the proportion of preterm births is measured, rather than the mean gestation, smokers have shown con- sistently higher rates than nonsmokers, as illustrated in Table 9. In four studies in which all. births and perinatal deaths were Included, the risk of early delivery Increased from 36 to 47 percent If the mother smoked, and 11 to 14 percent of all preterm births could be attributed to maternal smoking (3, 16, 42). Figure 10, using data from the Ontario Perinatal Mortality Study, shows percentage distributions by gestational age of births to nonsmokers, light smokers, and heavy smokers, plotted on a semilogarithmic scale to emphasize differences between smoking-level groups in very preterm births. There Is little difference between the means of these curves because the great majority of births occur around term in all groups. There Is, however, a significant and dose-related increise in the proportions of preterm babies born to women who smoke. These, preterm deliveries account for a small proportion of total births but for a large proportion of the deaths (150, 86). As previously reviewed, Meyer and Tonascia have related the excess fetal and neonatal mortality of smokers' infants and the . excess incidence of pregnancy complications among women who smoke to the gestational age of occurrence, using a life-table approach. A starting population of all pregnancies In utero at 20 weeks was used to calculate the probabilities of fetal death, live delivery followed by survival 258 TIMN 0048475

J TABLE 9.-Preterm births by maternal smoking habit. Relative and attributable risks, derived from published studies Smokers Preterm Births# per 100 Total Births Relative Risk Smokers/Non- Attributabie Risk Study (proportion) Nonsmokers Smokers smokers 96 Cardiff .465 6.7 9.2 1.36 14 Great Britain .274 4.7 6.9 1.47 11 Montreal .432 7.7 10.6 1.38 14 Ontario .435 7.4 10.1 1.36 14 *Cardiff and Ontario data are for <38 weeks. All others are'for <37 weeks. SOURCE: (150, 3, 16, 42, 90).

FIGURE 10.-Percentage distribution by weeks of gest- ation of births to nonsmokers, smokers of less than one pack per day, and smokers of one pack per day or more. 60A-}- 40.0 + 20.0+ 10A4- 2A4- 0.6 -1- 0. + 0.1 I ~ ~- ! _i t 1 1 i t r ii i T_~ 20 24 28 GESTATION: WEEKS i 1 i 4 . 7 i 80.0 T 32 36 40 44+ SOURCE: Meyer, M.B. (86) 260 I 4 I

: I : . , . t t i , > ; or death, or the occurrence of a compiication followed by fetal death or delivery. At 28 weeks (the next point defined by the data), the population at risk included those remaining in utero at that point.. Figure 11 shows the probability of perinatal death during each period of gestational age starting at 20 weeks. Risks for smokers' infants were significantly greater in the earlier weeks, but not different after 38-week gestation (150, 91). A similar approach was applied to determine the risk by gestation of abruptio placentae, placenta previa, and premature rupture of membranes for smokers and nonsmokers. The risk of all these complications was higher for smokers throughout gestation, but In all, the differences were most significant in the weeks of pregnancy from 20 to 32 or 36 weeks (150, 91). The lower limit of 20 weeks was built into the study design, which included al l single births 'of at least 20 weeks gestation (110, 111). These studies show that excess deaths of smokers[ infants are found mainly in the coded cause categories of "unknown" and "anoxia" for fetal deaths, and in the cate- gories of "prematurity alone" and "reespiratory difficulty" for neonatal deaths. This finding indicates that the excess deaths result not from abnormalities . of the fetus or neonate, but from problems related to the pregnancy. Increasing levels of maternal smoking result in a highly significant increase in the risks of placental abruptions, placenta previa., bleeding early or late in pregnancy, premature and prolonged rupture of membranes, and preterm delivery, all of which carry high risks of perinatal loss. Although there is little effect of maternal smoking on mean gestation, the proportion of fetal deaths and live births that occur before term increases directly with maternal smoking level. Up to 14 percent of all preterm deliveries in the United States may be attributable to maternal smoking. According to the results of one large study, the most significant difference between smokers' and nonsmokers' risk of perinatal mortality and pregnancy complication occurs at the gestational ages from 20 to 32 or 36 weeks. These findings lead to the conclusion that maternal smoking can be a direct cause of fetal or neonatal death in an otherwise normal infant. The immediate cause of most smoking-related fetal deaths is probably anoxia, which can be attributed to placental complications with antepartum bleeding in 30 percent or more of the case5'. In other cases, the oxygen supply may simply fail from reduced carrying, capacity 261 . - TIMN 0048478

FIGURE 11-Probability of pernatal death for smoking and nonsmoking mothers, by period of gestational age. Bars show 95% confidence intervals. NONSMOKERS SMOKERS TOTAL BIRTHS 27420 21485 TOTAL DEATHS 634 624 PROBABLITY OF DEATH 023 029 2 W 0'1 'L j 95% CT c o L j~ Q 0.04 ~-• ¢ z 0.02 ~ 0.004 ~ W a U. 0 Y 0.01 0.000 0.001 0.002 0.001 TotalDeaths 283 198 121 110152149 187 78 1Smok.n 6 20 24 28 32 36 40 42 Nonunokars GESTATION WEEKS SOURCE: Meyer, M.B. (91) 262 • TIM~T 0048479

and reduced unloading pressures for oxygen caused by the presence of carbon monoxide in maternal and fetal blood... Neonatal deaths "occur as a result of the increased risk of early delivery among smokers, which may be secondarily related to bleeding early in pregnancy and premature rupture of membranes (150). . • LONG-TERM MORBIDITY AND MORTALITY Studies of infant and child morbidity and mortality by the mother's smoking habits usually cannot distinguish between the effects of smoking during pregnancy 'and the effect of the infant's or child's passive exposure to cigarette smoke after birth. Several studies have found that hospitalization rates for pneumonia and bronchitis were higher during the first year of life for infants of smoking mothers (22, 23, 58). Rates in children were higher if the smoking parents also had cough and phlegm. Harlap and Davies found that the risk of contracting pneumonia or bronchitis in the first year of life more than doubled if the parents smoked more than 24 c igarettes a day (58). A un.ique and important study of morbidity and mor- tality in smokers' and nonsmokers' children up to the age of five has now ' been published by Rantakallio (123). The experience up to age 5 of over 12,000 children born in 1966 in Northern Finland, comprising 96 percent of all births in two provinces was ascertained through hospital and death records and questionnaires. Smoking was rare in this popu- lation, and the smokers tended to be young and otherwise healthy. Fourteen percent of pregnant women smoked fewer than 10 cigarettes per day (mean number after the second month of pregnancy 3.9) and 3 percent smoked more than 10 cigarettes per day (mean number 12.2);. the remaining 83 percent of the7 population were nonsmokers. It was therefore possible to remove the usual problems of confounding variables by close Individual matching of 1,750 smokers to nonsmoking "eontrols". Matching factors included marital status, maternal age within 2 years, and place of residence, with the latter category including many socioeconomic variables to equalize the probable use of medical facilities and other differences. Although the author states that perinatal mortality. did not show a statistically significant increase for smokers, rates were 24 per thousand for controls, 26 per thousand for light smokers, and 33 per thousand for "heavy" smokers (defined as 263 TIMN 0048480

, smoking 10 plus cigarettes per day). These rates are similar to those found in other studies in which differences were statistically significant. Postneonatal -mortality, from 28 days to 5 years, was higher for smokers' children with rates of 11.1 and 3.9 per thousand for smokers' and nonsmokers' children respectively. Overall death rates of 24.7 per thousand births in smoking women and 16.5 per thousand births in nonsmoking women were reported for children under the age of 5, of which 12.6 and 8.8 were neonatal. In addition, the children of the smokers were hospitalized more frequently, had more visits to doctors, and had longer average durations of hospital stays than chi(dren of nonsmokers. Respiratory diseases caused significantly more hospitalizations among smokers' children. It is of great interest that the children born to a subgroup of women who stopped smoking during the last 3 months of pregnancy showed no Increase of postneonatal mortality or morbidity up to the age of 5, compared with controls. However, these women had been very light smokers before quitting. Table 10, derived from Rantakailio's study, shows that the various outcomes measured show inereasing rates of morbidity and mortality with increasing levels of smoking. However, it may not be possible to distinguish between the adverse effects of maternal smoking during pregnancyd ind the adverse effects on infants and children exposed to cigarette smoke in the home, because women who smoked during pregnancy probably also continued to smoke after pregnancy. Because of the known carcinogenic potential of tobacco smoke and the evidence that benzo(a)pyrene reaches the pla- centa, Neutel and Buck investigated the relationship of maternal smoking during pregnancy to the incidence of cancer in children aged 7 to 10. A combined population of 89,302 births from the Ontario Perinatal Mortality Study and the British Perinatal Mortality Survey was used as a base popu- lation for a prospective study in which 65 cancer deaths and 32 cancer survivors were identified. For cancer of all sites, the children of smokers had a relative risk of 1.3, with 95 percent confidence Aimits of 0.8 to 2.2. A dose-response relationship was not observed. The numbers were not large enough to determine significant differences by site. Excess cancer rates for children of mothers who smoke and a possible dose-related progression were concentrated at ages 0 to 24 months, but these rates were based on smal i numbers of cases. The authors conclude that "although a significant excess is not demonstrable, a doubling of the cancer risk for 264

TABLE 10.-Long term effects on morbidity and mortality by level of maternal smoking Rantakallio Data A. Morbidity Nonsmoker Light Smoker Heavy Smoker Control 1 Control 2 (1-10 per day) (10+ per day) Number of ChUidren 1300 258 1302 252 Doctor visits per child (mean number) .71 .61 .76 .83 Hospitalizations per child (mean numbet) .19 .15 .22 .39 <Age 1 .14 .08 .17 .30 Age 1-5 .15 .17 .22 .25 N ~ ~ B. Perinatal and Postneonatal Mortality (28 days to 5 years) Per 100 Births, by Maternal Smoking 'Nonsmokers Smokers Control Light' Total Heavy Total Births N. , 1844 1844 Perinatal Mortality per 1000 Births 23.9 25.7 32.6 Postneonatal mortality 3.9 11.1 All mortality per 1000 live births 16.5 24.7 i SOURCE: Rantakalllo, (124).

children of smokers cannot be ruled out." Their equivocal results were reported to encourage other workers to add to the data (103). This should certainly be done, with particular emphasis on the first 2 years of life. Rantakailio, et al. also analyzed the use rates of ophthalmological services in their follow-up study of approximately 12,000 children, relating these rates to prenatal factors ascertained during pregnancy. The incidence of squint among smokers' children was 22.5 per thousand, compared with 11.5 per thousand among the children of matched, nonsmoking controls (p<.05). On the other hand, rates of dacryostenosis and of other congenital ocular malformations were higher among the children of controls. The authors state that squint was inversely correlated with birth weight and was more common among children with other diseases, especially nervous or mental diseases (124). Sudden Infant Death Syndrome Maternal smoking habits have been ascertained in several studies of the sudden infant death, syndrome (SIDS). In all of these, an association has been found between maternal smoking during pregnancy and the incidence of sudden Infant death. Steele and Langworth, in a study of 80 cases, each with two matched controls, which were traced back to the Ontario Perinatal Mortality Study population of 1960-61, found that sudden infant deaths were strongly associated with the frequency and level of maternal smoking during pregnancy (p<0.001). Thirty-nine percent of the cases were nonsmokers versus 60 percent of controls; 36 percent of the cases and 27 percent of the controls smoked less than a pack per day; 24 percent of the cases and 10 percent of the controls smoked a pack per day or more. The habits of• the remaining 1 to 2 percent of mothers were unknown (143). Bergman and Wiesnor studied 56 families who lost babies to the sudden infant death syndrome and 86 control families. They reported that a higher proportion of SIDS mothers smoked during pregnancy than controls (61 percent versus 42 percent), more smoked after pregnancy (59 percent versus 42 percent), and SIDS mothers smoked a significantly greater number of cigarettes than controls. These authors indicate that exposure to cigarette smoke (passive smoking) appears to enhance the risk for SIDS for reasons not yet known (9). However, whether prenatal or postnatal exposure 266 T'IMN 0048483

is more important cannot be determined. Naeye, et• al. in their analysis of 125 SIDS victims from the population of the Collaborative Perinatal Project of the NINCDS, stated: "The gestations that produced the S1D5 victims were characterized by a greater frequency of mothers who smoked cigarettes and had anemia" than was true for the whole population of 53,721 infants or for a set of 375 controls matched for important factors (99). Rhead, commenting on studies published to date which demonstrate an Increased incidence of maternal cigarette smoking in SIDS, states: plt is now...clear that maternal cigarette smoking contributes to an infant's risk of dying from S1DS" (127). MECHANISMS Clues to the mechanisms by which smoking may Increase the risk of pregnancy complications are available from pathological and physiological studies of placentas, membranes, blood vessels, circulatory patterns, and serum levels of substances Important for cell and tissue integrity. For example, it is possible that placental changes in smokers that serve as adaptations to the hypoxic effects of carbon monoxide may also Increase the risk of placental complications. Christianson has reported findings from carefully standardized gross examinations of 7,651 placentas from smo- kers and nonsmokers. These examinations revealed that smokers' placentas were thinner and larger in their minimum diameter than those of nonsmokers. This significant change effectively inereased the surface area of the smokers' pla- centas and must, therefore, have increased their area of attachment to the uterine wall. The distance from the edge of membrane rupture to the placental margin was also less for smokers, and significantly more smokers than nonsmokers had zero distance, which is consistent with the diagnosis of placenta prevla (20). These findings suggest a possible mechanism to account for the significant dose-related increase In the frequency of the clinical diagnosis of placenta previa that accompanies maternal smoking (90). A similar increase in this condition occurs with increasing altitude (79). Christianson's study also revealed that smokers had significantly more placental calcification, primarily of the maternal surface, and patchy subchorionic fibrin, as shown in Table 11. These changes are characteristic of maturation and aging of the placenta and occur as normal gestation proceeds; 267 TIMN 0048484

TABLE 11.-Selected results of gross examinations of placentas from smokers and nonsmokers Percent of Placentas with Stated Condition WH I TE BLACK Nonsmoker Smoker Nonsmoker Smoker N=3,461 N=2,238 P N=1,300 N=652 P Calcification 49.5 60.8 <.0001 43.5 59.0 <.0001 Patchy Subchorlonic Fibrin 26.2 35.3 <.0001 30.8 37.0 <.01 Infarcts 24.6 22.3 <.05 14.4 14.5 NS - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Thickness (mean cm) 2.6 2.12 <.001 2.11 2.06 <.01 N Ratio of smallest diameter to thickness 8.19 8.40 <.001 8.39 8.68 <.01 ~ Shortest distance, edge of rupture of membranes to placental margin (mean cm) 4.32 4.09 <.025 5.08 4.83 NS Percent with zero distance 25.6 27.9 NS 18.6 20.3 <.05 SOURCE: Christianson, (20).

however, they occurred earlier in smokers than in nonsmokers (20). This finding Is compatible with other manifestations of accelerated aging reported to be associated with cigarette . smoking (112, 30). Asmussen compared placental vessels in smoking and nonsmoking mothers by electronmicroscopy. In the smoking group these vessels were characterized' by subintirnal edema with- destruction of the intimal elastic membranes, a marked decrease in collagen content, and proliferation of myocytes. Asmussen postulated that similar damage may occur in the fetal and infant vascular system. To what extent such changes may predispose to the subsequent development of vascular disease remains unknown. The author, regarded most of the changes observed in smokers' vessels as degenerative, but _ mentioned the possibility that the thickening of the basement membrane observed in smokers might be an attempt at repair (4, 5). Naeye (97) has described an increased frequency of placental microscopic lesions associated with smoking. These include: cytotrophoblastic hyperplasia, obliterative endarteritis, stromal fibrosis, and small villous infarction. Smokers also demonstrated an increased frequency of necrosis and inftammation in the decidua capsularis and in " the decidua basalls at the placental margin. Placental features observed less frequently in smoker;s placentas were excessive syncytial knots and various thrombotic phenomena. Naeye found increasing placental enlargement with smoking level, accompanied by decreasing birth weight and a consequent increase in the placental ratio. The author stated that "as smoking increased, placentas developed microscopic lesions characteristic of underperfusion of the uterus.° Naeyels data showed positive trends with maternal smoking level for some findings and negative trends for others (97). Many of the changes cited were of low frequency in all groups, and nor ciear pattern of possible mechanisms of action emerged. Other studies that may shed light on these complex interreiationships include the report by 6oujard and colleagues that heavy alcohol consumption as well as smoking contributes to the risk of stillbirth caused by abruptio placentae. In a prospective survey of 9,169 women, the risk of stillbirth was 21 per 1,000 in smokers who were light or nondrinkers, 20 per 1,000 in nonsmoking drinkers of 45 ml or more of absolute alcohol per day, and 8.5 per thousand for nonsmokers who drank less than 45 ml per day. The small number of smokers who were also heavy drinkers had stillbirth rates of , 269 TIMN 0048486

50.5 per 1,000 (95 women with 5 stillbirths). The proportions of these deaths that were attributable to abruptio placentae increased with smoking and with drinking (122). i More research is needed to define possible pathways of .-actions by whieh the active components of cigarette smoke affect pregnancy complications that may lead, in turn, to fetal death in utero or to preterm birth with or without survival. EXPERIMENTAL STUDIES Tobacco Smoke Tobacco smoke contains more than 4,000 compounds including: carbon monoxide, oxides of nitrogen, ammonia, polycyclic aromatie hydrocarbons, hydrogen cyanide, vinyl chloride, and nicotine. For the pregnant woman and fetus the most impor- tant of these appoear to be nicotine, carbon monoxide, and the polycyclic aromatic hydrocarbons. Nicotine The effect of nicotine on sympathetic and parAsympathetic 'gangiia, skeletal muscles, and the central nervous system Is similar to that of acetylcholine. At all three sites it first stimulates, then depresses. Minute doses of nicotine stimulate the chemoreceptors of the carotid and aortic bodies, causing reflex hypertension. Nicotine also releases epinephrine from the adrenal medulla, thereby producing cardiovascular changes. Thus, it can produce widely differing effects depending upon the dosage and the particular site that Is most sensitive to stimulation. Nicotine rapidly crosses the placenta to affect the fetus (146). Relatively mature rhesus monkey fetuses respond to nicotine infusion with a_ rise in blood pressure, bradycardia, acidosis, hypercarbia, and hypoxia (145). Maternal nicotine administration in rats also has been shown to affect the fetal central nervous system and its response to electrical stimulation during the newborn period (61, 82). Quigley, et al. noted that in moderate to heavy smokers, after 34 weeks gestation, smoking two cigarettes in 10 minutes was associated with a 60 percent increase in maternal plasma norepinephrine and epinephrine and a 20 percent increase in serum cortisol concentrations (122). These 270 TIMN 0048487

a 1 . changes also were associated with an increase in maternal pulse and blood pressure. Lehtovirta and Forss measured changes in placental intervilious blood flow using the 133 xenon method (71). Immediately after smoking, interviilous flow decreased 22 percent. These data correlate with the studies of Resnik, et al. (1979) (126), showing nicotine- induced increases in catacholamines and decreased uterine biood flow in sheep, , and of Haberman, demonstrating decreased uteroplacental blood flow in women, using ther- mography (53). Sastry and his colleagues have carried out a series of studies on the effect of nicotine on the human placenta. Nicotine added to a calcium-containing medium caused a 33 percent increase in the rate of acetylcholine release from isolated placental villi '(135). The authors postulated that this effect could account for the decrease in placental amino acid transport (129, ' 158) produced by nicotine-mediated cholinergic blockade (109). Rowell and Sastry also demonstrated that nicotine caused a 41 percent decrease in uptake of alpha amino Isobutyric acid in an experimental placental system (130). Their studies indicate that under normal circumstances acetyichotine exhibits a muscarinic effect facilitating placental amino acid upiake. Nicotine blockade iA the facilitating effects of acetylcholine on amino acid uptake may result in fetal growth retardation (130). These data agree with the 1977 work of Crosby, et al. in humans (28). Nicotine injection In rats results In prolonged gestation with lower than normal newborn weights. A possible cause of this prolonged gestation Is nicotine-induced delay. in ovum implantation. Yoshinaga, et al. tested this hypothesis, administering 7.5 mg nicotine tartrate twice daily from the morning of proestrus until the day of• sacrifice on days 1 to 5 of pregnancy (166). The nicotine injected animals demonstrated a delay of about 12 hours in ovum cleavage from the two-to the four-cell stage, and each step t of development after the four-cell stage was thereby delayed. In addition, ovum entry into the uterus, blastocyst formation, shedding of the zona pellucida, and implantation were delayed. Nicotine injection also was associated with a"crowding" of implantation sites toward the tubal ends of the uterine horns. During the preimplantation period the serum con- centrations of progesterone, luteinizing hormone, and prolactin were lower, while the concentrations of estrogen and follicle stimulating hormone were higher than in control animals. 271 ' TIMN 0048488

These workers suggested that the delayed ovu.-n implantation followed. a delayed. increase In progesterone secretion required to prepare the uterus for the implanting blastocyst, and that the delayed progesterone secretion results in part from nicotine-induced disturbed hypothalamus-pituitary balance. Hamosh, et al. observed that, while administration of 100 mg kg-1 day-1 nicotine to pregnant rats from day 14 gestation onward failed to affect the mother or fetus, admi- nistration of mg.kg-1.day-1, (a dose "comparable" to that of a 20 cigarette-per-day smoker) resulted in a decrease In litter size and an increase in stillbirth rate. Although administration of 100 mg kg-1 day.1 nicotine failed to affect newborn birth weight by 12 days of age continued maternal nicotine administration resulted in a 9 percent decrease in body weight and a 40 percent decrease in weight oUthe sto- mach contents. These decreases presumably resulted from lower milk production by the nicotine-treated animals (56). Carbon Monoxide (CO ) Carboxyhemoglobin concentrations of 4 to 5 percent are asso- ciated with numerous physiologic alterations in adults (21). Cigarette smoking raises the carboxyhemoglobin concentration 4.to 5 percent per paek smoked per day. Aithougti CO dif- fuses across the placenta relatively slowly [the -haif time equals 1.5 to 2 hr (74)], fetal carboxyhemoglobin con- centrations reflect those of the mother, and• under steady state conditions are 10 to 15 • percent higher than maternal levels (76). Elevated carboxyhemoglobin concentrations in the fetus are associated with decreased fetal blood oxygen tensions. These decreased oxygen tensions are associated with a redistribution of fetal blood flow to the brain, heart, and adrenal glands (150). . Carboxyhemoglobin concentrations have been described under several conditions of pregnancy. Davies, et al. (34) compared carboxyhemoglobin concentrations and "available oxygen" (a function of 02 content In ml.dl blood-1) in women who stopped smoking for 48 hours during the last trimester of pregnancy, with women who did not stop smoking, and with nonsmoking women. In those women who stopped smoking, earboxyhemoglobin concentrations decreased. "Available oxygen" increased about 8 percent due both to an increase in functioning hemoglobin and a shift in the oxyhemoglobin saturation curve; this increase in "available oxygen" should 272 TIMN 0048489

contribute to improved fetal oxygenation. ., : . Exposure of rabbits (6) and rats (43) to CO during gestation resulted in decreased fetal weights and increased- perinatal mortality. Such CO-exposed newborn animals showed less activity as well as decreased lung weights and decreased concentrations of brain protein, DNA, and the neurotransmitters norepinephrine and serotonin (49). Cellular hypoxia is the final common pathway mediating the adverse effect of CO on the developing fetus. Recent experimental studies have explored various aspects of CO-induced biochemical changes in the fetus and the newborn. Newby, et al. demonstrated a persistent effect of CO exposure in 8- and 13-day-old rats following a single 5-hour exposure to 1,500 parts per million (0.15 percent CO) (104). In these animals alpha methyl-p-tyrosine, a potent inhibitor of the enzyme tyrosine hydroxylase, was injected 1 hour before the CO exposure, and the extent of catecholamine depletion was taken as an index of the rate of catecholamine turnover. CO-treated rats showed increased steady state dopamine concentrations with decreased rates of dopamine turnover. In addition, the CO effect on dopamine turnover persisted for at least 3 to 6 weeks after a single exposure There was no CO effect on norephi- -old rats of 8-da . y < e nephrine concentrations or turnover rates, and the effect was not produced in rats exposed to 8 percent oxygen instead of carbon monoxide. This is consistent with the data of Coyle : and Campoehiaro, which indicates that a maturational event ; occurs in the striatum of the 8-day-old rat (27). Whether .: this event represents the age of functional maturity, initiation ; of dopaminergic transmission, or maturation of choiinergic ~ interneurons is unclear. Prenatal CO exposure may have long-term consequences : on central nervous system function. For instance, Dyer, et ; al. exposed female Long-Evans hooded rats to 150 ppm CO :_ throughout pregnancy (40). At birth the litters and mothers were placed in room air without CO. On day 65 electrodes ; were placed in the young rats' skulls, and 2 weeks later visually evoked potentials were recorded. Figure 12 > illustrates the effect of such prenatal exposure on the peak- to-peak amplitudes of the P1-N1 (fRst positive to first ' negative) component of the visual evoked potential from the ; cortex. Females showed a significant increase in P1-N1 ; amplitude at each of four flash intensities. Although the exact nature of this amplitude increase could not be determined, it suggests altered cell populations at the retinal, 273 4 490

FIGURE1zEffectof prenatal CO upon peak-to-peak amplitudes of the positive 1-negative 9 component of the flash evoked potential recorded from the RAT visual cortex. Vertical bars represent *SEM. 120 ,100~ 2W EFFECTS OF PRENATAL CO UPON ADULT PI-NI AMPLITUDES OF THE VISUAL EVOKED POTENTIAL 0-+ COt na8 0--+ C0 d n =15 o-o CONT 2 n=9 oM-o CONTT d nz9 ~ Z 4 la INTENSITY ( CANDl,EPOWER / 9.4 x 104 ) SOURCE: Dyer et al (40) 274 TIMN 0048491

, . geniculate, and cortical levels, and may represent impaired Inhibitory mechanisms, rendering other neurons more excitable. The question of the possible teratogenicity of CO has never been resolved. Schwetz, et al. exposed mice to 250 •, ppm CO for 7 or 24 hours per day, from days 6 through 15 -. 'of gestation, and rabbits to the same concentration from days 6 through 18 (141).' Blood carboxyhemoglobin concentration ranged from 10 to 15 percent. The fetuses of mice exposed to CO for 7 and 24 hours per day were slightly heavier and lighter, respectively, than those of the control animals. The only Increase In teratogenic effects were minor skeletal variants such as extra lumbar ribs and spurs. Polycyciic Aromatic Hydrocarbons The polycyclic * aromatic hydrocarbons (PAH) such as benzo(a)pyrene, are widely distributed mutagens and car- cinogens. These substances produced by incomplete combustion of organic material are important constituents of tobacco smoke. Exposure of cells to PAH induces the enzyme, aryl hydrocarbon hydroxylase. The inducibility of this enzyme system has been used by some workers to demonstrate, indirectly, that benzo(a)pyrene and other polycyclic hydro- carbons reach the placenta and fetus. The placental concentration of benzo(a)pyrene is highly correlated with the amount which a pregnant woman smokes (101, 115). In pregnant rats exposed to this substance higher doses were required to induce enzyme aciivity in the fetus as compared with the dose required to stimulate placental enzyme activity (157), suggesting that the placenta may protect the fetus from these substances. However, the placenta is not impermeable to benzo(a)pyrene (138). The placenta is involved in complex hormonal interrelations between mother and fetus, and oxidative enzyme pathways in the placenta arc important in maintaining hormonal and nutrient balance for normal fetal development. The hydroxylation of polycyclic hydrocarbons and the active'transport of various compounds by trophoblast cells may share common enzyme systems. Thus, the induction of various enzymes by polycyclic hydrocarbons may Interfere with normal transport systems. Another unanswered question concerns the carcinogenic risk for progeny exposed in utero to polycyclic aromatic hydrocarbons. The offspring of mice which were injected with benzo(a)pyrene late in gestation showed an increased incidence 275 OO4g492

of neoplasms of the lungs, liver, and mammary glands (105). Pelkonen, et al. determined that placental aryl hydrocarbon of smokers compared with nonsmokers (152). hydroxylase activity correlated closely with both the amount the mother smoked and qewborn weight (116). These authors suggested that the placental concentration of this enzyme may be used is a measure of fetal exposure to maternal cigarette smoking. Vaught, et al. also reported much higher aryl hydrocarbon hydroxylase activity in the placental microsomes Although currently available data do not allow a quan-• titative assessment of the genetic risk to man from cigarette smoking, such risk may occur since so many components of cigarette smoke are mutagens (as well as carcinogens) (11). Male cigarette - smokers may have an increased, number of ;m abnormal spermatozoa (154). Paternal and maternal ; chromosomal abberrations (107) and sister chromatid exchanges may be Increased in smokers (67). Because the proportion of smokers in the population is so high (between 30 and 50 percent), even a relatively weak mutagenic effect could have a significant effect on . the gene pool (11). Other Components Cyanide, another constituent of cigarette smoke, may contri- bute to retarded infant growth and increased perinatal mor- taiity. Smokers have increased levels of , cyanide and thiocyanate in body fluids. Serum centrations of vitamin 812, used in cyanide metabolism are decreased as well. Several workers have recorded increased thiocyanate concentrations In both women who smoke, and their fetuses (2, 144, 158). Pettigrew, et al. compared cyanide and thiocyanate concentrations in smokers and nonsmokers, matched for age, height, parity, and socioeconomic status (120). Cyanide and thiocyanate concentrations were two to four times greater in the blood and urine of smokers and in the urine of smokers' infants as compared with controls. Meberg, et al. reported that thiocyanate concentrations were correlated with cigarette consumption and inversety correlated with birth weight (85). Cadmium, another constituent of tobacco smoke, is concentrated in the placenta of smokers (.128). Webster exposed pregnant mice to 10 to 40 ppm cadmium and noted an inverse correlation between cadmium concentration and fetal weight (156). Lauwerys, et al. examined the effects of epidemiology 276

I ~ t ~ r .. ; . factors on heavy metal and CO concentrations in the blood, placenta, and fetus of smoking women .(70). Cadmium con- , centrations in* maternal blood were twofold greater than con- centrations In fetal blood, sugesting that the placenta acts as a barrier to this metal. They reported a correlation between maternal cadmium and carboxyhemglobin concentrations (14, 70). They also found that the cadmium concentration of smokers' placentas was about 25 percent greater than in a control group and that the placental cadmium concentration exceeded that of maternal blood about tenfold (128). FERTILITY ~ . - _.... •--.-.- • ~ Fertility results from the successful completion of a complex '~ type step-wise process beginning with gametogenesis, (sperm ~ ~ and egg production) continuing through gamete release • (ejaculation and ovulation), gamete interaction (fertilization), ; conceptus transport through the fallopian tube into the uterus, . and ending with implantation of the " bryo into the ' endometrial wall. An adverse effect of smoking on any of these steps may impair fertility. , . • ' Smoking and Reproduction in Women ; Several epidemiologic studies have suggested that smoking The decreases fertilit in women (147 119 55) 153 r , . y , , ; retrospective study of Tokuhata demonstrated that 21 percent ` of women who regularly smoked cigarettes were infertile while only 14 percent of those who never used tobacco regularly ? were (147). After several characteristics (cause of death, age at and year of death, education, occupation and frequency. : of marriage as well as husbands' smoking habits, education ~ and occupation) "were controlled, an excess of infertility was ' found in women who smoked. ': In a study on the return of fertility after discontinuing s contraception, Vessey, et • al. found a suggested reduction in ; fertility among women smoking 15 or more cigarettes per day ~ (153). Pettersson, et al. found a tendency toward a greater ' prevalence of secondary amenorrhea among smokers (4.8J100 ~ women) than among nonsmokers (3.71100 women) (119). ~ Hammond found that 49 percent of the nonsmoking women ~ ; between 40 and 49 years had regular menses while only 40 : percent of those smoking more than one pack a day had a f .l . 277 TIMN 0048494

regular menses (55). Conversely only 18 percent of nonsmokers had irregular menses while - 24 percent of those smoking -one or more packs of cigarettes per day said they. had irregular menses. Smoking women were also more likely to have an unusual~ vaginal discharge and vaginal bleeding than nonsmokers. Experimental studies have demonstrated alterations In luteinizing hormone release and a decreased ovulatory response In rats exposed to tobacco smoke (80). The effect of smoking on ovulation may result from direct effects of nicotine on the hypothalmus or pituitary. This would alter the release of gonadotropin releasing hor- mones from the hypothalamus or impair the pituitary response to releasing hormones. Smoking and Age of Menopause Substantial data demonstrate that smoking lowers the age of spontaneous menopause (63, 29, 7, 8, 72, 73). The recent study by Jick, et al. revealed a dose dependent decrease in the age of menopause in smoking women who live in Sweden and the United States (63). The median age of menopause in nonsmokers was 50; among those smoking one-half pack it was 49; in those smoking 1 or mote pack/day, it was 48. Similar studies have been published indicating an earier onset of menopause in smoking women in the United States (29), in England (7), in Germany (8), and in Sweden (72, 73). The mechanism of early menopause in smokers may be related to ovotoxins in cigarette smoke (41) or -to toxic alterations in the hormonal regulatory •mechanisms controlling the hypothalmic-pituatary-ovarian axis (80). One group of ovotoxins may be polycyclic aromatic hydrocarbons which have been. demonstrated to be metabolized by ovarian enzymes to toxic products which destroy oocytes in rat and mouse ovaries (83, 52). Evidence collected by Daniell (31) and Lindquist (72) suggestt that the earlier menopause of smokers is not related to weight differences between smokers and nonsmokers but is a direct result of some component of cigarette smoke. Smoking and Reproduction in Men Spermatogenesis, sperm morphology, sperm motility (18, 137, 154, 69) and androgen secretion (12, 117) appear to be 278 . TIMN 0048495

. . altered in men who smoke. Viczian (154) has demonstrated decreased sperm density, a cigarette-dose-dependent decrease in sperm motility, and • a cigarette-dose-dependent increased abnormal sperm morphology among smokers. In metabolic studies of alcoholic men admitted to a clinical research center, an inverse relationship between number of cigarettes smoked and reduction of testosterone levels was seen (117). Briggs (12), has reported lower plasma testosterone among smoking men compared to matched nonsmoking controls and has shown that cessation of smoking resulted in increased testosterone levels in these men. Wintermitz and Quillen (163) in a study on the acute effects of smoking in men demonstrated increases in plasma cortisol and growth hormone during the smoking period. Growth hor- mone returned to the presmoking level shortly after the smoking period, and cortisol fell gradually to the presmoking level by 90 minutes after cessation of smoking. Urinary catecholamines were higher on the smoking day than the nonsmoking day. No acute changes were observed In gona- dotropins or testosterone in these men. Studies in experimental animals have also shown that tobacco smoke impairs spermatogenesis (41, 155). Smoking also lowers sexual activity in male rats (19). These data suggest two possible mechanisms of action of smoking on male reproduction. A, component of cigarette smoke may have a direct action on the -testes, disrupting gamete production. This would be consistent with the suggested effect of cigarette smoke on the ovary. In addi- tion, cigarette smoke Is known to contain compounds which are mutagenic (64). Alternatively, cigarette smoke may interfere with the regulatory mechanisms controlling the hypothalamic- pituitary-testicular axis. Fertilization and Conceptus Transport The effect of- smoking on sperm-egg interaction (fertilization) has not been studied in mammalian species. Evidence from mammalian species demonstrates that nicotine promotes polyspermy (the entrance of more than one sperm into the oocyte) (77). Polyspermy would result in abnormal embryonic development and early abortion, which is one known effect of smoking (65). The effect of smoking on conceptus transport • in the fallopian tube or entry into the uterus is unknown; however, r 279 TiMN 0048496

some evidence suggests that smoking can alter the amplitude and tone of contractions measured during the rubin uterotubal insuffiation test (a combined measure of uterotubal junction and tubal patency) (102). In summary, cigarette smoking appears to exert an adverse effect on fertility. Further studies are needed to quantify the effects, identify etiologic agent(s), and define the mechanism(s) of action. 280 TIMN 0048497

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(132) RUSH, D., KASS, E.H. Maternal smoking: A reassessment of the association with perinatal mortality. American journal of Epidemiology 96 (3): 183-196, September 1972. (133) RUSSELL, C.S., TAY1.OR, R., LAW, C.E. Smoking in pregnancy, maternal blood pressure, pregnancy outcome, baby weight and growth, and other related factors. A prospective study. British journal of Preventive and Social Medicine 22(30): 119-126, July 1968. (134) RUSSELL, C.S., TAYLOR, R., MADDISON, R.N. Some effects of smoking in pregnancy. journal of Obstetrics and Gynaecology of the British Common- wealth 73: 742-746, October 1966. (135) SASTRY, B.V.R., OLUBADEWO, J.O., BOEHM, F.H. Effects of nicotine and cocaine on the release of acetyi-choline from isolated human placental , villi. Arch. int. Pharmacodyn. Therap. 229: 23-36, 1977. (136) SAXTON, D.W. The behavior of infants whose mothers smoke in pregnancy. Early Human Development 2/4: .363-369, 1978. (137) SCHIRREN, C., GEY, G. Der Einflusz des Ranchens auf de Fortpflanzungs-fahigkeit beir Mann und Fran. - Zettschrift Hant-Geschl. Krkh. 44: 175- 182, 1966. (138) SCHLEDE, E., MERKER, H.J. Effect of benzo(a)-, pyrene treatment on the benzo(a)pyrene hydroxylase activity in maternal liver, placenta, and fetus of the rat during day 13 to day 18 of gestation. Naunyn-Schmiedeberg's Archives of Pharmacology 272(1): 89-100, December 21, 1972. (139) SCHORAH, C.J., ZEMROCH, P.J., SHEPPARD, S., SMITHELLS-, R.W. Leucocyte ascorbic acid and pregnancy. British journal of Nutrition 39: 139-149, 1978. (140) SCHWARTZ, D., GOUJARD, J., KAMINSKI, M., RUMEAU- ROUQUETTE, C. Smoking and pregnancy: Results of a prospective study of 6,989 women. Revue Europeene d'Etudes Cliniques et Biologiques 17 (9): 867-879, 1972. (141) SCHWETZ, B.A., SMITH, F.A., LEONG, B.K.J., STAPLES, R.E. Teratogenic potential of inhaled carbon monoxide in mice and rabbits. Teratology 19: 385-392, 1979. 293 t TIMN 0048510 -

(142) SIMPSON, W.j. ' A preliminary report on cigarette smoking and the incidence of prematurity. American journal of Obstetrics and Gynecology 73 (4): 808-815, April 1957. (143) STEELE, R., LANGWORTH, J.T. The relationship of antenatal and postnatal factors to sudden unex- pected death in infancy. Canadian Medical Assoc- iation Journal 94: 1165- 1171, May 28, 1966. (144) STOA, K.F. Studies on thiocyanate in serum. In: Second Medical Yearbook, Bergen, Norway, University of Bergen, 1957, pp. 14. (145) SUZUKI, K., HORIGUCHI, T., COMAS-URRUTIA, A.C., MUELLER-HEURACH, E., MORISHIMA, H.O., ADAMSONS, K. Pharmacologic effects of nicotine upon the fetus ind mother in the rhesus monkey. American journal of Obstetrics and Gynecology 111 (8): 1092-110'1, December 15, 1971. (146) SUZUKI, K., HORIGUCHI, T., COMAS-URRUTIA, A.C., MUELLER-HEUE?ACH, E., MORISHIMA, H.O., ADAMSONS, K. Placental transfer and' distribution of nicotine in the pregnant rhesus monkey. American Journal of Obstetrics and Gynecology 119(2): 253-262, M ay 15, .1974. (147) TOKUHATA, G. Smoking in relation to infertility and fetal loss. Archives of Environmental Health 17:. 353-359, 1968. ' (148) UNDERWOOD, P., HESTER, L.L., LAFFITTE, T., JR., GREGG, K.V. The relationship of smoking to the outcome of' pregnancy. American Journal of Obstetrics and Gynecology 91(2): 270-276, January 15, 1965. (149) UNDERWOOD; P.B., KESLER, K.F., . OtLANE, J.M., CALLAGAN, D.A. Parental smoking empirically related to pregnancy outcome. . Obstetrics and Gynecology 24(1): ' January 1-R, 1957. (150) U.S. DHEW. Smoking and Health: A Report of the Surgeon General, 1979. DHEW Publication Nn. ((PHS) 79-50066). (151) U.S. PUBLIC HEALTH SERVICE. The Health Conse- quences of Smoking. A Report of the Surgeon General. U.S. Department of Health, Education, and Welfare, DHEW Publication No. (HSM) 73-A704, 1973, pp. 99-149. 294 i 4 511

4 ~ O • . : (152).VAUGHT, J.B., GURTOO, H.L., PARKER, N.B., LEBOEUF, R., s .ti DOCTOR, G. Effects of smoking on benzo(a)pyrene metabolism by human placental microsomes. Cancer (153) VESSEY, M.P., WRIGHT, N.H., MCPHERSON, K., WIGGINS, P. ~ Fertility after stopping different methods of . contraception. British Medical Journal 1(6108): : 265-267, 1978. (154) VICZIAN, M. Results of spermatozoa studies In cigarette smokers. Z. Haut Geschlechtshl. 44(5),, , : 183 -187, 1969. (155) VICZIAN, M. The effect of cigarette smoke Inhalation on spermatogenesis In rats. Experienta 24: 511-513, 1968. (156) WEBSTER, W.S. Cadmium-induced fetal growth retar- dation in the mouse. Archives of Environmental Health 33 (1): 36-42, January/February 1978. English. (157) WELCH, R.M., GOMMI, B., ALVARES, A.P., CONNEY, A.H.. Effect of enzyme induction on the metabolism of berizo(a)pyrene and 3-methyl-4- monomethylaminoazobenzene in the pregnant and fetal rat. Cancer Research 32(5):' 973-978, May 1972. (158) WENNERBERG, P.A., WELSCH, F. Effects of cholinergic drugs on uptake of 14 C-aminoisobutyric acid by human term placenta fragments: Implication for ace- tyicholine recognition sites and observations on the binding -of radioactive cholinergic ligands. Fed. Proc.,36: 980, 1977. (159) WILSON, E.W. The effect of smoking in pregnancy on the - placental co-efficient. New Zealand Medical Journal 74(475 ): 384-385, 1972. (160) WILSON,• J., MATTHEWS, D.M. Metabolic inter- relationships between cyan ide, thiocyanate and vita- ' min B12 in smokers and nonsmokers. Clin. Sci. 31: 1-7, 1966. (161) WINGERD, J., CHRISTIANSON, R., LOVITT, W.V., SCHODEN, E.J. Placental ratio in white and black women: Relation to smoking and anemia. American Journal of Obstetrics and Gynecology 124(7): 671-675, April 1, 1976. 295 TIMN 0048512

(162) WINGERD, J., SCHOEN, E.J. Factors influencing length at birth and height at five years. Pedia- trics 3(5): 737-741, May 1974. (163) WINTERNITZ, W.W., QUILLEN, D. Acute hormonal response to cigarette. Journal . Clinical Pharma- cology: 389-397, 1977. (164) YERUSHALMY, J. Mother's cigarette smoking and survival of Infant. American Journal of Obstetrics and Gynecology 88(4): 505- 518, February 15, 1964. (165) YERUSHALMY, J. The relationship of- parents' cigarette smoking, to outcome off pregnancy-- Implications as to the problem of inferring causation from observed associations. American Journal of Epidemioiogy 93(6): 443-456, June 1971. (166) YOSHINAGA, K., RICE, C., KRENN, J., PILOT, R.L. Effects of nicotine on early pregnancy in the rat. B io i. Reprod. 20: 294-303,. 1979. (167) ZABRISKIE, J.R. Effect of cigarette smoking during pregnancy. Study of 2000 cases. Obstetrics and Gynecology 21(4): 405-411, April 1963. 296 -'TIlliIN 0048513

; : , ti. : : r r$: PEPTIC ULCER DISEASE There is little Information dealing 'specifically with the relationship between smoking and peptic ulcer disease in women. The data which are available suggest the same trend toward higher prevalence of peptic ulcer disease among women who -smoke as is observed among men who smoke. Table 1, extracted from the 1979 Surgeon General's Report, shows that the prevalence of "peptic ulcer" in female smokers was higher in two out of three studies of *women, which showed a twofold or 1.6 fold higher prevalence (10). The one study which failed to demonstrate an increased prevalence was conducted in rural Poland where very few women smoke (only 7 percent) (9). The median ratio of smoking ulcer patients to nonsmoking ulcer patients has been reported to be 1.7 for men (10). Thus, women • smokers seem to show greater susceptability to ulcer disease than do nonsmokers. The population of women with ulcers contains a*greater proportion of smokers than does the group of women without ulcers. Alp, et al. performed a retrospective analysis of 638 patients with gastric ulcer, 230 of whom were women (2). There were 1.9 times as many smokers In the group of women ulcer patients as in an age-matched control group. However, even among the ulcer patients, only 39 percent were smokers. In a smaller series of 31 female patients admitted to hospi-.. tals with hemorrhage from or perforatiori of gastric or duodenal ulcers, the prevalence of smoking was 26 percent in both ulcer patients (8/31) and controls (8/31) (1). In a report examining the effect •of smoking on healing rates of gastric and duodenal ulcers, Doll, et al. studied 92 women with gastric ulcer and 54 women with duodenal ulcer (4). Smoking was 1.6 times more common in women gastric ulcer patients as in controls matched for age and place of residence (p < 0.01). There was no significant excess in the proportion of smokers in the group with duodenal ulcer. The effect of smoking on healing .rate was reported for men and women grouped together, so no conclusion regarding specific effects on women is possible. Although some studies of etiological factors in smoking-induced ulcer disease (gastric acid secretion, pancreatic secretion, etc.) have included women, the number of women has been small, or the data from women have not been presented separately. In summary, the evidence currently available documents an inereased prevalence of peptic ulcer disease in women who 297 TIMN 0048514

TARLE 1.-Prevalence of Peptic Ulcer In Smoking and Non-Smokin6 Women (Number per 100). REFERENCF NO. WITH ULCERS SMciKERS Mc)IVSKIKERS RATIO (Prevalence among Smokers) Higgins, M.W. 47 ?.R 1.4 (Prevalence among Nonsmokers) 2.0 (1966) (7) Friedman, G.D. 1092 6.3 3.9 1.6 (1974) (5) Jedrychowskl, W. 26 0.8 1.3- 0.6 (1974) (9) !

smoke. No data are available concerning specific effects of smoking in women on gastric acid secretion, gastric emptying, pancreatic secretion, or other processes which might be involved in the pathogenesis of peptic ulcer disease. SUMMARY The 1979 Surgeon General's Report included evidence that cigarette smoking In males was significantly associated with the incidence of peptic ulcer disease and increased the risk of dying from peptic ulcer disease by approximately two-fold. The effect of smoking on pancreatic secretion and pyloric reflux demonstrated among men may provide a mechanism by which peptic ulcers develop. 1. Female smokers show a prevalence of peptic ulcer- higher than that of nonsmokers by approximately two-fold. 2. The effect of cessation on healing is not known. r* 299

.PEPTIC ULCER: REFERENCES , I (1) ALLIR(1NE, A., FLINT, F.J. Bronchitis, aspirin, smoking and other factors * in the aetioiogy of peptic ulcer. Lancet 2: 179-1R?, July 26, 11092 . (2) ALP, M.H., HISLOP, I.G., GRANT, A.K.. c:astric ulcer in south Australia 1954-1Q63. 1. Epidemiological factors. Medical journal of Australia 2: 11?8-1132, December 12, 1970. (3) BRANDSRnRG, 0., CHRISTENSEN, N.j., GALRO, H., RRANDSBORG, M:, LOVGREEN, N.A. The effect of exercise, smoking and propranolol on serum gastrin in patients with duodenal ulcer and vagotimized subjects. Scandinavian journal of Clinical and Laboratory Investigation SR(5):, 441-446, May 1978. (4) DOLL, R., IONES, F.A., PYC;QTT, F. Effect of smoking on the production and maintenance of gastric and duodenal uicers. Lancet 1: 657-. 662, March 29, 1958. (5) FRIEDMAN, G.D., SIEGELAUR, A.R., SF.LTZER, C.C. Cigarettes, alcohol, coffee and peptic ulcer. New England journal of Medicine 290(9): 469- 473, February ?R, 1974. _ (6) GRIMES, D.S., GODDARD, J. Effect of cigarette smoking ori' gastric emptying. Rritish Medical Journal 2: 460-461, August 12, 1078. (7) HIGGINS, M.W., KJELSBERG, M. Characteristics of smokers in Tecumseh, Michigan. 11. The distribution - of selected physical measurements and physiological variables and the prevalence of certain diseases in smokers and nonsmokers. American journal of Epidemiology 86: 6f1-77, 1967. (8) IVEY, K.J., TRIGGS, E.. Absorption• of nicotine by the human stomach and its effects on gastric ton fluxes and potential differences. American journal of nigestive r)iseases 23(9): R09-814, September 1978. (9) JEDRYCHnWSKI, W., POPIELA, T. Association be- tween the occurrence of peptic ulcers and tohaeco smoking. Public Health, London RR(4): 195-2m, 1974. 300 ~ TIMN 0048517

(10) U.S. PUBLIC HEALTH SERVICE. Smoking and Health. A Report of the Surgeon General. U.S. Department of Health, Education, and. Weifare, Office of the Assistant Secretary for Health, Public Health Service, Office on Smoking and Heatth.- DHEW Publication No. (PHS) 79-50066, 1979. 301 TIMN 0048518

INTERACTIONS OF SMOKING VyITH DRUGS, FOOD CONSTITUENTS AND RESPONSES TO DIAGNOSTIC TESTS Since most published studies investigating the effect of cigarette smoking on measures of health were performed in mixed populations, it Is difficult to demonstrate specific factors applicable only to women. Neither the differences between men and women regarding the metabolism and action of drugs nor the pharmacological basis for differences between smokers and nonsmokers is well understood. The same is also true of the observed variations in laboratory values and nutritional needs. Thus, the associations for women between smoking, drugs, variations in clinical laboratory values, and nutritional needs require further study. Women Smokers and Nonsmokers and Drug Consumption Patterns The drug consumption pattern of women as compared to men has been studied by a number of investigators using different methodologies. The results consistently show that women are prescribed and take more" prescription drugs than men (7,20). In one study where 1-year drug histories were used, the per- centage of women using prescription drugs was 29 percent as compared to 13 percent for men (20). Another study which examined only drugs consumed within '48 hours of the inter- view showed that 60.2 percent of the *women had taken medication compared to 41.8 percent of the men (7). The two . studies cited are unique in the realm of drug usage studies because they measure 'actual self-administration of. drugs rather than counting physician prescriptions or pharmacy dispensing patterns. Unfortunately, neither of these studies quantified information according to whether the subjects were smokers or nonsmokers. Other reports show that smokers tend to use more drugs, especially of the psychotherapeutic type and drink more coffee and alcoholic beverages than nonsmokers (21,30). In only one study have women smokers and nonsmokers been compared for use of all drug categories; these data were derived from a self-administered questionnaire asking about drug use for the past year (25). As Table 1 shows, women smokers take more of almost every type of drug" than nonsmokers. When the data were organized according to age 302 ' TIMN 0048519

TABLE 1.-Ratio of Percent Usage of Drug Ciasses, Women Smoker/Nonsmoker Status* WMITE BLACK ASIAN a Antihistamine or alter~y medicine 0.8 0.9 0.6 Cough medicine 1.7 1.8 0.7 Asthma medicins 0.9 1.0 0.9 , Aspirin-containing drugs 1.2 1.2 0.9 Pain medicine 1.2 1.2' 1.0 Codeine, morphins, Darvon, Percodan, Demeroi 1.5 1.6 1.2 Phenobarbitai or other barbiturates 1.3 1.8 1.6 Sleeping Pills 1.2 1.3 1.3 Tranquilizers 1.5 1.6 1.8 Anticoasutants 1.3 0.8 0.0 Digitalis or other heart medication 1.0 0.8 0.1 Antihypertensives 0.8 1.1 0.9 Diuretics 1.1 1.0 1.3 Cortisone-type medication 1.0 1.2 1.0 Hormones 1.2 1.3 1.4 Insulin or diabetic pills 0.9 0.8 ' 0.9 iron or anemia medications 0.9 0.9 0.9 Thyroid medication 1.1 1.3 2.3 , Pills to control periods 1.3 1.2 1.5 .~ Contraceptives 1.2 1.1 1.3 ; Senzedrine or Dexsdrins 1.6 1.1 1.1 ~ Weight reduction medication 1.1 0.9 1.3 : Penicillin or other antibiotics 1.2 1.2 1.0 f Sulfa drugs 1.1 1.2 0.8 ., Stomach or ditestion medicine 1.2 1.2 1.3 : = SOURCE: •Adapted from Seltzer (25). Y r 303 TIMN 0048520

groups, the 15-to-19-year-oid group of women showed a marked eievation In drug use among smokers (Table 2). Although the data are preliminary, a trend that female 'smokers consume drugs with greater frequency than female nonsmokers is suggested. It is beyond the scope of this chapter to differentiate between the behavioral components of this phenomenon or to address the argument that women who smoke are less healthy than nonsmokers. It is beneficial, however, to examine the few reports that address the differences in drug action between smokers and nonsmokers, regardless of the reasons for drug use. ; s Altered Clinical Response to Drug Therapy by Smokers Compared to Nonsmokers The number of studies investigating the differences in the clinical responses to a drug by smokers and nonsmokers are far fewer in number than the studies examining the alterations in metabolism and biochemistry of drugs in smokers. The 1979 Surgeon Generalos Report included an extensive review of the alterations in drug disposition that occur in smokers (29). That information Is useful for clarifying mechanisms by which smoking alters drug metabolism, absorption, excretion, and other functions. The clinical significance of these alterations has not been clarified, however. The most exhaustive examination of alterations in srnokers' clinical . response to drugs was done by Jick and his associates in the Boston Collaborative T)rug Surveillance Program (RCDSP). Over the past several years, this group has investigated the clinical response of smokers and nonsmokers to six different drugs: propoxyphene (Darvon) (3); diazepam (Valium) (4); chlordiazepoxide (Librium) (4); phenobarbital (4); chlorpromazine (Thorazine) (28); and theophyiiine tea - (22). The differences observed between smokers and nonsmokers • were consistent among men and women, except for the theophylline study, in which the toxic effects of therapy were slightly more freouent among women (13.4 percent) than among men (9.19 percent). Only in the chlorpromazine (28) study did the studv group (those taking chlorpromazine) contain more women than men, an observation that supports other reports that women use major tranauilizing agents more frequently than men (21). Since the published RCDSP data is not organized according to groups of women smokers and nonsmokers, any 304 TIMN 0048521

> ; i TABLE 2.-Percentage of Positive Responses Among Females In Age Group 15-19° QUESTiON ShlOKERS NONSA00KERS Taken phenobarbitai or barbiturates? 2.3 1.0 Taken codeine, morphine, etc.? 16.0 6.5 Taken Benzedrine or Dexedrine? 4.9 0.3 Taken penicillin or other antibiotics? 33.0 25.8 Taken pills to prevent pregnancy? 27.0 9.7 SOURCE: *Adapted from Seitzer (25) 305 E TIMN 0048522

difference In drug use between these groups is not reflected in the data analysis. However, it is important to note that these studies, except as , noted In the chlorpromazine study, predominantly involved men. It has been shown that women report more frequent use of the minor tranquilizers such as diazepam and 'chlordiazepoxide (2A). Thus these studies shouidnot, be interpreted as reflecting drug response among the general population (20). The studies on chiorpromazine, diazepam, and chiordiazepoxide showed a lessened frequency of the adverse effect. of drowsiness among smokers as compared to nonsmokers (4,2R). Conversely, no difference was reported for phenobarbital (4). The analgesic effect of propoxyphene was reduced In smokers, an effect which was not observed in smokers on aspirin, codeine, acetaminophen, or combinations of these drugs (3) . .'The evidence for increased theophylline' metabolism in smokers is well established and predicts the observed clinical response to theophylline (14). The RCDSP study of theophylline showed that smokers not, only required larger doses of theophyiline for efficacy, but also- were less likely to report adverse effects than nonsmokers, even though they, recuired larger doses. - Theoretically, then, because of a decreased clinical response to a. drug, the tendency would be for the smoker to require increased doses to achieve the same therapeutic effect as a nonsmoker. " Therapeutic r-•:efficacy and adverse side effects in relationship to gender, smoking history, and drug consumption patterns have not been adeauately studied, although the preliminary evidence would indicate an area of potential toxic drug effects and/or therapeutic failures. Oral Contraceptives and Smoking Chronic estrogen therapy has a profound interaction with chronic tobacco use. ' Again, the RCDSP has been most instrumental in assessing the influence of these two factors on the health status of women. In assessing the relative risk of stroke in women who smoke and take oral contraceptives, the data from the Collaborative Group for the Study of Stroke in Young Women show that smoking alone increased the risk of hemorrhagic stroke (i.e., subarachnoid) from 1.0 for a nonsmoker who did 306 , TIMN 0048523

. not use oral contraceptives, to 2.6 for a smoker who did not use oral contraceptives. A smoker taking oral contraceptives had a relative risk of 6.1 or 7.6 (depending on the control group) (5). Similar increases in risks do not seem to occur for thrombotic stroke in the smoker taking oral contraceptives, but the risk of a thrombotic stroke for a women using oral contraceptives, alone, is about nine times greater than that for a noncontraceptive user (6). Again using the BCDSP data, the risk of nonfatal myocardial infarction among women under 38 is very low among nonsmokers whether or not they use oral contraceptives. However,. the risk to women who both smoke and use oral contraceptives Is substantially higher, ranging from an estimated one per 8,400 annually In women aged 27 to 37 -° - years to one per 250 for women aged 44 to 45 years (17). ; ilar study of noncontraceptive estrogens, similar risks In a sim were demonstrated for women who both smoke and , use estrogens (16). These findings are in agreement with studies done In Great Britain where oral contraceptives were associated with an overall increase in cardiovascular disease iny ouung women (23). Another group which has investigated the link between smoking, oral contraception, and myocardiai infarction reported,,,: that there Is a considerable interaction between smoking and contraceptive use. The group found that rate of acute myocardial infarction among female smokers on oral contraceptives is greater than could be accounted for by either smoking or contraceptives alone (26). In earlier studies this same group concluded that there was a dose- response relationship between smoking and myocardial infarction in , women, and that among women smoking 35 or more cigarettes per day, the rate of myocardial infarction was estimated to be 20 times higher than among those who never smoked (27). These data lend themselves to the prediction of risk in only a very general way and provide no particular measures by which a woman--smoker or nonsmoker--can evaluate her own risk of experiencing one of the adverse effects described. The following section reviews some of the laboratory values that are altered by smoking. Unfortunately, many of the largest studies on the correlation between smoking and alterations in clinical laboratory values have focused on men. 307 I TIMN 0048524

Alterations in Normal Clinical Laboratory Values in Women Smokers . Only a few investigators have studied clinical laboratory :values in women smokers and nonsmokers (1, 8, 9 , 1,1, 13, 15, 10, 31). Many of these studies show statistical ly significant differences in a variety of common parameters. The clinical significance of these differences may not be ipparent, however, since the actual differences between women smokers and nonsmokers are small. For example, a study of packed red cell volume (PCV) and hemoglobin (Hb) in women smokers and nonsmokers showed the PCV and Hb for nonsmokers to be 41.95 and 13.85 compared to 42.94 and 14.16 for smokers--a difference significant at P < 0.05, but a discrimination which physician or patient may find difficult to assess (15). Small differences in laboratory values between smokers and nonsmokers can be seen in a number of serum chemistry and hematologic tests. One measurement that shows a wide enough variation between smokers and nonsmokers to be recognized clinically is the leukocyte count of a smoker (11,13). It is important to recognize that a WBC of 12,000 per cu/mm is within the normal range for a heavy cigarette smoker, andt that the differential count remains normal (11). In one study, individuals with chronic bronchitis were excluded from evaluation of . leukocyte counts, and the same relative increase in leukocyte count was observed (13). In several studies of triglyceride and cholesterol values in smoking and nonsmoking women, an elevation of both values, which was not statistically significant, was seen in smokers. The addition of oral contraceptive use to smoking caused a significant elevation ove,r the nonsmoker,, noncontraceptive user. The nonsmoker values were 79 + 6.8 mg/100 ml for triglycerides and 157 + 7.5 mg/100 ml for cholesterol. In the smoker they were 110 + 14.8 mgj100 ml and 174.3 + 8.8 mg/100 ml respectively, whereas the smoker using oral contraceptives had. a triglyceride value of 150.0 + 14.1 mg(100 ml and , a cholesterol value of 186.1 + 8.4 mg/100 ml. In this same study, there was no significant difference between the level.s of vitamins A, E or C in smoking and nonsmoking women (31). A number of investigators have measured vitamin C levels in smoking and nonsmoking women, with extreme variation in results. Some showed decreased plasma and leukocyte vitamin C levels in smokers, and others showed no 308 , , a ' TIMN 0048525

, a differences between smokers and nonsmokers. The discre- pancies in these results may in part be related to the amount of dietary vitamin C habitually consumed by the subjects in the various studies (31). Changes in serum proteins were the subject of another study of women smokers and nonsmokers (30). Significant differences in all serum protein fractions were found in c igarette smokars compared to nonsmokers. !n general, the effects increased with the amount smoked. Past smokers showed globulin values that were significantly below those of women who never smoked, but there was no difference observed in the other serum protein fractions between past smokers and those who had never smoked. The Influence of Smoking on the Nutritional Needs of Women Outside of a possibly increased need for vitamin C in women who smoke, there is very little information about other nutrient requirements in smokers. In recent years a great deal of time has been spent studying the influence of smoking on fetal development, a subject covered elsewhere In this volume. The special, nutritional needs of the nonpregnant smoking woman have not been dealt with in any systematic way. A recent study involving obese women looked at the influence of smoking cessation on body weight (2). Although the data are innately biased because the study group consisted of women enrolled in a weight loss program, the results showed that women who smoked less than a half pack of cigarettes a day, gained 4 pounds after they quit. Heavy .smokers consuming over. two packs a day gained an average of 30 pounds over several decades. Moderate smokers gained an intermediate amount. This study does not contradict a commonly held notion that women gain weight when they stop smoking; however, it provides no behavioral or physiological hypothesis for this phenomenon. 309 I TIMN 0048526

Summary There „is _a, paucity of data on what short-term effects cigarette smoking has on drug response, drug interaction, and the nutritional requirements of women. Preliminary studies show altered responses to drugs and variations in laboratory measurements. Further study is needed. to, clarify the significance of these. observations for women who smoke. 7 310 ' TIMN 0048527

FOOD AND DRUG METABOLISM: REFERENCES (1) BILLIMORIA, - J.D., POZNER, H., METSELAAR, B., BEST, F.W., JAMES, D.C.D. Effect of ciga- rett8 smoking on lipids, lipoproteins, blood coagulation, fibrinolysis and cellular compo- nents of human blood. Atherosclerosis 21 (1): 61-76, January-February 1975. (2) BLITZER, P.H., RINdM, A.A., GIFFER, E.E. The effect of cessation of smoking on body weight in 57,032 women: Cross sectional and longi- tudinal analysis. journal of Chronic Diseases 30(7): 415-429, July 1977. (3) BOSTON COLLABORATIVE DRUG SURVEILLANCE PROGRAM. Decreased clinical efficacy of propoxyphene In cigarette sinokers. Clinical Pharmacology and Therapeutics 14(2): 259-263, March-April 1973. (4) BOSTON COLLABORATIVE DRUG SURVEILLANCE PROGRAM. Clinical depression of the central nervous system due to diazepam and chlordiazepoxide cigarette smoking and age. In relation to New England journal of Medicine 288(6): 277- 280, February 8, 1973. _ (5) COLLABORATIVE GROUP FOR THE STUDY OF STROKE IN .YOUNG WOMEN. Oral contraceptives and stroke in young women. journal of the American Medical Association 231(7): 718-722, February 17, 1975. (6) COLLABORATIVE GROUP FOR THE STUDY OF STROKE IN YOUNG WOMEN. Oral contraceptives and in- creased risk of cerebral ischemia or throm- bosis. New England Journal of Medicine 288(17): 871-878, 'April 26, 1973. (7) CRAIG, T.L., VANNATTA, P.A. Current medica- tion use and symptoms of depression in a gene- ral population. American Journal of Psychia- try 135(9): 1036-1039, September 1978. (8) DALES, L.G., FRIEDMAN, Q.D., SIEGELAUB, A.B., SELTZER, A.C. Cigarette smoking and serum chemistry tests. Journal of Chronic Diseases i 27(6): 293-307, August 1974. , , ' : 3 11 : ~ r T-IMN 0048528

(9) DALES, L.G., FRIEDMAN, Q.D., SEIGELAUB, A.B., SELTZER, A.C., URY, H.K. Cigarette smoking habits and urine characteristics. Nephron 20: 163-170, 1978. (10) DESMOND, P.V., ROBERTS, R.K., WILKINSON, Q.R., SCHENKER, S. No effect of smoking on meta- bolism of chlordiazepoxide. New England Journai of Medicine 300(4): 199-200 January 25, 1979. FRIEDMAN, Q.D., SIEGELAUB, A.B., SELTZER, C.C., FELDMAN, R., COLLEN, M.F. Smoking habits and the leukocyte count. Archives of Environ- mental Health 26(3): 137-143. March 1973. GLAUSER, S.C., GEAVSER, E.M., REIDENBERG, M.M., RUSY, B.F., TALLARIDA, R.J. Metabolic changes associated with the cessation of . cigarette smoking. Archives of Environmental Health 20(3): 377-381, March 1970. (13) HELMAN, N.., RUBENSTEIN, L.S. The effects of age, sex, and smoking on erythrocytes and leukocytes. American Journal of Clinical Pathology 63: 35-44, 1975. (14) HUNT, S.N., JUSKO, W.J., YURCHAK, A.M. Effect of smoking on theophylline disposition. Ciinicai Pharmacology and Therapeutics (Part 1) .19(5): 546-551, May 1976. _ (15) ISAGER, H., HAGERUP, L. Relationship between cigarette smoking and high packed ceil volume and haemoglobin levels. Scandinavian Journal of Haemotology 8(4): 241-244, 1971. (16) JICK, H., GINAN, B., ROTHMAN, K.J. Noncontra- ceptive estrogens and nonfatal inyocardial infarction. Journal of the American Medi- cal Association 239(14): 1407-1408, April 3, 1978. (17) JICK, H., DINAN, B., ROTHMAN, K.J. Oral con- traceptives and nonfatal myocardial infarc- tion. . journal of the American Medical Assoc iation 239(14): 1403-1406, April 3, 1978. 312 TI:~![:N 0048529

(18) KEOTZ, U., AVANT., Q.R., HOYUMPA, A., SCHENKER, S., WILKINSON, Q.R. The effects of age and liver disease on the disposition and elimi- nation of diazepam in adult man. Journal of Ci in ieal Investigation 55: 347-359, February 1975. ; 17, 1977. : (20) PARRY, H.F., SALTER, M.B.,~ MEi.LINGER, Q.D., ous thromboembolism: e usa nd ven t p ti con race v a > > absence of an effect of smoking. British ; Medical Journal 2(6089): 729-730, September ~ CISIN, I.H., MANHEIMER, D.I. National pat- terns of psychotherapeutic drug use. Archives ~ of General Psychiatry 28: 769-783, June ~ 1973. (21 ) PARRY, H.F., CIS1N, I.H. SALTER, M.B., MELLINGER, Q.D., MANHEIMER, D.I. Increasing alcohol intake as a coping mechanism for ; psychic stress. In: Cooperstock, R. : (Editor). Social Aspects and Medical Use of = Psychotropic Drugs. Toronto, Addition ; Research Foundation, 1974. : (22) PFEIFER, H.J., GREENBLATT, D.J. Clinical toxi- city city of theophylline in relation to cigarette ' smoking. Chest 73(4): 455-459, April 1978. ' (23) ROYAL COLLEGE OF GENERAL PRACTITIONERS ORAL ~ CONTRACEPTION STUDY. Mortality among oral : ± ; ` (24) ~ ' (25) ~ a i . 21 (19) LAWSON, D.H., DAVIDSON, J.F., J ICK, H. Oral (26) contraceptive users. Lancet (4): 727-733, Oct ber 8 1977 o . , SARTWELL, P.E. Oral contraceptives and throm- boembolism: boembolism: A further report. American Journal . of Epidemiology 94(3): 192-201, September 1971. SELTZER,' C.G., FRIEDMAN, Q.D., SIEGELAUB, A.B. Smoking and drug consumption in white, black, and oriental men and women. American Journal of Public Health 64(5): 466-473, March 1974. SHAPIRO, S., SLONE, D., ROSENBERG, L., KAUFMAN, D., STOLLEY, P.D., MIETTINEN, O.S. Oral contraceptive use in relation to myocar- dial infarction. Lancet (1 ): 743-747, April 7, 1979. TIMN 0048530

(27) SLONE, D., SHAPIRO, S., ROSENBERG, L., KAUFMAN, D.W., HARTZ, S.C., ROSSI, A.C., STOLLEY, P.D., MIETTINEN O.S. Relation of cigarette smoking to . myocardial .infarction in young women. • New England Journal of Medicine 298(23): 1273-1276, 1978. (28) SWETT, D. Drowisness due to chlorpromazine in relation to cigarette smoking. Archives of General Psychiatry 31: 211-213, August 1974. (29) . U.S. PUBLIC HEALTH. Smoking and Health. A Report of the Surgeon General. U.S. Depart- ment of Health, Education, and Welfare, Public Health Service, Office of the Assis- tant Secretary for Health, Office on Smoking and Health, DHEW Publication ' No. (PHS) 79-50066, 1979, pp.. 1251. (30) WINGERD, J., SPONZILLI, E.E. Concentrations of serum protein fractions in white women: Effects of age, weight, smoking, tonsillec- tomy and other factors. Clinical Chemistry 23(7): 1310-1317, 1977. (31) YEUNG, D.L. Relationships between cigarette smoking, oral contraceptives and plasma vita- mins A, E, C and plasma triglycerides and cholesterol. American Journal of Clinical Nutrition 29:,-,-~ 1216-1221, 1976. 314 TIMN 0048531

: p • PAI,T'!I. ~ .a ; ~ : . BEHAVIORAL ASPECTS OF SMOKIN ; : TIMN 0048532

INTRODUCTION , . . ~ ~ ~. . i . ' ; ..• ! ~ Currently, women are rapidly approaching men in rate of ini- tiation and prevalence of cigarette smoking, but seem to have a• lower rate for successful cessation of smoking. While an increasing percentage of the U.S. population is giving up smoking, nationwide surveys and cessation studies suggest that a smaller proportion of women than men are quitting successfully. This part discusses tobacco use by women, with com- parative reference to men's use wherever appropriate. Special attention is directed to the patterns of initiation, the rise in smoking among girls, and the factors important in the maintenance of smoking behavior including pharmacological effects, smoking patterns, information dissemination, and stress management. The 'differences in successful quitting between men and women smokers are discussed with the hope of generating new Ideas for research and intervention. A separate analysis of' smoking patterns among women in the health professions is presented. A section is devoted to the pregnant smoker because the impact of smoking both on the fetus and the pregnant woman makes pregnancy a period of particular Importance In the life of the woman smoker. INITIATION OF SMOKING IN ADOLESCENT GIRLS Cigarette smoking, particularly cigarette smoking among young girls, Is a changing •phenomenon. Shifts in smoking attitudes and behaviors reflect broader social forces, including changes in sex roles and gender differences in responses to public information programs and to social sanctions against smoking. The trend in adolescent smoking, as in other "aduit- like" behaviors such as alcohol use or sexual activity, is toward earlier onset. For example, before the mid-1970s, girls were less likely to start smoking than boys, and when they did, ~ they started later. Neither of these differences holds true any longer. A number of psychosocial variables correlate highly with adolescent smoking trends. These include the attitudes, perceptions, and behaviors of adolescent girls, their social setting (family, peer groups) and those broad demographic factors (race, education, family income, urbanicity) that help to define an individual's position within the society. 318 , ' TIMN 0048533 .

Concepts of Adolescent Behavior . . ; S : ; . ~ . . ' . > ; .: : .~ , r i a ~ t i Discussion of adolescence with Its attendant problems have seldom differentiated between boys and girls, and no theory or model of adolescent behavior has been developed specifically for girls. However, gender differences in development, cognitive processes, sex-role acquisition and achievement have recently been examined and a number of psychological differencies have been Identified (67, 197, 26, 29, 52, 95). The essence of adolescence is growth, transition, and change. The rate of physical growth in adolescence Is more rapid than at any other stage of development except the neonatal stage. Adolescent development Is a complicated process which involves increasing self-awareness, intellectual and emotional growth, and physiological changes. What adults characterize as risk taking in adolescence may be exploration of the limits of identity and capability. Adolescents are attempting to resolve the competing and conflicting demands stemming from childhood experience on the one hand and expectations of adulthood on the other: dependency and compliance versus autonomy and independent decision making; orientation toward family versus orientation towards peers. They face increasing demands for social and cognitive achievement and for developing the 'self-control required to handle new psychological, physicai,, and social situations. Inadequate experience with these challenges or failure to meet them may result in low self-esteem and increased anxiety and,stress. Numerous formulations contributing to a general model of adolescent development have emerged. These inciude life- span theory and cohort change (125, 53), adolescent sexuality (132), and differences between early and late adolescence (82). Douvan , and Adelson have identified issues - that distinquish adolescence: for girls they are sexuality, interpersonal=intimacy, and identity issues; for boys they are sexuality, autonomy-assertion-independence and identity issues (52). In this study, conducted In the 1950s, girls evidenced conflict between the . social roles for which they were preparing (further education and careers) and the future roles they desired (marriage-motherhood). La Farge described a similar female adolescent conflict between social rules and individual perceptions (105). Research published in the 1970s shows that young women still have role conflicts different from those,of young men (67). 319 , TIMN 0048534

Research on gender-role differentiation in childhood has provided some Insight Into developmental differences between girls and boys. Maccoby ^ suggests that these dif- ferences may derive from different role models for boys and girls; from the *varying responses of significant adults to their beh;viors; from biological differences; and from'a combination of theie (111). Block and Maccoby and jacklin report that the differences include girls having less confidence in their ability to handle a new task and less sense of control over what happens to them (18, 112). Girls also show greater susceptibility to expressed anxiety, greater need for help and reassurance, greater closeness to friends, and more concern for what Is socialEy desirable. Adoiescent behaviors--social or antisocial, adaptive or maladaptive--are a function both of individual choice and of the opportunities for growth and development which- a society provides its • youth (36). 'Not only Is the term 'adolescence' a social definition, but what society perceives as an adolescent problem is also socially defined' (53). Similarly, the development of values, motivations, and controls that foster healthy growth and deter the onset of smoking and other' undesirabie behaviors depends on the opportunities and resources that society makes available'to the adolescent. , ' , . ,.,.., . .. ... . ..... ....,,., ,,, , , Prevalence and Patterns of Adolescent Cigarette Use- Nationat surveys of adolescent smoking behavior have provided Information on gender differences, secular trends, and age subgroupings within 'the adolescent period. Surveys of smoking patterns, ages 12 to 18,• have been conducted -by the National Clearinghouse for Smoking and Health (NCSH) In 1968, 1970, 1972, and 1974 and by the National Institute of Education (NIE) In 1979 (182, 122). Tw® other periodic surveys, both sponsored by the National Institute on Drug Abuse (NIDA), Included cigarette eonsumption (2, 99). A number of studies In specific geographic• locales or among specific populations, such as high, school students, have also been carried out (201). Differing definitions of a current regular adolescent smoker make comparisons among these studies particularly diffieult. In the NCSH and NIE surveys, a regular smoker is defined as one who smokes cigarettes at least weekly. In the NIDA surveys, regular smoking is defined as occurring within the past 30 days. 320 TIMN 0048535

t Prevalence Table 1 summarizes adolescent cigarette smoking prevalence between 1968 and 1979, by age and gender, as surveyed by NCSH and by NIE. Between 1968 and 1974 there was a significant Increase in the percentage of girl smokers in each age category at each point in time, in contrast to the relatively stable prevalence of current regular smoking among boys. A decline in the average age of smoking initiation for both sexes is suggested by the small but significant increase in smoking prevalence among 12 to 14 year olds (186). Trends in the data from a national study of high school seniors also support the hypothesis of an earlier age of initiation (99). In the five years from 1974 to 1979, the proportion of 17 to 18 year old girls who smoked changed little, but the proportion of boys who smoked dropped by a third. It was this difference among 17 to 18 year olds that created the overall higher smoking rate for girls as compared with boys in 1979. However, at ages 15 to 16, the drop from 1974 to 1979 was greater for girls than boys, suggesting that the initiation of -smoking Is also beginning to decline in those girls born after 1962. The differences in the within-age-group changes in the smoking prevalence of girls may represent an isolated effect on the cohort of girls born in 1963 and 1964. The change was essentially confined to the 15 to 16 year old subgroups who were born during these years. The precise nature of the interaction of social influences on the development and maturation of this cohort is unclear. However, other data suggest that a marked secular change occurred in cigarette smoking attitudes and behavior which was secondary to an increased awareness of the health risks of smoking. An alternate hypothesis is that the isolated decline in the 15 to 16 year old subgroup may be an artifact produced by the combined trends of reduced initiation of smoking and the Initiation at a younger age. Thus, the decline in prevalence among 15 to 16 year old girls would reflect the decreasing percentage of young women who are taking up smoking, but this trend will be masked in the younger age group by the tendency of those girls who are going to take up smoking to do so at a younger age. 321 T ~o4g536 -

TABIE 1.-Estimatos of the p.roenta8e of current, regular oi=arette smokers, Adoisso.nts, a=ed 12 to 13, United States, 1968-1979. ' Aeos 12 - 14 Ages 1S- 16 Ages 17 - 18 Ages 12 - 1R Year Maio Female Male Female Male Female Ma1e Female 1968 2.9 0.6 17.0 9.6 30.2 18.6 14.7 8.4 1970 5.7 3.0 19.5 14.4 37.3' 22.8 18.5 11.9 1972 4.6 2.8 17.8 16.3 30.2 25.3 15.7 13.3 1974 4.2 4.9 18.1 20.2 31.0 25.9 1S.A 15.3 1979 3.2 4.3 13.5 11.8 19.3 26.2 10.7 12.7 NdTE: Currsnt regular snaker lna/ud.s respondent who smokos cigarettes at least weekly SOURCE: USDFIEW, 1979 (App.ndix); USDNEW, NIE, 1979 322 , TIMN 0048537

The 1979 NIE Survey reports that: The increasing prevalence of teenage smoking was observed in the period between 1968 and 1968 and 1974 has come to a halt, and a decrease In the smoking rates of both boys and girls has taken place. The decrease in boys' smoking was greater than that of girls, resulting in a higher smoking rate for girls than for boys in 1979. Smoking among boys leveled off in the early 1 970s, and then began to decrease. It appears that girls art. now following this pattern: the smoking rate has leveled off among 17 and 18 year olds, and probably can be expected to decrease over the next few years (122). Other surveys (Table 2) support these trends in ado- lescent girls' smoking behavior. Differences between studies in absolute prevalence rates reported are at least partly due to the differe-nce In the definition a of a smoker, and differences in survey technique. The National Institute on Education (NIE) Survey included as current regular smokers, both those who have smoked one or more cigarettes during'the past week, and those who have smoked less than one cigarette in the past week but more than 100 cigarettes In their lifetime (NIE Survey). The prevalence rates of Abelson, et ai. and Johnston, et al. refer to any cigarette smoking In the past 30 days. The Abelson, et al. data, which were collected 2 years before that of NIE, show the predicted decline but to a lesser degree (2, 122). The Johnston, et ai.'data suggest that there was an increase in adolescent girls' smoking as measured in samples of high school seniors between 1975 and 1977 (99). Johnston's figures were retrospectively reported and refer only to youngsters born before and during 1960 and therefore would not be expected to reflect changes occurring in those cohorts born after 1962 where the decline has occurred. This may explain why the Johnstonis 1977 sample did not reflect a downturn, and reports of iater cohorts of high school seniors should show a stabilization and then a decline In female smoking rates. Results from a study by the same group in 1978 shows the predicted downturn in the smoking habits of high school senior girls (from 39.6 In 1977 to 38.1 in 1978) as wei i as boys (from 36.6 in 1977 to 34.5 in 1978) (99). Age at initiation of smoking. The data In Table 1 show that the prevalence of smoking in girls aged 12-14 increased steadily between 1968 and 1974 to a level equal to or slightly higher than boys of the same age. Between 1974 and 1979 the prevalence of smoking stabilized in girls and may 323 0048538

TA11l.E 2.-Curront usrO of cl3arettes, alcohol and marijuana, by soz: throo natlonal surreys conqarod Ag.i12 - 1• A3es 12 - 17 Aaes 17 - 19 -• NI€. (19791 NIOA. Abelsen, at al. HIE h School Senlors ' j , Ages 12-14 13-16 1977 NIDA. Johnston, e4 al. f13T71 °_• .._. 1974 1979 Ates 1974 1977 197S 1977 Ct1RRENT CIGARETTE USE F 3.1% 4.3% 12-13 13% 10% - M 4.2 3.2 F 21.6 12.3 14-13 23 22 - - M 18.1 14.6 F 26.4 27.0 16-17 38 33 - - M 32.6 19.6 F 11.9 13.1 12-17 F 24 22 F 33.9% 39.6% M 16.3 11.1 M 27 23 M 37.2 36.6•°-- CVRRENf ALQ9H0l. USE 16-17 FlM 31 32 12-17 F 29 23 F 62.2 65.0 12-17 M 39 37 M 75.n 77.8 CIRRENr M4RIJUANA USE 16-17 F&Ik 20 29 12-17 F 11 13 F 22.3 30.0 12-17 M 12 19 M 32.3 40.7 ~ ± 12-1i ? "to:,. Definition of current use varies by.study. Ciiarettes: MIine (1979)- current regular smokor (one or more cisarettes during the past week over and above a mini- nwn five packs) and current occasional smoker (loss than one cigarette per week); Abelson, at al. (1977) and Johnston, at al. (1977)--smoked within the past 30 days. Alcohol and marljuana--ae within tho past month (smokers and nonsmokers). . SOURGES: Abelson, NIOA, at al., 1977; Johnston, NIDA, et at., 1977; NIE, 1979 324 TIMN 0048539

. : : ' : . 0 . 0 have begun to decline. The prevalence of smoking boys of this age peaked .in 1970 and has shown a steady decline since that time. ' These trends may represent fewer adolescents taking up smoking, but those who do beginning at an earlier age. Well over one-half of high school seniors--male and female--who smoke regularly, reported first smoking In the ninth grade or earlier (99). It Is hard to know whether this earlier onset reflects something specific to cigarette smoking or is attributable to the more general pattern of earlier onset of all "aduit-type" behaviors. This trend toward early Initiation of smoking behavior may have a significant impact on the future health of these adoiescents- as many of the health risks associated with smoking Increase with both earlier onset of smoking and duration of the smoking habit. In addition, the earlier the e use of a substance is ..begun, the longer it is likely to be continued and the more heavily It is likely to be used (131, 29, 100). These national surveys do not permit a detailed examination of the initiation process. "Expe•rimenters," those -who have smoked at least a few puffs of a cigarette, but not more than 100 cigarettes, are lumped with "never smokers"-- those who have never taken even a few puffs. "Occasional" smokers are defined as those who smoke less than one cigarette a week but more than 100 cigarettes in a lifetime. In one study, smoking only a few cigarettes usually leads to becoming a regular smoker. Occasional or intermittent smoking Is rare among adults. Examining the proportion of "experimentars" at each age and following their subsequent smoking behavior might help clarify the determinants of the initiation process (120). Their estimate of 8 percent "occasional smoking" in adolescence is based on a definition of smoking less than daily but at least one cigarette a week for as long as 1 month. The difference in definition of occasional smoking makes comparison with current U.S. data on adolesceirts difficult. From 1968 to 1979, the percentage of current occasional smokers (less than once per week) varied between 0.4 percent and 1.6 percent for girls, and 0.4 percent and 2.3 percent for boys (122). McKenneil and Thomas estimated : that the mean length of time between smoking the first ~ cigarette and adopting regular (daily) smoking was slightly less than 3 years for boys and slightly more than 2 years for girls (120). The difference is probably due to earlier . , 325 ; , ~ TIMN 0048540

experimentation among boys. The transition from experimenta1 or occasional smoking to regular smoking is an extremely important one to study because It may provide a crucial period for intervention before psychosocial or pharmacological dependency is established. . Number of cigarettes smoked. In the NCSH/NIE survey, a smaller percentage of girl smokers than boy smokers smoked 10 or more cigarettes per day (61.8 percent versus 73.8 per- cent in 1974, and 59.0 percent versus 65.6 percent in 1979). The high school senior survey showed male-female rates to be equivalent at the haif-pack, per day rate, with boys exceeding girls at heavier levels (99). In that study, the proportion of females -currentty smoking as much as a half-pack per day increased between .1975 and 1977, while the proportion of males smoking at that rate remained constant. The American Cancer Society survey also suggested an increase in the proportion of heavy smokers among adolescent girls compared with stable rates in boys between.1969 and 1975 (203). It reported a fourfold increase in the percentage of girl smokers who smoked at least a pack a day, from 10 percent to 39 percent, compared- with an unchanged rate of -31 percent among boys. The. ' equaiity In . smoking behavior may be extending to the number of cigarettes smoked. 10 mg) is still very small. Type of cigarette smoked. In adolescent smokers of both sexes, there has been a definite trend toward smoking cigarettes with lower "tar" yields between 1974 and 1979. Figure 1 shows the decline In the tar and nicotine levels of the cigarettes smoked by adolescents. Girls appear to be slightly ahead of boys in the use of lower "tar" cigarettes. The trend can be attributed to three factors: the increased marketing of low "tar" cigarettes; the decreased tar levels of existing cigarettes; and increased awareness of differential health hazards associated with different kinds of cigarettes (122). It should be noted, however, that the midpoint on the cumulative percentage continuum has dropped only about 1 mg "tar" between 1974 and 1979, from approximately 17.5 mg to approximately 16.5 mg, and the percentage of adolescents smoking the lowest category of "tar" (less than or equal to 326 TIMN 0048541

i FIGURE 1.-Cumulativra parcant.ye ol.dola.eaot smokers by tha far level ot cbgar.Me aanoked 1974 i 1979 h-* 1974 p 7x 100 90 80J 70 50 N 40 v 30 20 10 ®OYS X i i X ----j( 1979 GIRLS o 1100 r / / / / / / / / / /10 11 13.6 16 i6 i7 18 19 (0.61 (0.81 11.11 0.11 /1.21 11.21 Mg "far° (nnw/ median mq nicotine) SOURCE: Adapled Irom NIE, 1979; fTC, 1978 I 410 (0.81 V . 11,15 16 17 11) 19 >_20 (0.61 I1.1) 11.11 (1.21 /1.31 (1.461 Mg "lar" (and median mg nicotine)

I Smoking cessation. Are there differences between girls and boys in patterns of smoking cessation comparable to those observed in adults? A greater proportion of adult males than adult females have quit smoking (see the section on adult cessation). The national surveys have shown more ex-smokersa among adolescent boys than among girls (122,99). Looking at either the percentage of ex-smokers among all adolescents or at the quit rates (number of former smokers divided by number of ever smokers), boys exceed girls in every survey between 1968 and 1979 (122). For the two most recent surveys, the quit rates were as follows: 33.2 percent of female and 36.0 percent of male smokers had quit in 1974; 30.5 percent of female and 42.3 percent of male smokers had quit In 1979. In contrast, Reeder found no difference in quit rates between boys and girls aged 13-19 in national surveys conducted in 1965 (boys 28 percent, girls 29' percent) and in 1975 (boys 34 percent, girls 35 percent) (141). Thereforey It Is unclear whether adolescent girls show the same patterns of quitting smoking found in adult women. It should also be remembered that research on both smoking cessation and illicit drug use has shown that quitting is often not a permanent state (164, 140, 98). Smoking prevalence and ethnicity. There are no data based on a national sample examining adolescent smoking in different racial groups. ..4iHowever, beginning in 1969-1970 Brunswick has conducted a longitudinal personal home interview survey of a representative sample of 668 urban, non-Hispanic black youths in Harlem, New York City. She found that more 16 to 17 year old girls than boys smoked (62 percent versus 50 percent). This was well before national rates had shown smoking among girls equalling and then exceeding that • among boys. This greater smoking prevalence in girls continued into the young adult years. The same subjects were reinterviewed. 6 to 8 years later, when the youths were aged 18 to 23. Sixty-two percent of young black women * (N = 258) were current smokers and 18 percent were currently smoking at least a pack a day. This Is compared with 57 percent of the black men 18 to 23 years old (N = 277) who were current smokers, 16_ percent of whom regularly smoked at least a pack a day. These prevalence rates are well above the rates for adult black women found in national survey data but are only slightly higher than the rates found in adult black men (201). This study is of substantial interest, but may not be representative of national black adolescent smoking patterns. 328 I

, ro a , . : L Alcohol and marijuana use. Cigarette use should be viewed in the context of"other substanee use behaviors. Abelson, et al., provided Information on the use of other substance in the age range of 12 to 17 by current cigarette smokers and by those not currently smoking (2). Smokers far exceeded nonsmokers in reporting use of alcohol, marijuana and/or hashish, or "stronger" drugs (hallucinogens,. cocaine, heroin, and other opiates). Positive replies for alcohol were. 80.0% versus 44.8%; For marijuana and/or hashish, 68.3 percent versus 16.7 percent; and for stronger drugs, 26.3 percent• versus 4.1 percent respectively (26, 101, 203). Similar figures for alcohol use by 13 to 17 year old girls were reported by Yankelovich, et al., 81 percent of the smok'ers drank compared with 42 percent of nonsmokers, but somewhat lower estimates were reported for marijuana use, 25 percent of the smokers versus 3 percent of the nonsmokers (203). Strong associations between alcohol use and cigarette smoking and/or between marijuana use and cigarette smoking in adolescents and college students have also been Identified in a number of other investigations (83, 94,' 145, 168, 172). . Demographic and Psychosocial Correlates of Smoking in Adolescence. Smoking Is a complex behavior. Adolescents „ start to smoke for multiplee reasons. Strong correlations between , smoking and a number of demographic and psychosocial variables have been reported, but the set of "predisposing factors"• has seldom been subjected to multivarlate analysis. It is rare that more than one or two variables have been tested simultaneously. What appear to be separate determinants of smoking behavior (for example, peer pressure and socioeconomic status) may actually be factors which exacerbate a more basic •variable such as self esteem. A few multiva•riate analyses have been conducted (107, 109, 132). Socioeconomic influences. A number of studies have examined , smoking in relation to socioeconomic status. The findings consistently point 'to a relationship between lower parental status--income and education--and higher smoking prevalence among these parents and their children (20, 122, 141, 151). Adolescents from low-income families may also begin to smoke earlier than others (33, 120). The findings that girls who work have higher rates of smoking may also reflect a 329

relationship to lower economic status (10, 122). Srole and Fischer observed a relationship between downward mobility and smoking in adults (171). , Th-is may be an important dynamic to explore in adolescent initiation of smoking. A relationship between parental education and ado- lescent smoking also exists (122). When one or both parents attended college, 9.9 percent of boys and 10.6 percent of girls smoked, compared with 10.9 percent of boys and 14.8 percent of , girls from homes where neither parent attended college. Family patterns. In single-parent households (19.3 percent of those households surveyed in 1979), adolescent smoking rates were approximately double those of households in which both parents were present (122). This relationship holds for both boys and girls, in every age group, and acros's all five NCSH/NIE surveys; it has also been identified by others (107). In. the 1979 survey, 19.3 percent of the boys and 21.2 percent of the girls in single-parent households are smokers, compared to 8.6 percent and 10.7 percent of those in homes with both parents present. More than one factor is likely to underlie this asso- etation. Adult smoking rates are higher for divorced men and -women. Thus, parental modeling may be involved. Smoking is also Inversely retated to socioeconomic class, and more •single=parent households fall into lower socioeconomic status categories than dual-parent households. Smoking among parents and siblings. Adolescents are more likely to smoke if either or both parents smoke than if they do not (10, 15, 20, 151, 199). (See Table 3.) When both parents smoke, 13.5 percent of sons and 15.1 percent of daughters smoke; when one parent smokes, 9.1 percent of the boys and 12.7 percent of girls smoke; and in homes where neither parent smokes., 5.6 percent of boys and 6.5 percent of girls smoke (122). There are conflicting reports on the relationship bet- ween the sex of the smoking parent and smoking habits of the offspring. In two-parent homes in which only one parent smokes, 17 to 18 year olds appear to be more likely to smoke if the mother does (122). Other studies have identified a relationship between the child's smoking and that of the parent of the same sex (15, 199, 10). Allegrante, et ai., found a relationship between the mother's smoking behavior and that of sons, but not of daughters, and no 330 TIMN 0048545

, ...y:.•... •'.~• :. b. .. ..•J'tr r . .•.y.. . .a•. . . .. .:•.•...~•.r.'•.e . o..~,...~:.-. ...a•...~~..r•:we..r...r+rsr .. s r . . . . .. . TABLE 3.-Percentage of adolescents who smoke by the smoking behavior of parents and older siblings Have No Older Sibiing Have Older Sibling One/8oth Neither Parents Smoke Parent Smokes One or Both Parents Smoke Neither Parent Smokes , Older Sibling Smokes No Older Sibling Smokes Older Sibling Smokes No Older Sibling Smokes Boys: 12-14 2.8 0.0 6.3• 2.7 0.0 0.0 w ' 15-16 17.6 4.0 18.8 6.3 21.1 2.1 " 17-18 15.0 . 7.9 25.4 16.7 31.7 0.0 Totai 8.2 2.9 17.0 7.5 19.5 0.6 Girls: 12-14 3.7 0.0 815 1.3 3.4 2.9 15-16 8.2 5.7 20.0 13.0 15.2 2.4 17-18 29.7 15.4 32.9 19.6 25.0 6.7 Total 9.7 4.1 20.3 9.7 15.3 4.1 BASE: Both Parents Present in Household SOURCE: NIE, 1979

a relationship of the father's smoking behavior to children of either sex (3). In contrast to all of these findings, Schneider, et al., were , unable to relate parental smoking to that of offspring (156). Explanations for the _ association between parental and children's smoking behavior include the effect of role- modeling, parental permissiveness (real or imagined), and availability of cigarettes in the home (119). Older siblings seem equally important or more impor- tant than parents as potential role models for smoking (10, 122, 141). There Is a greater likelihood that an adolescent will smoke if one or more older siblings smoke than if no older siblings smoke; this is true in those households where neither parent smokes as well as in those where one or both parents smoke. In the 1979 survey, boys with, older siblings who smoke were more than three times as likely to smoke as boys with nonsmoking older siblings. The increase is about twofold for girls (see Table 3). The highest smoking rate for girls was found when at least one parent and an older sibling smoked (20.3 percent). The corresponding rate for boys (17.0 percent) was slightly lower than where an older sibling but neither parent smoked (19.5 percent). Peer group Influence. Adolescents' smoking behavior is highly correlated with reports of having friends who also smoke (15, 126, 127, 147, 152, 203). Most multivariate analyses have established this factor as being of prime importance although one such analysis found no relationship at all (109, 132, 3). It has been pointed out •that patterns of drug use in adolescents are very similar among best friends (121 ). It has not been demonstrated, however, that it is the behavior of friends rather than Inclinations of the adolescent which influences him or her to smoke (3, 122, 156). lnquiring about the smoking behavior of the "four best friends" of adoiescent respondents, the NIE study reported that 87.6 percent of boys and 94.0 percent of girls who smoked stated that at least one of those friends also smoked. In addition, only 10.2 percent of boys and 5.9 percent• of girls who smoked had no regular smokers among their four best friends, and an even smaller fraction (2.2 percent of boys and 0 percent of girls) reported that none of their friends had even experimented. In a parallel vein, it was found , that nonsmokers also congregate together. Approximately one-third of the nonsmokers (33.8 percent of boys, 32.9 percent of girls) reported having at least one best 332 TIMN 0048547

~ ; ;.' . ~ { ~ . ; ~ j ' ~ ' .; ; 1 ~ ; ; ; , ; ~ ~ : friend who smoked, while over two-fifths (43.0 percent of boys, 44.1 percent of girls) had no best friend who smoked regularly. Over •-one-fifth (22.4 percent of boys, 23.0 percent of girls) had no best friends who had even experimented. Thus, "peer pressure" to smoke may be operative when the adolescent belongs to or would like to belong to a group In which smoking is part of the life-style, (122). When' the neer group behavior does not include smoking, there may 'be little pressure on the adolescent to begin to smoke. Conformity pressures and peer influence are very strong In early adoiescence. Therefore, IT smoking were considered a behavior which was adopted by the majority of adolescents, experimentation and initiation might occur because of the, importance of conformity in this age period (63). Unfortunately, there are suggestions that most adolescents tend to overestimate the proportion of their peers who are smokers. Eighty-two percent of all girls surveyed in the smoke (72 - percent), compare w g g percent) (203). Similar percentages apply to the fraction of all male friends who smoke (69 percent for girl smokers and 32 percent for nonsmokers). Yet girls are less likely than boys to see smoking as a social asset (37 percent versus 55 percent) and they even consider it a drawback (52 percent girls versus '31 percent boys). The kinds of images projected by the people shown in -cigarette advertisements may support to peer influences to smoke. Girl smokers characterized such people as attractive (69 percent), enjoying themselves (66 percent), well-dressed (66 percent), sexy (54 percent), young (50 percent), and healthy (49 percent). Prevention efforts aimed at making actual statistics on smoking prevalence available to teens in order to correct the above beliefs may help counter the advertising. Popular personages in various professions • and lifestyles which girls mistakenly perceive as smoker-dominated could be recruited in this effort. 333 1975 American Cancer Society Survey thought of adolescents as smokers rather than nonsmokers (203). In that same' survey, the professions of teachers, executives, housewives, and feminist leaders were all characterized as smokers by approximately two-thirds of girls, with only doctors and athletes considered nonsmokers. _ Heterosexual peer considerations may also be important. Girl smokers are very likely to have boyfriends who also d itfi nonsmokin irls (27 TIMN 0048548

Scholastic achievement and aspirations. Achievement In school 'has been one of the,t most frequently investigated correlates of smoking, with a study as early as 1923 showing an association between poor school grades and smoking (15, 81, 11.5, 31, 151, 198, 137). Two studies have reported this ,association specifically for girls (35, 203). Comparing the three factors--parental-smoking, socioeconomic status, and scholastic performance--Borland and Rudolph identified scho- lastic performance as the strongest correlate of smoking in a sample of high school students (20). Studies of achievement, aspirations and expectations in relation to smoking have found that reduced motivation and lower aspiration are found that reduced motivation and lower aspiration are associated with a higher prevalence of smoking (3, 33, 99, 122). High school students In college preparatory courses were far less likely to smoke than students in any other type of curriculum (122). Smoking rates for boys and girls preparing for college (9.0~ percent and 12.0 percent, respectively) were 50 to 60 percent t ; of those In other curricula (18.3 percent of boys, 20.1 percent of girls). The same trend was found in a previous study (193). Smokers are iess involved in extracurricular school activities and have a higher rate. of absenteism (3, 10, 35, 131). •These factors are undoubtedly interrelated with social class and other.factors. Sense of competency and sense of efficacy (or personal control) are linked to school achieve- ment. Smokers have been reported to have less confidence that they- can control what they will become (122). McAlister, et al., comment that high academic achievement is probably also associated with admission into a peer group in which smoking is not accepted (119). Furthermore, they state, "Educationally deprived young people may be somewhat less aware of the risks of smoking, but they also experience more stress and greater pressure to adopt behaviors that signal independence and maturityn (119). Dynamic/personality factors. Up to this point, adolescent smoking has been described and analyzed in terms of discrete variables, many of which are truly not independent of one anothdr. From them, a composite picture of the environment of the girl smoker begins to emerge. Also there is a set of individual/personality factors which relate the adolescent to the world around her. These include attitudes, values, beliefs, feelings of self-worth, aspirations and expectations for the future, and perceptions of efficacy, competence and the girl's view of her own smoking behavior. 334 ' TIMN 0048549

Yankelovich, et ai. have provided a thought-provoking description of the evolution in values which has occurred over the past 20 years (203). Smoking is just one behavior which may have been "suppressed" by social norms describing appropriate behavior for women in the past, and which now may be "disinhibited" in a very real sense. Accompanying this shift in sanctions on female behavior is an increase in expressed rebelliousness among girl smokers, which was formerly more characteristic of boys. A higher percentage of girl smokers than nonsmokers are annoyed by "experts" who define what is good for them (53 percent versus 34 percent), agree that there is too much regulation of people's lives (50 percent versus 39 percent), and do not want to follow their parent's wishes regarding their behavior (almost 50 percent versus 26 percent) (203). Factor scores of boy and girl smokers similarly reflect a more negative "feeling toward authority" or dislike of adult-imposed restrictions than those of nonsmokers, and are approximately equal for both sexes (122). Clausen noted that girls who smoked were less acquiescent to their parents, more autonomous, and "strikingly higher in quest for power" than nonsmoking girls (33). The evolution in values and sex-role behaviors has resulted in some interesting differences between boy and girl smokers, (203). The boy smoker remains more socially uneasy, expresses a greater need to be popular with the opposite sex; and considers smoking more of a social asset than the girl smoker. The girl smoker, compared with her nonsmoking peer, is more likely to consider parties a favorite leisure time activity, to have a boyfriend, and to have had sexual relationships. In addition, she is less likely to feel nervous meeting new people. Finally, while she is- more wiiting to admit that smoking is a drawback, she shows less acceptance than the boy smoker of the stereotype that adolescents begin to smoke cigarettes to gain peer acceptance and approval (122). Nonsmokers show the greatest acceptance of this stereotype and the one which describes the smoker as a°show-off" who believes that smoking makes one look "cool" or "grown-up." In other studies of smoking behavior, self-esteem has usually been investigated in terms of the adolescent's self- confidence in interpersonal relationships. Smoking is ego enhancing and facilitates social functioning (116). This -has been observed specifically among adolescent girls and female 335

undergraduates who smoke (203, 163). Smoking is correlated with a wish to be older (122). Both boys and girls who differed from, the norms of their high school peers on tests of self-concept were more likely to smoke cigarettes as well as to use other drugs (92). Adolescent smoking has been consistently correlated with low educational and occupational aspirations. In a review which included Niocus of control" as a measured variable, Smith concluded that smokers were more externally oriented and felt that they had limited control over what happened to them (167). Pflaum reviewed findings on the positive relationship between smoking and feelings of helplessness and hopelessness (137). Adolescent smokers express less desire and ability than nonsmokers to control future events, for example, to determine what kind of person they will become (122). Girls scored slightly higher than boys on this factor, Indicating a greater sense of future control. Finally, response to stress has been suggested as a basic dynamic in cigarette smoking (116). Feelings of unattractiveness, a sense of incompetency and inefficacy in school achievement and personal relations, limited opportunities for personal growth and for future social and economic roles all contribute to stress in adolescence. Changes in social settings, such as transition from elementary to junior high school, which occur simultaneously with physical -and emotional changes must also be acknowleii;ed. Theoretical formulations of life-change events and their effects on health might also be worth considering in studying the onset of cigarette smoking among g:ris (49). Prediction of Future Smoking Behavior. In 1979, a longitu-. dinal study was undertaken by the National Institute of Education involving the re-interview, of 46.8 percent (N = 1194) of the 2,553• adoSescents first surveyed in 1974 (122). In 1974, 152 respondents were smokers and 1,042 were nonsmokers. By 1979, 27 percent (N = 41) of the smokers had quit, while 73 percent (N = 111) had continued to smoke. During the same time period, 20.8 percent (N = 217) of the nonsmokers had taken up smoking, while 79.2 percent (N = 825) had not. Thus, the proportion of smokers who had quit was greater than the proportion of nonsmokers who had taken up the habit. However, because the percentage of nonsmokers was much higher than the percentage of smokers the net effect was an increase in the percentage of the population who were smokers (12.7% to 27.5%). 336 551

)ehavior was ture smoking With eaah 'increase in age group, the proportion of boys who initiated smoking became smalier, so that boys who reached age 17 or 18 as nonsmokers were not likely to start in the next five years. Only 15.4 percent did so, compared with 19.3 per=ent of 15 to 16 year olds, and 21.6 percent of 12 to 14 yeae olds. For girls, the pattern is less clear. Fifteen to 1;', year old nonsmokers in 1974 showed thee greatest propotion of initiators (27.1 percent) by 1979. In the 12 to 14 age group, 22.8 percent took up smoking, and only 14.7 percent in the 17 to 18 age group did so. Demogr-,phic and psychosocial relationships studied in 1974 were ree Kamined in this group now aged 17 to 23. The influence of -dder siblings became less powerful than the Influence of peers, but educational attainment was still inversely correlated with smoking status. Those -mokers who had quit had a shorter lifetime history of smoking and were lighter smokers than those who were current smokers in 1979. Of the. former smokers, 24.7 percent said they had been smoking less than daily just before quitting, and ?nother 34.5 percent smoked 1 to 14 cigarettes per day. Onl r 7.6 percent of current smokers report less than daily consumption. This suggests that the former smokers may have been less dependent (psychologically or physiologically) upon cigarettes and may have found giving up the habit easier than heavier smokers. In fact, 50 percent of the former s,-iokers succeeded in quitting on their first attempt, while 61.6 percent of current smokers had made one or more unsuccessful attempts to quit. These ;oung smokers were concerned about health issues. Sixty percent of current smokers had made at least one attempt, agid another 20 percent would have been willing to quit if ther . was an easy way to do so. A greater per- centage of yo-ng women than men (91.0 percent and 85.2 percent, respectively) expressed a concern about health effects of smoking. The risk associated with oral contra- ceptive use and smoking and the harmful effects on the fetus or by smoking during pregnancy (122) may be responsible for this increased concern. , Young women were more likely than young men to say that all cigarettes are equally hazardous (33.7 percent and 25.9 percent, respectively). Multiple regression analysis was used to Identify those adolescents mo-t likely to take up smoking and discriminant function analys:s were used to predict future smoking for each stage--noi ismoker, experimenter, regular smoker, and ex- 337 for never- )Ider sibling, ince that a ie nonsmoker iitiated, the asp i rat ions, f the health avior. •mer smokers ular smokers. r dosage and smokers, on :rest in doing sociated with to accurately vas also more d peers. And ts were lower ; FOR FUTURE are a number prevent the 186). These igh, and high . approach to ormation about in coping and influences in iures, parental tors are often self-reporting f physiological tine or expired e analyzed for health risks of i a superficial (and 91.6 per- 11 - TIMN 0048552

s ; , , . . cent of smokers) "strongly or mildly agreed" that smoking is harmful to health (122). Percentages were similar for boys and girls, and nonsmokers scored higher on all health-related questions than smokers. Almost ninety percent of adolescent smokers (87.9 percent of boys and 89.9 percent of girls) "strongly or mildly agreed" with the statement, "I believe the health information about smoking is true." Fishbein has pointed out, however, the potential importance of the• difference between strong and mild agreement with such statements, and the lack of direct personal attribution involved (63). Oniy 60 to 65 percent of adolescent smokers expressed strong agreement, compared with approximately 80 percent of nonsmokers. Either reduction of cognitive dissonance by denial or actual lack of information may underlie this response pattern. Finally, a surprisingly high percentage of smokers feel (strongly or mildly agree) that It is al i right to ,smoke if "you don't smoke too many." On this item, fewer girls (25.6 percent) were willing to endorse this statement than boys (43.3 percent). Somewhat lower estimaies of the acceptance of health information comes from the , 1975 American Cancer Society Survey (ACS) (203). Of all ado-tescent girls 74 percent agree that smoking is as harmful for women as It is for men; 7lpercent agree that smoking Is harmful for young peopie as well as for older people; 56 percent agree that it is not safe to smoke low "tar" cigarettes; and 56 percent agree that smoking is as addictive as illegal drugs. Comparable figures are not provided for boys, nor are the data broken down by smoking and nonsmoking categories. This survey further reports that 68 percent of the girl sample was not warned about smoking by their doctors. While 60 percent of girl smokers began to smoke before the -age of 13, only 48 percent attended an anti- smoking education program in school, and a. mere 4 percent attended such a program in the sixth grade when they were approximately 12 years old. These statistics suggest that smoking education and coping strategies should begin earlier in schools and should begin earliest for high risk groups. Research og ais. The best evidence suggests that female ciga smoking rates are declining. This change has occurred in more recent adolescent cohorts--those born after 1962. Nationai surveys are likely to underestimate true rates 339 TIMN 0048553

whether school, household, or telephone samples are used. Drop-out, absenteeism, lack of telephone accessibility, and belonging to a minority group all contribute to the sampling errors, which inciude underrepresentation of population subgroups whose rates are substantially higher than the norm. Accurately measuring these subgroups would enable scientists to better target interventions. Young black females appear to be , one such group whose smoking rates well exceed the national average. There is good reason to expect the heaviest cigarette use and other "problem behaviors" among those segments of the adolescent population who feel cut• off from socioeconomic opportunity and mobility. The review of correlates of adolescent smoking shows that many of the variables that predict cigarette smoking bear a remarkable similarity to ones identified as predictors of marijuana and/or other illicit drug use. It. is recommended that greater attention be given to models of behavior and socialization processes. More prospective longitudinal studies need to be undertaken, based on varied samples of children. Data need to be collected about physical and emotional status, psycho- social outlooks and attitudes, family and peer relations, academic and , recreational activities, family and school set- tings, and family and residential background. This information must be gathered early in childhood to record significant socialization inftuences which precede the onset of smoking behaviors and should be collected frequently enough to record •significant changes close to the time they occur. MAINTENANCE OF SMOKING SMOKING BEHAVIOR Patterns of cigarette smoking. SmoKing patterns differ between the sexes. •Schulz & Seehofer studied the smoking behavior In male and female smokers observed surreptitiously , in public places. 'Puff number, duration and interval were measured (157). Women were found to leave a significantly longer butt length (approximately 2 mm longer) and had shorter puff durations than men (see Table 4). However, they took a greater number of puffs and, therefore, had the same total puff duration (puff number x puff duration). These authors do not report gender data on inhaiation patterns, which are crucial to determining dose. Creighton & Lewis reported no sex differences in puff volume in a small study of the inhalation patterns of eight men and eight women (39). 340

TABLE 4.-Smoking parameters observed In Hamburg, Germany tn 1971 and 1974 ~ Puff Number Puff Duration (sec) Puff Interval (sec) Total Puff Duration (sec) 1971 1974 1971 1~Q74 1971 - 1974 1971 1974 Men 10.2 10.9 1.47 1.47 52.9 42.1 15.0 16.0 Women 10.9 13.3 1.31 1.17 46.0 40.7 14.3 15.5 AII 10.5 11•.8 1.41 1.34 50.3 41.5 14.R 15.8 SOURCE: Schulz and Seehofer, 1978. i

Data on smoking patterns were collected in surveys conducted in 1964, 1966, 1970 and 1975 by the National Clearinghouse for Smoking and Health (see Table 5). In each survey a greater proportion of men than women reported inhaling deeply into the chest and inhaling almost every puff. Men therefore may extract a greater dose of nicotine and the other constituents of cigarette smoke than women do. However, there Is an increasing proportion of women who report smoking their cigarettes "as far as possible," in contrast to a decline in the proportion of men who reported this behavior (157). A slightly higher proportion of males reported letting "very little" of their cigarette burn without smoking it: 1970, 20.6 percent male vs. 18.0 percent female; 1975, 20.9 percent vs. 18.6 percent female (181,182). These changes are often a correlate of heavier smoking. in sum, the observational data suggest that men and women have equal total duration of smoking per cigarette, and the national survey data suggest a larger proportion of males inhale deeply. In general, men smoke in a more hazardous way than do women. However, the smoking patterns of women are changing toward "more hazardous" smoking (see Part I of this Report). In contrast to the minor changes that have occurred in the way an tndividuai cigarette is smoked, there have been substantial changes in the percentage of both male and female smokers who smoke more than a pack per day (Table 6). A number of explanations may be offered for the data in these two tables, (186): (1) more lighter than heavier smokers may be quitting, resulting in a mean increase in daily consumption; (2) continuing smokers may be increasing consumption; (3) smokers newly initiating the behavior may be smoking more heavily than alrtnv!V established smokers; and (4) declining tar and nicotine contents of cigarettes may be leading to compensatory increases in number of cigarettes smoked In order to maintain nicotine dosage. The 1975 survey reported a greater percentage of women smokers smoke filter tip cigarettes, 90.6 percent of women smokers versus 79.3 percent of men smokers. Women also seem to be less fixed in their brand preference. Sixty- one percent of women and only 10 percent of men acknowledge changing brands at least once, and women lead the trend in adopting king-size, filter-tip and 100 mm cigarettes. On the other hand, women smoke cigarettes almost exclusively. Cigars and pipes are currently used by z 342 TIIV1VCl~r 0048556 -

"r TABLE 5.-Respondent-reported styles of cigarette smoking, current, regular cigarette smokers, selected categories, adults, United States, 1964-1975 . 1964 w 4- w 1966 1970 1975 Male Female Male Female Male Female Male Fernale 1. Inhaling deeply lnto the chest 36.5% 22.5% 31.8% 15.5% 34.3% 17.50A 30.3% 16.4Y, 2. Inhaling almost every puff 63.1 54.8 63.0 52.1 60.5 47.2 58.5 50.7 3. Smoking cigarette as far as poss161e 15.9. 7.5 13.5 10.0 9.6 10.4 10.9 12.9 1. In 1964 and 1966, the questlonnaire response was 'as deeply Into the chest as possible.." In 1970 and 1975, the questionnaire response was phrased 'deeply into the chest.a 2. In each survey year, the questionnaire response was "Inhale almost every puff of each clgarette. 3. In 1964 and 1966, the respondent was asked to draw a line on a diagram of a cigarette, indl- cating the average length of the discarded cigarette butt length. In 1970 and 1975 the verbal questionnaire response was smoking cigarette as far as possible. The data for 1964 and 1966 pcorrespond to those respondents Indicating a discarded cigarette butt length no greater than 20 nm. ? SOURCF: USI)HEW, 1979a, Appendix.

C TAdLH 6.-Estimates of the percentaee of current, regular cl`auette tmokors who consume more than one pacYk per day, adults. United States, 1935-1976. Supplement to Current Health Interview Nat/onal Clearinghouse Population Survey Survey for Smokin8 and Health (17 yrs. and over) (17 yrs. and over) (21 yrs. and over) 21 clgaret/es or 25 cijarettes or 25 cigarettes or more daily moro daily nwre daily Year Total Ma1e Female Total Male Female Total Male Female 1955 20.21 25.5 9.8 1964 25.7 32.4 17.7 1965 19.9 24.5 13.7 1966 21.6 26.3 15.7 27.2 34.7 16.9 1967 21.9 26.2 16.3 1968 22.4 - '26.5 16.8 1970 23.3 27.6 18.1 25.2 31.1 17.1 1974 24.72 30.3 18.4 1975 30.1 36.0 22.8 1976 25.33 30.8 19.4 118 years and over. 2Qata provided by Health /ntervlew Survey, National Center for Health Statistics. 320 years and over. SOURCE: USfk1EW, 1979, Appendix.

10.3 percent and 7.2 percent of men, respectively, but by less than 0.5 percent of women. Only 1 percent of women use snuff or chewing tobacco compared with 3 percent and 5 percent of men, respectively. Smoking prevalence and athnicity. The prevalence of smoking ' In the population varies not only with age, sex, and ' socioeconomic status, but also with race and cultural ' background. Table 7 presents smoking prevalence among white and ~ black adults from 1965 to 1978 (186, 187). Smoking has ; declined among men of both races, but prevalence has ; decreased only slightly among white and black females. ~ Congruent estimates of prevalence and lower cessation rates - • among blacks have been obtained in other studies, s (66,174,190). . ~ , Despite their greater prevalence of smoking, black men and women smoke fewer cigarettes per day than whites (66,174). Black women may suffer the worst aspects of sexism and racism with respect to occupational opportunity and financial compensation. Cigarette smoking may be related to assertion, independence, and rebellion or to identification with behavioral patterns of black males. Adolescent dynamics have been studied more than those of adults (see adolescent Section I). Warnecke et al., found that social and psychological correlates among black women are similar to those observed among white women (190). Friedman, et al. examined smoking prevalence among Oriental men and women--Chinese, Japanese, Korean or unknown from the Kaiser Permanent Health Plan and found a smaller percentage of cigarette smokers than among whites or blacks. Asian women had the least frequency of current, ; established cigarette smokers--23.1 percent--compared to 39.2 percent of white women and 42.1• percent of black ~ women. Asian were also the least likely to inhale among most age-sex groups of smokers. There were fewer cigarette ; smokers among Chinese than among Japanese; this was , particularly true for women and younger men. Pharmacological Effects of Smoking One or more of the constitutents of cigarette smoke may play a role in the maintenance of smoking behavior and help 345 TIMN 0048559

Table 7.-Estimates of the percentage of current, regular cigarette smokers among white and black adults, aged 20 years and over, United States, 1965-1978. I White Plack Year Maie Female Maie Female 1965 51.5 34.2 60.8 34.4 . 1970 43.7 31.9 54.0 33.1 1974 41.9 31.8 55.3 36.8 1976 41.2 31.8 50.5 35.1 1978 36.4 30.1 42.8 30.2 Note: Results displayed as percentage of respondents with known smoking status ages 17 years and over. SOURCE: National Center for Health Statistics: USpHEW, 1979, Appendix.

-r account for the difficulties many individuals experience when they try to quit smoking (186). Nicotine. Nicotine is absorbed rapidly from the oral and intestinal mucosa, lungs, and skin. It is distributed throughout the body and Is metabolized by several organs, including the liver. It is then rapidly cleared, primarily through the kidney. Nicotine has effects on several organ systems, * Including the autonomic nervous system, voluntary muscles, stomach, intestines,. heart, and brain. Most of the pharmacological actions of nicotine are thought to result from its interaction with receptors of cholinergic nervous systems. Analysis of the physiological effects of nicotine is complicated by the abundance of those effects. Many organs receive input from several neuronal systems which are altered directly or indirectly by cholinergic activity. Furthermore, the effects of nicotine itself depend both on the dose and on the time course of drug, administration: brief exposure or low doses cause excitation of cholinergic systems, while long exposure and high doses result In inhibition and paralysis. Peripheral Effects. Nicotine produces a variety of changes in the autonomic nervous system due to simultaneous effects on both sympathetic and parasympathetic systems. The end result is an increased heart rate and blood pressure; cold, clammy skin; increased acid production in the stomach; increased intestinal activity; and biphasic changes in salivation, with an initial Increase followed by a decrease. Nicotine also Increases respiration. Central Effects. Nicotine produces tremors and causes water retention by a central effect on antidiuretic hormone release. Nicotine-induced nausea and vomiting reflect a complex interaction between central and peripheral effects. To date, no specific effects on complex emotions and beha- viors have been demonstrated. Animals will self-administer nicotine under certain circumstances, indicating that it may have pleasurable effects. A Possible Role for Nicotine in Smoking Maintenance. A strong argument has been made for classifying smoking as an addiction, with nicotine as the leading candidate for the 347 TIMN 0048561

addictive agent (124). inhalation of cigarette smoke offers an effective way to administer nicotine. Absorbed rapidly, it travels as a highly concentrated bolus through the heart and directly to the brain and is then rapidly cleared. A smoker who smokes one pack per day can average around 70,000 such nicotine "injections" per year. In behavioral terms, smoking has many potential conditioned stimuli, ranging from the taste, sight, and feel of the cigarette itself, to the many social settings In which smoking takes place. If nicotine were a strong unconditioned stimulus, particularly when inhaled, then it would be easily understandable that smoking can become a remarkably persistent habit through connection of this unconditioned stimulus with the many associated stimuli. Direct proof for nicotine as an addictive agent remains scant. Recent studies do demonstrate that some animals can be induced to self-administer nicotine In carefully controlled settings. Depending upon the conditions selected, this self- administration can be either a negative or a positive stimulus to the animals. Studies of humans have shown that smokers will modulate their cigarette intake slightly to alter serum nicotine concentrations, particularly when levels get too high. These studies failed to show that intravenous infections of nicotine have pronounced effects on reducing smoking, suggesting that nicotine is not the only important factor. Some have suggested that nicotine controls smoking behavior only at the extremes, and then as an aversive agent (153). Too much smoking might lead to such high serum concentrations of niVotine that toxic effects encourage tower tntake; and too little smoking or smoking of low-nicotine cigarettes could lead to such low concentrations that withdrawal side effects encourage resumption of smoking. This hypothesis states that, between those two extremes, other factors such as psychological and social pressures are far more Influential In determining smoking patterns. Although nicotine has effects on essentially all major organs in the body, tncluding the brain, the role of those actions in maintaining the smoking habit remains an important but unresolved area of research. The nicotine hypothesis of smoking is that the phar- macological actions of nicotine are "reinforcing.R The most likely site of this rewarding or reinforcing action is the brain, with the precise locus of reinforcement not yet determined. Inhaling smoke insures rapid delivery of nicotine to the brain. It takes approximately 13.5 seconds for an Intravenous injection of nicotine in the arm to reach the 348 62 I-MN u0485 T

i , : s brain; but by inhalation, the delivery time is 7.5 seconds (149). The plasma half-life of nicotine is approximately 30 minutes, and the pack-a-day smoker lights up approximately every 30 to 40 minutes of the day. This suggests that the smoker is attempting to maintain a constant level of nicotine. The nature of the reinforcing effect is sometimes described as an alteration of arousal. Stimulation may be subjectively experienced as increased alertness, a facilitation of concentration, or an aid to continued efficient performance in fatiguing tasks. Sedation, on the other hand, may be experienced as a tranquilizing or calming effect or as a reduction of some dysphoric state, such as anger. Smoking has been described as distinctly pleasurable following a meal or accompanying xanthines (coffee and tea) or alcohol. Pharmacologic and psychologic components to these subjective reports are beginning to be identified (76, 69). There is an' extensive literature describing acute and chronic nicotine administration in animals including a limited number of self-administration models. Tolerance to nicotine has also been described (108, 79, 84). A number of studies have examined the hypothesis that humans self-administer tobacco In order to obtain nicotine. Studies have also examined compensatory adjustments in the number of cigarettes and manner of smoking by subjects in response to experimenter-induced increases or decreases in cigarette nicotine content, cigarette size, availability, or supplemental nicotine administration. Chewing gum containing nicotine, nicotine tablets, intravenous nicotine and central or peripheral nicotinic blocking agents have been used to supplement or block the effects of the nicotine absorbed from tha smoke. A titration effect is said to occur if subjects change their cigarette smoke intake in the appropriate direction in response to these experimental manipulations. A modest amount of compensation has usually been demonstrated (149, 77). Smokers seem to titrate smoking by the nicotine, rather than the tar. Experiments involving the intravenous administration of nicotine have been inconclusive with both positive and negative effects on the suppression of subsequent smoking having been observed. When compensation occurs, it is seldom complete. This may be due to a number of factors: (1) the inability to accurately measure the smoke and/or nicotine dose delivered to the subject; (2) technical problems in experimental design (77, 186); (3) secondary reinforcing effects of smoking which mask titration; and (4) the fact that people may smoke for reasons other than regulation of nicotine level. ' 349 ; . TININ 048563 --

Differences in nicotine metabolism. The metabolism of nico- tine may be different in men and women. Measurement of nicotine and cotinine (the principal metabolite of nicotine) excreted in the urine after intravenous administration of nicotine hydrogen tartrate suggested differences in metabolism based on sex and smoking status (171). In nonsmokers, men excreted less nicotine but more cotinine than women, suggesting greater initial metabolism among men. However, there were no clear differences between male and female smokers. Schievelbein, et al., studied nicotine and cotinine excretion in both regular smokers and nonsmokers after they smoked cigarettes with differing tar and nicotine levels (155). Women excreted significantly lower amounts of nicotine and cotinine compared with men for three of the four brands tested. The gender difference was found for the excretion of nicotine and cotinine when tested separately and together. The number of cigarettes smoked per day did not differ between the - sexes, but the carboxyhemoglobin (COHb) levels were lower in the women and COHb levels are often taken as a correlate of depth of inhalation. The female subjects, therefore, may have received a lower dose of nicotine because of a different smoking pattern. Smoking and Stimulation Effects The literature suggests that women are more likely to smoke in situations of high arousal than low arousal and when experiencing "negative affect" (68, 93). The effects of smoking, which are often perceived as tranquilizing, might then be sought as a major coping mechanism. However, it can also be argued that the stimulant effects of nicotine, which are usually considered the predominant central nervous system action, might be equally useful as a mobilizer. These related and commonly held beliefs will be examined in some depth. Frith (68) studied British male and female employees in a psychiatric institute; they ranged in -age from 28 to 50. Subjects rated the strength of the desire to smoke in 22 hypothetical situations. The 12 high-arousal items involved either emotional strain and anxiety or demanding mental activity; the ten low-arousal items concerned boredom and relaxation or repetitive tasks and physical fatigue. A factor analysis of the entire questionnaire and t-tests performed on male versus female scores for the most extreme situations on the continuum led Frith to state that men had a greater desire to smoke in situations inducing boredom and tiredness 350 TIMN 0048564

: , showed two films, one intended to evoke positive affect (a slapstick comedy), and another to evoke negative affect (a and women had a greater desire to smoke in stress-inducing situations. However, men rated the desire to smoKe significantly higher than did women on all three of the questions representing low-arousal situations, whereas women rated the desire to smoke significantly higher on only one of the three questions representing the high-arousal extreme of the continuum (68). Using Frith's questionnaire, Barnes & Fishlinsky were unable to replicate his findings In a sample of Canadian undergraduates (13). Within the male sample, there was no significant relationship between desire to smoke and the arousal value of the situation in the question, and female subjects indicated a greater . desire to smoke in the low- arousal situations. The authors point out the possible importance of sampling differences. Elgerot studied light, medium, and heavy smokers in an attempt to control potential differences in inhalation patterns between men and women (cited by Frith as a possible explanation for his results) (58). Subjects were Swedish university students. The 42-Item questionnaire was similar, but not identical, to Frith's. There was no gender difference for low-arousal situations. There was no sex difference in the light and medium smoker subgroups, but women in the heavy smokers subgroup expressed a greater desire to smoke in stress-inducing circumstances. Russell and his colleagues devised a 34-item questionnaire covering a wide variety of smoking motives. It was administered to 175 normal smokers and then subjected to factor analysis (150). Six factors, representing six types of smoking, were identified. Women scored significantly lower on what was termed "sensorimotor" smoking, and significantly higher on "sedative" smoking. Thus, the sex difference on sedative smoking (reduction of arousal) was supported. Ikard and Tomkins (93) found evidence that women smoke in situations involving negative affect. Negative affect smoking Is defined as smoking which serves to reduce unpleasant feetings. It includes smoking to reduce the dysphoric feelings accompanying rejection by a social group as well as smoking to satisfy a craving for a cigarette (i.e., a deprivation negative affect). Positive affect smoking involves the arousal of pleasant feelings. For example, smoking from curiosity would be classified this way because of the feelings of excitement and interest generated. Ikard and Tomkirts 351

documentary on Nazi atrocities) to college students who : smoke. To be characterized as either positive- or negative- affect smokers, the subjects had to smoke during the appropriate film and indicate a congruent mood on an affect i checklist. The major finding was that 73 percent of the female sample of 15 subjects exhibited solely negative-affect smoking compared to only 36 percent of the sample of 39 males. While 80 percent of the females indicated that they were likely to smoke in positive as well as negative-affect conditions, their behavior did not match the self-report in this experiment. It is difficult to determine if the environment of the experiment altered normal behavior patterns or if perhaps, smokers are not accurate in describing the types of situations In which they smoke. A nationwide household-interview survey conducted in 1964, 1966, and 1970 also suggested that a higher percentage of women than men are negative-affect smokers and that little or no difference exists between men and women in the percentage who are positive-affect smokers (180, 181) (see Table 8). A greater percentage of women current smokers endorsed the statement, "it relaxes me." This supports the hypothesis that reduction of negative affect is a more important factor for women smokers. The statements assessing positive-affect smoking did not show a clear gender difference. In 1964, slightly more men than women endorsed the statement "enjoys it" as a reason for smoking, but in 1966 there was no difference between sexes, and in 1970 slightly more female than male current smokers agreed that "cigarettes are pleasurable" (79.6 percent of women versus 77.0 percent of men). To summarize: smoking affects arousal; it is not known whether women smoke to maintain a given arousal •level, to change that level, or to adjust a physical blood level of nicotine. There are a number of studies which suggest that women use cigarettes more In high-arousal, situations than men do. Studies which combine self-reporting with experimental situations providing a good approximation of natural smoking conditions are needed to shed some light on the validity of evaluations by questionaires alone. SMOKING CESSATION There Is an assumption in the treatment literature that men have greater success than women in quitting smoking. The 352 TIMN 0048566

, , . i t , TABLE 8.-Most frequently endorsed reasons for resuming smoking. Fall 1964 and Spring 1966 household interview survey, responses of current smokers. Q: People give all sorts of reasons for either not bei.ng able to or not wanting to stay off cigarettes. What were your reasons, for going back to cigarettes? (Asked if made a serious attempt to stop smoking.) Current Smokers 1964 1966 ® N °'o Selected total M 705 55.7 772 54.9 F 5`2 50.9 588 57.1 No will power .4 291 23.0 27R 19.8 F 209 19.5 191 18.5 It relaxes me M 212 16.8 181 12.4 F 2A5 22.9 192 18.6 Enjoys tt M 144 11.4 123 9.7 F 102 9.5 90 8.7 . r d• Helps keep weight down M 65 5.1 40 2.8 F 75 7.0 57 5.5 Smoke to be sociable M 98 7.7 43 3.1 F 70 6.5 46 4.5 Note: More than one answer was allowable for each respondent. SOURCE: Adapted from DHEW (1969). 353 . , TIMN 0048567

basis of this assertion lies partially in the demographic analyses of cessation rates and partially in the literature on smoking cessation clinics and experimental programs. This section presents the results of both demographic and experimental analyses of smoking cessation. A critical appraisal is made of the relative success of men and women in giving up , smoking and in remaining ex-smokers. Psychosocial and behavioral factors relating to abstinence and difficulties encountered in quitting are discussed. Finally, recommendations are presented for treatment and future research. ' Demographics The quitting rates of smokers are calculated by dividing the number of former smokers by the number of ever smokers within each relevant demographic category. The statistic s are taken from the 1975 USDHEW survey on Adult Use of Tobacco (182). Former smokers are defined as those who once smoked but no longer do so. The term "former smokers" includes both those who have quit on their own and those who have received outside help. Quitting rates of women lag behind those of men, for each category reviewed. Age The USDHEiV tables divide adult age groups into six categories: ages 21 to 24, 25 to 34, 35 to 44, 45 to 54, 55 to 64, and 65 and over (182). There is a trend toward Increasingly larger percentages of former smokers in each successive age group. For both men and women, however, within each age group, the percentage of smokers who have quit is higher for men than it is for women. For example, in the youngest age category, the percentage of female smokers who have quit is 22.6 percent while that for males is 27.9 percent. For a middle-aged category (45 to 54), the female and male percentages are 32.0 percent and 46.7 percent respectively. In the oldest age group, 51 percent of female ever smokers are former smokers, whereas the percentage is 60 percent for males. Bosse and Rose state that the sex differences in quitting are vanishing at younger ages, but Dicken argues persuasively that the absolute amount of convergence is small, and that men remain substantially more likely to stop smoking than women (121, 146). 354 TIMN 0048568

Education Higher levels of education are associated with higher rates of quitting for both men and women. Among those with a college education or higher, 52.1 percent of the men and 48.1 percent of the women who have ever smoked have quit. For all other levels of education, 40.5 percent of men smok'ers and 31.3 percent of women smokers have given up smoking. Although the discrepancy Is less in the most advanced education category, the percentage of female quitters is smaller at both levels of schooling. ~ i ncome : .r~. :; Higher levels of income are associated in both sexes wiW higher rates of cessation. For those ever smokers with ~.....,,,.,,~w..,,..,,. .. ...... ...... „ ...„.incornes under $10,000, the rates of quitting for men and :; women are 34.7 -percent and 30.3 percent respectively. For _..~.. __ ; those with incomes of $10,000 or above, the rates are 45.7 percent for men and 36.2 percent for women. Quitting rates _ of men exceed those of women for all but one ($5,000 to $7,499) of the seven income levels. t \ Occupation There Is a difference of only 7.6 percentage points between the proportion of male and female quitters in the category of professional, technical, and kindred workers, with the male quitting rate at 49.4 percent and the female quitting rate at 41.8 percent. A dramatic increase In this difference occurs, however, among managers, officials, and proprietors. In this category the quitting rate for men is 47.1 percent and that for women is only 26.5 percent. Among sales and clerical workers, 40.1 percent of the men and 25.8 percent of the women have quit. The quitting rate of housewives is in the mid range of the rates for women in other occupations (33.9 percent). In general, then, women are quitting at lower rates than men across the major demographic categories. Psychology of Changing Smoking Habits A- two-year follow-up of over 500 former smokers identified 355 TIMN 0048569

demographic data showing higher proportions of ex-smokers among males than females (57). Men were significantly more likely than women to remain successful abstainers. Men and women made approximately the same number of attempts to quit, and current smokers made more attempts than former smokers (158). Furthermore, successful quitters have usually made at least one abortive attempt to quit before succeeding. A survey of young women, aged 18 to 35, revealed that light smokers had the greatest success in stopping smoking (203). Those factors which consistently seem to differentiate between those who can quit or reduce intake and those who cannot, are the presence of strong motivation and commitment to change, the use of behavioral techniques, and the availa- bility of social support. Those who successfully quit or reduce smoking use behavioral techniques such as substituting candy and gum for cigarettes, and some form of self- reinforcement of desirable behaviors to maintain abstinence (203, 134). Successful reducers use behavioral techniques more consistently and for a longer period of time than those who • fa,il to reduce smoking (134). Successful quitters experience cravings when they stop, but the use of substitutes seems partially to alleviate these feelings (133). Furthermore, those smokers who do reduce intake . are more motivated and committed to personal change (134), and long- term abstainers have niore confidence in their ability to remain ex-smokers (57). Successful reducers receive more positive reinforcement from others and the best known acquaintances of successful abstainers are former smokers (134, 57). Warnecke, reported female relatives to be the primary role models for women who quit smoking (190). Treatment Studies Most smokers who attempt to quit do, not seek outside help to stop smoking. The population that seeks treatment may be one that experiences severe difficulty in giving up smoking. Thirty-nine treatment studies on smoking have reported suc- cess rates for males and females, and have used the cri- terion of total abstinence, or 90 to 100 percent reduction to define a successful result. The studies reviewed here fall into five categories of treatment: education, physician advice, pharrnacotherapy, psychotherapy, and behavior modification (Tables 9-13). The 356 TIMN o048570

TABLE 9 -Education-Smoking cessatioo treatment results by sex. End-of-Treatment Six Months Long Term °•Study Treatment N 19.) (96) (96) 1. Gudford,1967• • Fiveday Plan' unaided 76M 23M 100F 12F 2 Aided 82M ~ 27 M 91F l 29F 1 2. Peterson et al.,1968• • Fiveday Plan 134 M&F 79 M&F 19M (18 mo. follow-up 19F on 121 Ss) 3 Berglund, 1969• ° Five<day Plan 895 M&F 87M 32M 31M 84f 27F >2 23F>1 (4-18 mo.) w k.n 14 4. Delarue, 1973 Education, small groups 472 M&F 34M (12 mo ) 21F 5. Danaher et al., 19781 Education; skill training group 11F 50 (of 8 Ss finishing 50 (9 mo.1 treatment 6. Ochsner & Damrau. 1970 Pamphlets' 20M 85M 33F 52F >1 7. Pyszka et al., 1973• • American Cancer Society Clinics 131M 39 M&F 28M 223F 20F (18 mo.) 8. Kanzler et al., 1976 Smokenders 210M 70M 343F 69F 30F>f (48 rno.l 9. Dubren, 1977• T.V.spots 92M 15M 218F 7F~- 1 ! 1 p<0.05 'Success = 90-10096 reduction in smokin® "Results based only on those completing treattnent or contacted for follow-up. 20.05 p< 0.10 1Pregnancy intervention study i r }

, TABLE 10 -Physician advice- Smoking cessation treatment results by sex. End-of -Treat ment Six Months I ony Term Study Treatment N /96! (961 W 1. 8urns, 1969 M.D. advice to resp. dis. pts. 66M 28F 63M> 32F 1(3 mo.l 2 Handel. 1973 Anti-smoking message in_ med.exam 45M 55F 38M> 1(12 mo.) 11F 3. 8urnum, 1974 M.D. advice 84M 40W 29M 18F 4. Saric et al., 19761 M.D. advice (spont. quitters) (interventionl (controll 134F; 24 63 47 83 14 14 5. Donovan, 197711 M.D. advice 552F 60% reduction 1 P<0.05 tPregnancy intervention studies

• +. • . ~. r . . . . . . . r - . r . .-. . . .. . . . . . . . ~•1. • . •/ . . •. •-. v . . I'. . . . . . . '.• • ~ . r J ~ • 1. + •~ • M + . . J~ . . . r . . . . . W TABLE 11 -Pharmacoth6rapy-Stnoking cessation treatment results by s®x. Study Treatment N Endol-Treatment o (KI Six Months (96{ Lonll Term (%1 1. Tur1a, 1958• Hydroxyzine 23F 4F 2. Whitehead and D i Methylphenidate 10M 20M OM ~i2 mo 1 av es. 1964 Diazepam OF OF OF 3. Wilhelmsen, 1968 Methylscopolamine 291M 66M> 112mo 1 tranquilizer 200F 41F 4. Wetterqvist, 1971 • Methylscopolamina 192M 60M 1974• 98F 33F ~ 1 12F /12mo.) 6~ 160mo.1 5. Arvidsson, 1971 • Anticho/inergics Groups, 60M 86M 48M aversion therapy SOF 86F 22F ~ 1112mo.1 6. Merry and Preston, Lobeline 45M 29M 1963• 31F 32F 7. Golledge, 1965' Lobelme & placebo 19M 63M 8F 73F 8. Ross, 1967' Lobeline 728M 40M> 1 21M ~ 1(10-57wks.) Amphetamine 745F 29F 12F 9. Schauble et al., Lobe/ine 33M 18M 1967• Amphetamine 35F 26F ~ Lobeline, amphetamine 14M 57M and education 17F 26F 10. West et al., Lobeline, amphetamine 255M 43M\ 22AM 1977• 288F 33F ' 1 13.5F ~ 1 (60 rno.) l p < 0.05 •Resuhs based only on those completing treatment ar contacted lor /ollow•up.

. -4 TABLE 12 .-Psychotherapy -Smoking cessation treatment results by sex. Percent Abstinence End -of -Treatment Six Months Long Term Study Treatmert N (%1 1%) (%) 1. Moses, 1964 Hypnosis, discussion 35M 83M 11M 8M w 15F 53F>2 12F 12F (12 mo.l rn 0 2. Mann and Janis, 1968 Emotional role•playing 26F 23•50F 118 mo.t' 3 Streltzer and Koch, 1968 Emotional role•playing 30F OF 14 wks. post) 4- Lichtenstein et al., 1969 Emotional role-playing 54F 9F (1 •5 wks. post! 5 Fee and Benson. 1971 Group therapy 306M 56M 1 204F 38P 1 9F>1 (6•12 mo.) 6. 8ozzetti, 1972 - Group therapy 7M 57M 85M /12 mo l 7F 43F . 57F 7. Tamerm, 1972 Group therapy 16F 69F 1 p<0.05 '% reductron in smoking 20.05< p<0.1 I

TABLE 13 -8ehavior mod'ufication-Slnokin9 cessation treatment results by tex. P.rcent Abstinence Endof-Treatment Six Months Long Term Study Treatnsent N (%) 1%1 1%1 1. Keutter, 1968 8reath holding, coveranl 73M IBM control, negative practice, attention placebo 73F 29F 2. Suedlek/ and /kard, 1973 Sensory deprivation 3M 10oM 67M (3 moI 2F 60F 6oF 3. l)elahunt and Curran• Negative practice or selt-control 60F 61 22 1976 Nepative practice and sell- 89 66 \ contro I 1 / .. Comrol 16 0 y Nonspecific treatment 66 11 (JI 4. Tongas at at., 1976' Covert sensis., smoke aversion, group therapy, combined treatment 5. Russell, 1970 Electric shock aversion 6. Chapmao et al., 1971 Electric slsock, setl• management: post-treatment therapist monitoring: 2 weeks : I i weeks : 7. Serecr 1972 Etectric shock aversion, imagined vs. real smoking 8. Russell et al., 1976 Electric shock and controls 38M 34F 71M` 39F / 2 62M 32F ~ 2(12 mo.) 18F > 2 1241...1 tOM 70M 4F 5pF 6OF (12 mo.) 4M 76M 25M 25M 8F 100F 37F 29F 112 mo.l 4M l00M 60M 60M 7F 86F 67F 57F 56M •' 32F 28M 64M1 28F 67F1 lp < 0A5 'Results based only on those completing trealment 20,05 c p<0 10 d 'Percent reduction, little for F: more tor M in imagined smoking condition t Two weeks post-,reatment

I categorization is, by necessity, only a rough separation of treatment modalities. Evaluation of the gender difference question, however, does not rest directly on the categorization schema. Many of the studies listed in the tables did not report significance evaluations for male/female quitting rates. Therefore, a chi square statistic or Fisher exact probability test was calculated wherever sufficient data were available. Because of the limited number of studies identified for analysis and the often limited sample size, results of borderline (0.05 < p < 0.10) and acceptable (p < 0.05) levels of significance are reported for the reader's information. The end-of-treatment cessation rates are high for all types of treatment, but the maintenance of cessation tends much lower. In 1971, Hunt,. et al. demonstrated that recidivism curves of heroin, alcohol, and smoking are almost identical, with long-term cessation falling off steeply from the snd of treatment •(91). Within three months, approximately 35 percent of successful quitters are still not smoking, and by one year, the figure is closer to 20 percent. In 1978, another reviewer cited virtually the same figures (140). There have been reports of improvement in techniques for obtaining abstinence and in maintaining it, using rapid smoking (an aversive conditioning technique), hypnosis, and group therapy. The long-term cure rates of 60 percent or higher at six months claimed in some studies have not been reproducible in other settings. The smoking cessation literature has been rebently reviewed in detail (186, 78, 59). Across all treatments, women have more difficulty giving up smoking than men both at the end of treatment and at long-term points of measurement. No studies have been reported in which women do significantly better than men. Several of the larger studies show higher abstinence rates by men, but many show no difference. Results In the tables are based primarily on those who complete treatment programs. Attrition rates are very difficult to evaluate because most studies do not discuss the issue of subjects who drop out of treatment. Because of the emphasis placed on the role of physi- cian advice in increasing smoking education and promoting cessation, an estimate of its effectiveness is relevant. From retrospective data, it is estimated that 35 percent of people who have been advised by a doctor either to quit (170). Twenty-five percent of those who have not talked to a physician about smoking quit, and only 12 percent who have 362 TIMN 0048576

, , . , been told by a physician that it was permissable to continue smoking quit. The prospective treatment literature yields varying estimates of the impact of physician advice. Ten to 25 per- cent of patients advised by a physician to quit or cut down actually do so (186). Gender does not seem to exert a par- ticular influence (55). The primary variables associated with the ability to quit after physician admonition were good psychosocial assets, psychological stability, and the ability to verbalize depression (55). Success in treatment in general seems to relate to personal characteristics. A shorter smoking history and lower cigarette consumption also predict a greater likelihood of cessation (138, 102, 184). In addition, those subjects most likely to succeed in treatment are highly motivated, believe they will succeed, and are confident of their ability to stop smoking (130, 176, 80). One group of women that seems to have great difficulty in giving up smoking in treatment is homemakers. Homemakers in the age range of 18 to 35 tend to be heavy smokers and heavy smoking is one predictor of failure in treatment (203). Kanzler, et al. found that homemakers were less successful at quitting, particularly at long-term follow- up (102). However, as previously discussed, since homemakers have quit rates in the mid-range of those of women in other occupations, therefore the difference may apply only to those homemakers who seek help through treatment programs. Wilhelmsen found significant male/female differences in treatment success rates and stated that the poorer per- formance of women related almost exclusively to the unsuc- cessful results of homemakers (196). These women explained that cigarettes served as companions and they reported the difficulties of being without adult company all day and of being deprived of outside activities as obstacles to giving up smoking. Cigarettes have also been described as a means of temporally partitioning the day, of achieving physical autonomy from children, and of providing role differentiation (72). Frieze, et al. reported women face more life stress than men and have more symptoms of psychological distress (67). Waters reports that women show more overt signs of neuroticism than men (192). Furthermore, he finds an asso- ciation in women between degree of neuroticism and amount smoked. Burns also found that female smokers had higher neuroticism scores than did female nonsmokers. No such dif- ferences were found in men (30). 363 b TIlVIN 0048577

. J : ; : ; r , , been told by a physician that it was permissable to continue smoking quit. The prospective treatment literature yields varying estimates of the impact of physician advice. Ten to 25 per- cent of patients advised by a physician to quit or cut down actually do so (186). Gender does not seem to exert a par- ticular influence (55). The primary variables associated with the ability to quit after physician admonition were good psychosocial assets, psychological stability, and the ability to verbalize depression (55). Success in treatment in general seems to relate to personal characteristics. A shorter smoking history and lower cigarette consumption also predict a greater likelihood of cessation (138, 102, 184). In addition, those subjects most likely to succeed in treatment are highly motivated, believe they will succeed, and are confident of their ability to stop smoking (130, 176, 80). One group of women that seems to have great difficulty in giving up smoking in treatment is homemakers. Homemakers in the age range of 18 to 35 tend to be heavy smokers and heavy smoking is one predictor of failure in treatment (203). Kanzler, et al. found that homemakers were less successful at quitting, particularly at long-term follow- up (102). However, as previously discussed, since homemakers have quit rates in the mid-range of those of women in other occupations, therefore the difference may apply only to those homemakers who seek help through treatment programs. Wilhelmsen found significant male(female differences in treatment success rates and stated that the poorer per- formance of women related almost exclusively to the unsuc- cessful results of homemakers (196). These women explained that cigarettes served as companions and they reported the difficulties of being without adult company all day and of being deprived of outside activities as obstacles to giving up smoking. Cigarettes have also been described as a means of temporally partitioning the day, of achieving physical autonomy from children, and of providing role differentiation (72). Frieze, et al. reported women face more life stress than men and have more symptoms of psychological distress (67). Waters reports that women show more overt signs of neuroticism than men (192). Furthermore, he finds an asso- ciation in women between degree of neuroticism and amount smoked. Burns also found that female smokers had higher neuroticism scores than did female nonsmokers. No such dif- ferences were found in ,ren (30). 363 . , 048518

, ; Some studies have shown that women who smoke are both more subject to psychological stress and more outgoing than women who do not smoke. In a prospective study on women and smoking, Cherry and Kiernan measured personality traits in young women before the onset of smoking (31). They found that smokers had high neuroticism and extroversion scores before taking up the habit. They add that current women smokers are more extroverted and also more neurotic than nonsmokers. There is evidence that women smokers are more independent-minded, assertive, self-opinionated and forthright (143). The later authors report that women.smo- kers are also characterized by apprehension and tension, and that these characteristics are related to an inability to give up smoking. The presence of psychological distress has also been shown to affect the success of women in treatment. Peterson, et al. found that, while 23 percent of the men who had participated in a smoking program cited nervousness as the principal reason for resuming smoking, 43 percent of the women cited this reason (135). Russell reports that the presence of depression was related to dropping out of treat- ment, and that depression was more frequent and severe among the women in his sample (148). In a later study, Russell found that within the treatment group, women had worso psychiatric adjustment scores than did men (140). Furthermore, although the degree of psychiatric adjustment did not differ between male treatment successes or failures, treatment successes among women were significantly more likely to have good adjustment scores. Rode found that suc- cess in a smoking withdrawal program was related to lack of tension and apprehension for women (144). That smoking might indeed act as a method of coping with psychological and social stress is illustrated by the fear reported by many women that they will engage in symptom substitution-- specifically overeating--if they stop smoking (30, 125, 4). It Is also possible that underlying stress in women impedes the strength of the determination required to cease such behaviors as smoking and overeating. Weight gain is a fre- quently reported consequence of giving up smoking (144). The Smoking Withdrawal Syndrome Few of the studies reviewed here mentioned gender as a factor in connection with withdrawal symptoms, and none 364 TIMN 0048579

. suggested that men and women differ in the severity of ~ smoking withdrawal symptoms. However, Shiffman analyzed ° Guilford's raw data, and staged that 15 of the 18 major ' symptoms reported by subjects demonstrate sax differences ` (164, 80). Thirteen of those 15 symptoms were more fre- quently reported by women. Other studies show similar, > although not statistically significant, trends (179, 135, 202). ~ Factors contributing to relapse, such as craving and , nervousness, were reported to be similar for men and women (179). Women who experienced the greatest craving during : the Initial five days of abstinence were most likely to r relapse (80). Since women score higher than men on measures of anxiety as a general rule, it is possib le that they would be more susceptible to relapse if smoking had been their customary means of reducing such dysphoria (164). Women may also pay more attention to somatic symptoms than men, as they make more frequent use of all health care ser- vices, specifically for headache and weight gain (110). It is likely that the abstinence syndrome is a major° factor in recidivism during the first few weeks of cessation when relapse Is most common and that the number of cigarettes smoked per day is an important variable in determining the severity of the withdrawal (91). The issue of a gender difference in withdrawal severity is a• major area where research is needed. Treatment Recommendations Perri, et al. recommend that smoking cessation programs with a behavioral emphasis be comprehensive, multifaceted, long- term, and that they include self-reinforcement and problem- solving procedures (134). Given the difficulty for some women in simultaneously dieting and attempting to quite smoking, smoking withdrawal programs should adopt a total approach to health including advice on dieting, exercise and the immediate benefits of abstinence (144). Marlatt and Gordon write that relapse potential is greater for individua'ls whose daily schedule fails to include some rewarding or pleasurable activity (114). It would appear useful to attend to this issue in smoking treatment programs. A social support hypothesis is frequently cited in the treatment literature to explain gender differences in quitting. It is often suggested that women do better than men in 365 , _ --- ' TIMN 0048580

programs which provide a maximum amount of social support, and tend to do worse in situations where program support is low or outside factors militate against quitting. For example, Resnikoff, et al. were able to differentiate between those women (but not men) who did poorly in group-plus-medication treatment and those who did weli using the Social Introversion Scale of the Minnesota Multiphasic Personality Inventory (142). This scale measures the degree of discomfort in social situations and the presence of outgoing tendencies. Women scoring high on this scale (shyer, more socially introverted) were less likely to quit than low-scoring women. This study provides just one example of the observation that social support seems to be of lesser consequence to men in quitting smoking, although spousal support is important (160). As the overall categories in Tables 9-13 show, women do more poorly in treatments characterized by less individual attention, such as education and pharmacotherapy, compared with the categories of psychotherapy and behavior modification, where contact is usually maximized in a small group or in an individual-to-therapist setting. Dubren reports that twice as many women as men par- ticipated in a television stop smoking campaign, but that fewer women stopped smoking--presumably because of a lack of support (54). Guilford found that when men and women participated in group programs, success and failure rates were the same for both sexes (80). When they did not attend group programs, men maintained the same sucqe.ss and failure rates, but women achieved markedly lower rates. There is also support for the notion -that groups are particularly effective for women if they are sexually homogeneous (80, 45). Tamerin writes that the group . can provide support, empathy, and shared identification with others going through a similar process (176). The group also provides an avenue for affective expression, so that the relevance of cigarettes to psychosocial events and the personal meaning of giving them up can be discussed. Given the differential reaction of men and women to quitting smoking, as well as the traditionally greater willingness of women to discuss affective issues, it is not surprising that all-female smoking-cessation groups have been particularly attractive. Marlatt and Gordon studied the circumstances under which smoking relapse Is most likely to occur (114). They claim that experiencing stress in the form of a negative emotional state, social pressure, or interpersonal conflict is likely to lead to smoking among those who are attempting to 366 TIMN 0048581

abstain. The occurrence of a full-blown relapse, however, can be attributed to the cognitive reaction to stress-induced smoking. Many individuals who are trying to abstain, view a single slip as evidence that they have failed, rather than as a natural and predictable reaction to a stressful situation. Marlatt and Gordon advocate teaching those who are trying to quit the importance of not viewing relapse in an all-or-none manner. Rather, they suggest teaching smokers to "plan for a relapse," to become psychologically prepared to accept a slip as a natural part of the difficult process of quitting. Another factor that appears to influence the success of women in treatment programs is the smoking of significant others in their environment. Kanzler, found a significant trend for women to give up smoking If no one in their daily environment was a regular smoker (102). This trend was only slight for men, although spousal encouragement' was related to success in one large study of smoking cessation treatment in men (160). Berglund, West, and Warnecke also emphasize the influence of the smoking behavior of significant others in female attempts to quit (4, 194, 190). Sensitizing friends and relatives who are smokers to this problem and advising discretion in smoking behavior on their part, m ight increase treatment effectiveness for women. Conclusions Treatment programs should specifically deal with means of handling anxiety and tension, ways to combat weight gain, and prepare smokers for mini-relapses. Social support should be maximized. It may be increased through choice of treatment modality networks of "buddies," friends and relatives, and the involvement of spouses. It should be possible to capitalize on the heavy com- mitment of women to the health care system, both in terms of their own use and their role as family providers. Health professionals need to devise targeted interventions for women with this in mind. DISSEMINATION OF INFORMATION ABOUT SMOKING Health Attitudes and Behaviors The extraordinarily serious health consequences of smoking have not deterred almost 30 percent of the adult female and 367 i TIMN 0048582

40 percent of the adult male population from smoking regu- larly. Seventy to 80 percent of these smokers agree that cigarette smoking is harmful, is a health hazard that requires action, and causes disease and death (182). Former smokers and nonsmokers take a much stronger stand on these three points, ranging from 87 to 96 percent agreement. Gender differences are very slight. The value placed on health compared to other positive life goals was slightly lower for smokers than nonsmokers, and highest for ex-smokars (197). Out of a maximum factor score of six, current smokers averaged 4.66 (M = 4.55, F = 4.81), and nonsmokers averaged 4.82 (M = 4.68, F = 4.9) and ex-smokers averaged 4.89 (M = 4.78, F= 5.06). The higher scores of women support their traditional concern with health in our culture but they are incongruent with recent smoking trends (110). Fewer current smokers than nonsmokers and ex-smokers report having personally known someone with coronary heart disease, lung cancer or emphysema/chronic bronchitis. This finding may be attributable to a process of denial. Only about one-third of current smokers admitted knowing someone personally whose "health" was adversely affected by smoking while over 60 percent of nonsmokers knew such a person. Clearly, mechanisms must be operating in smokers to reduce cognitive dissonance caused by their behavior and their knowledge of the health consequences of their behavior. One of these mechanisms may be to deny that the health problems of others are connected -to smoking. Women in our society are. more involved with health care services (110). They arrange for health care services and act as role-models for children. Sources of Information - - There are a variety of ways that people can learn about the health consequences of tobacco use. The information gathered from and effects of tobacco company advertising will be discussed separately below. The major sources of information fall into a number of categories. Health Care Providers. The influence of physicians and nurses as communicators of information and as exemplars of healthy life styles has been the subject of much research (186). The greater' concern about health among women and their greater 368 TIMN 0048583

contact with health professionals, provides an obvious avenue of intervention(110). i~ealth professionals should be continuously reminded of their potential impact and advised to use it to influence women to reduce smoking. Physicians are considered the most authoritative source; with the greatest potential for influencing patient behavior. From the self-report of adults, physicians are not delivering enough anti-smoking Information and advice. In 1975, a full 64.6 percent of male and 60.8 percent of female current smokers claimed that they had never received advice from any doctor about quitting, cutting down, or continuing smoking (182). About 19 percent of male and 21 percent of current female smokers had been advised to quit. Combining advice to quit and/or cut down, the percentages rose to 34.8 percent of men and 37.7 percent of women. In 1970; the percentages of men and women who reported such advice were 30.2 percent and 34 percent, respectively (181). A somewhat lower estimate of physician advice was obtained from an ongoing nationwide study involving approximately 8,000 people (175). Advice to quit or cut down was reported by 22.4 percent of the subjects, and lack of advice by 77.6 percent; there were no significant gender differences. A survey of physicians' opinions about smoking and health in the mid-1960s revealed that 38 percent claimed they advised "all" or "almost ailp (95 to 100 percent) of their patients who did not have smoking-related disorders to quit or cut down (74). Eighty-eight percent of physicians claimed they gave such advice to patients with lung and pulmonary conditions. Nurses spend more time in direct patient contact than do physicians and can exert a major role in delivering information as well as serving as exemplars. Most nurses are aware of this responsibility (73, 61, 129, 183). Only 10 percent of nurses claimed to discuss smoking and health with "almost all" or "most" (65 to 99 percent) of their patients or students (129). Another 21.5 percent claimed to have discussed it with 35 to 64 percent of patients or students. Only 50 percent of current smokers, compared to 65 percent each of former smokers and nonsmokers, suggested stopping to 5 percent or more of their patients and students. While the identical question was not asked of nurses in the 1975 survey, a number of valuable questions relating to exemplar status were posed (184). In almost every case, current smokers took the weakest position on exemplar role, former smokers were in between, and nonsmokers were 369 - : TIMN 0048584

I strongest. For all questions, the proportion of nurses who agreed "strongly" or "somewhat" with the statements of exemplar role is reported here. Regarding their own behavior, 69.5, 91.7, and 94.5 percent of current, former and nonsmoking nurses respectively felt that they should set a good example by not smoking. This percentage varied according to work location. Lowest percentages were given for hospital duty (70.0, 83.3, and 89.2 percent for current, former and nonsmokers respectively), intermediate for private physician's office (79.9, 86.7, and 90.5 percent, respectively), and highest for private duty (91.1, 91.4, and 94.4 percent, respectively). A much lower rate of agreement about not smoking in public while in uniform was obtained; only 44.4 percent of current smokers, 67.1 percent of former smokers, and 72..8_ percent of nonsmoking nurses concurred. Nurses believe that it is their responsibility to convince people to stop smoking; (64 percent of smokers, 74 percent of former smokers, and 64.8 percent of nonsmokers). Approximately 54 percent of smokers, 81.3 percent of former smokers, and 82 percent of nonsmokers said they had tried to persuade someone other than patients to quit, and a much higher percentage reported convincing someone not to start (83.4, 78.6, and 75.8 percent, respectively). Finally, 52.1, 78.2, and 85.4 percent of the respective groups agreed strongly or somewhat that nurses should be more active in speaking to lay groups. Given the possible role modeling effect of female nur- ses, a need exists for adequate preparation of all health professionals In smoking and health counseling. This pre- paration should include education on the health hazards of smoking as. well as effective methods of counseling patients. There is little information available about the role played by other health care providers in dissemination of information or discouragement of smoking behavior. Nation- wide campaigns are currently being aimed at physicians and dentists to increase their commitment to and involvement with this task. Other health care providers should be encouraged to take a more active role and adopt exemplar status as well. Educators. Adult educators include those in schools and colleges, job training, community organizations (churches and other religious groups, Young Women's Christian Associations, and Red Cross, civic organizations, social service groups, cultural groups) and in school-based programs for parents: 370 TIMN 0048585

; There are a large number of sources of information about smoking available from educators in adult settings and in programs for parents. These have been studied in-depth and reviewed elsewhere (186, 178) The frequent contact with and involvement of women in the school system should provide excellent opportunities to provide female-oriented information. Peer group. This group is an important, influential source of information on behavior. Evidence is strongest for the effect on initiation (addressed earlier in this Part). In two studies of British working class women, the peer group was an Important source of information about smoking pregnancy (112, 72). Other strong relationships within the. lay adult community have also been reported (113, 190). Famil . Significant others, especially within the family, have been shown to be primary sources of information to pregnant women (112, 72). The female relative may serve as a particularly important role model for black women (180). Media: Television, Radio, Film, Newspapers, Magazines. The use of the mass media as a source of information as wel i as . a tool in effecting cessation has been extensively developed in . recent years (1979a; 186, 178, 181, 191, 56). Since women are almost exclusively the target audience of women's service magazines, effort should be devoted to : using this medium to provide information on smoking and ; health, cessation techniques, and clinic availability. These magazines have not adequately disseminated information on ; smoking and health (169). : One of the,principal reasons suggested for this failure : is the power that tobacco companies wield through the economic incentive 'of advertising (169). Only one women's service magazine aoes not accept cigarette advertising in the United States. Frank admission of the economic dependency upon such advertising has been made. Not a single leading national woman's magazine that accepts cigarette advertising in seven years of publication printed an article "...that would have given readers any clear notion of the nature and extent of the medical and social havoc being wreaked by the cigarette-smoking habit" (169). Smith goes on to point out that those magazines that do ;not accept cigarette advertising, or have no advertising at all, have done considerably better at informing their readers of the health risks of smoking. i 371 TIMN 0048586

I , Advertising. In recent years, advertising in the United States has been directed specifically towards the women's market, with themes as diverse as the emancipation of women, the first woman (biblical reference), romantic love, and the independent single woman. Most girl smokers have a positive impression of the individuals pictured in cigarette adver- tisements. The latter are seen as attractive (by 69 percent), enjoying themseives (by 66 percent), well dressed (by 66 percent), sexy (.by 54 percent), young (by 50 percent), and healthy (by 49 percent). There is no comparable data on how girl nonsmokers or young adult women view advertising. Thus, advertisers have been successful in creating a sense of mystery, sophistication, and power around the beha- vior of smoking. Although smoking was once frowned upon for women, people now respond less negatively to a woman smoking (16). There is evidence that, for some women, smoking is linked with attitudes and behaviors that comprise a sociaily valued and successful self-image, and that giving up smoking is a threat to that image (116). A majority of former and nonsmokers of both sexes In the 1975 Adult Use of Tobacco Survey (182) agreed with the statement, "Cigarette advertising should be stopped completely." The percentages for men were 56.9 percent for nonsmokers and 56.4 percent for former smokers, and for women, 68.2 percent for nonsmokers, and 62.5 percent for former smokers. , However, only 42.6 percent of male smokers and 42.5 percent of females smokers agreed with the state- ment. It appears that adult smokers value cigarette adver- tisements, but why they do--whether for information about brand characterization and availability, Identification with the image portrayed, or some other reason--is not known. Fishbein concluded that cigarette advertising influences the decision ' to smoke as welt as the choice of brand. Furthermore, he points out that cigarette advertising may serve as a discriminative stimulus for smoking behavior. Advertising can influence the initiation of smoking, the choice of brands smoked, and the level of consumption. Commenting that the tobacco Industry asserts that advertising serves only to influence brand choice and not initiation or consumption, Fishbein maintains that it is somewhat unrealistic to assume that an advertisement which can do one of these things is not also capable of doing the other. While additional research on the effects of cigarette advertising is clearly necessary, this review suggests that cigarette advertising does affect cigarette consumption (63). 372 TIMN 0048587 ,

. ; . Restrictions have now been placed on advertising in many countries in the world, including the United States. There is no uniform agreement that the ban on televised cigarette advertising in the United States and the United Kingdom significantly reduced consumption. However, it is generally believed that each action of this sort--including the U.S. Surgeon General's Reports and the Reports of the Royal College of Physicians, Taxation, and Legislation--has a cumulative effect on per capita consumption (191, 8, 136). The Failure to Disseminate Information. Many of the critical_ evaluations of public health campaigns conveying anti-smoking information maintain that little attitudinal or behavioral change is ever affected (178). Fishbein (63) argues that there is Insufficient information describing the complex relationships between cigarette smoking behavior and beliefs, attitudes, and intentions to make this conclusion. He further maintains that it is ne$essary to know to what extent decisions regarding initiation, reduction, increase or cessation are under attitudinal (individual, personal) or normative (society-influenced) control. • The importance of personalizing the health message, and the failure of the public to personalize the health messages that they have received is emphasized. For example over 80 percent of the smokers agree with the statement that smoking is hazardous to health but on the question, "Are you in any way concerned about the possible effects of cigarette smoking on your health?" only 25 percent of current smokers, stated that they were "very concerned," another 22.6 percent were "fairiy concerned," 18.9 percent were "only slightly concerned," and a final 31..9 percent were "not concerned" (197). Fishbein maintains that the public is not effectively informed about the general danger to health posed by smoking and is even less informed about the connection with specific diseases. He concludes that the content of an effective message is fourfold: that continued smoking leads to negative outcomes; that stopping smoking leads to positive outcomes; that personal relevance must be established; and that normative infiuences must be appealed to by maintaining that significant others think an individual should quit. Smoking and Weight Control. Women who smoke are, on the average, thinner than women who do not smoke. The reported mean weight difference ranges from 1.2 to 4.5 pounds (7, 17, 373 TIMN 0048588

90). Weight gain has been a frequently documented con- sequence of quitting smoking, both in males and females (135, 196, 37, 65, 70, 202, 179, 17.) Studies of males have reported weight gains among former smokers which range from 1 to 12 pounds greater than those who continue to smoke. In one such study, the authors observed that, while 60 percent of continuing smokers gained weight, among quitting smokers the observed proportion was 85 percent. These figures gave rise to an observed-to-expected ratio of 1.4, suggesting that those who quit are 40 percent more likely to gain weight than those who continue to smoke, but a significant proportion of observed weight gain among men who quit smoking would have occurred even if they had continued to smoke. The single major report on lifetime smoking and weight patterns in women examined data provided by approximately 57,000 female members of a national weight-reduction program (17). Cross-sectional analysis indicated that current smokers weighed less than nonsmokers by 1.2 pounds and 4.0 pounds less than former smokers. Inhalers were significantly less obese by 5.7 pounds than current smokers who did not inhale. A 40-year longitudinal analysis of weight in relation to reported lifetime smoking history revealed that between ages 30 and 50 (the two decades after the majority of those who quit had discontinued smoking), the former smokers gained more weight than continuing smokers, both for inhalers and non-inhalers. The calculated weight gain after cessation varied substantially by amount smoked; heavy smokers who inhaled (>41 cigarettes) gained 30 lbs., while light smokers who inhaled (1 to 10 cigarettes) gained only 4 pounds. The observed differences in weight persisted through age 60. Conclusions of this study may not, in fact, be directly applicable to the total female population. This study raises the issues of reporting and recall bias among this obese population (mean group weights ranging from approximately 171 to 180 pounds), as well as self-selection into continuing or former smokers. The implications of such studies are important. The image of the slender, attractive female pervades our culture and is certainly present in tobacco advertising (Hall and Havassy, in press). Do women perceive weight gain as a significant and unavoidable sequel to discontinuing smoking? There is evidence suggesting that fear of weight gain may keep women from quitting smoking. Women are more 374 - TIMN 0048589

. , concerned with weight than men are. In the 1975 NCHS survey, the percentages of female and male smokers who responded "strongly agree" or "mildly agree" to the statement, "8eing afraid of gaining a lot of weight keeps people from quitting cigarettes" are shown in Table 14. Attempts have been made to examine the cause of such reported weight gains. The mechanism of weight gain with cessation of smoking has not, however, been elucidated. Trahair and others have reported that appetite increased with smoking cessation, and the resulting increased caloric intake-_.-. caused weight gain. Other studies have suggested that smoking may, in fact, directly affect metabolism. Glauser, et al. studied seven males before and one' month after cessation. 8ody weight and surface area increased, while heart rate, serum calcium, sugar, and oxygen consumption decreased. Conversely, however, Sims observed no change in resting metabolic rate, thermic response to exercise or meals, and no change in serum T3 or T3 (166). Further research is necessary to define the degree of weight gain after cessation of smoking, the mechanisms by which it occurs and the ability to modify it by educational or behavioral interventions during and after cessation attempts. Stress at Work , A general model of stress at work (38) is worthy of con- sideration. Examination of the sources of stress at work (Fig. 2) reveals a number of Items which are especially salient for women. Discrimination against women in employment, role conflict, authority problems, inequity in promotions, exclusion from decision-making processes and the "old boys" network have been frequently discussed (67). Individual characteristics may be considered from a gender viewpoint as well; for example, some types of psychological disorders, such as anxiety and depression, are more prevalent among women than men (50, 67). The Type A behavior pattern, which is associated with male cardiovascular disease, has been shown to be unrelated to sex once socioeconomic status is taken into consideration (163). An additional set of stressors originates in the extraorganizational environment. A prospective study of the relationship of employment status and employment-related behaviors to coronary heart disease (CHD) incidence was con- ducted by Haynes and FeInleib (197). Working women scored ~ 375. TIM 0048590

FIGURE 2.- A model of atress at work SOURCES OF STRESS AT WORK Poor phys ca working conditions Work overload Time Pressures Physical danger, etc. an ~n o e am l u~t gy Role conlUct • Responsibility for people • Conflicts reorgamzational boundaries (internal and external), etc ~erpr on~(' Underpromolion' Lack ol job security • Thwarted ambilion, etc. • ~i~~ ' at Work: Poor relations wi oss, subordinates, or colleagues Difficulties in delegating responsibility, elc. * Or ani lional Structure and Climal : i e or no par ic pa lon in decision-making • Restrictions on behavior (budgets, etc.) Office politics • Lack ol effective consultation, etc. • INDIVIDUAL SYMPTOMS OF OCCUPATIONAL DISEASE CHARACTERISTICS ILL HEALTH The Individual: Diastolic Blood Pressure Coronary heart Level of Anxiety' disease Cholesterol level I I Heart rate Level of neurolicism • Smoking • Depressive mood • Escapist drinking Tolerance for ambiguity Job dissatisfaction Reduced aspiration, etc. • Menial ill Type A health behavioral pattern I Ex1ra Or4aNz~ional ources o ress: Family problems • Life crises • Financial dilliculties, etc.' Source: Adaped from Cooper and Marshall (1976). • Items marked by asterisk (•) are particularly relevant to female workers.

TABLE 14.-Percent Affirmative Responses TO STATEMENT "Being Afraid of gaining a lot of weight keeps people from quitting cigarettes" SNKMCiNG STATUS VDMEN (%) MEN (94) Never Smoked 59.0 51.5 Formerly Smoked 63.1 53.6 Currentiy Smoked 59.9 47.3 Cite - National Center for Health Statistics, 1975 377 TIMN 0048592

higher on scales measuring daily stress, marital dissatis- faction, and aging worries, than men. They were also less likely to display overt anger than either homemakers or men (87). tiVhile Incidence rates of coronary heart disease in working women were not significantly higher than in homemak- ers, an excess risk of CHD was identified among women who were employed in clerical jobs and had children. The risk factors for CHD in this group included family responsibilities, suppressed hostility, a nonsupportive supervisor, and low job mobility over the preceding ten-year period. Smoking Habits of Health Professionals There are relatively few studies available which present gender-specific smoking rates in various professions. Health professionals were selected for analysis because they were more likely to be aware of the health consequences of smoking than the general public; this group has also been studied more extensively. Physicians~ The smoking habits of male and female physicians In five nations are presented in Tabia 15. Smoking rates in the general population are provided for comparison when supplied by the authors. No breakdowns by gender are available for the United States. 5eparate estimates of smoking rate In a small group of women physicians age 36 to 46 at the time, . of survey (195) and in a large sample of predominantly male (93 percent) physicians (183) are listed in the table. In addition, the wives of 3,990 physicians were queried about their own smoking habits and those of their husbands; no information is provided on the occupation of these women (75). Examination of the table shows that smoking rates of physicians, both male and female, tend to be much lower than general population rates. The only exception is the higher rate of current smokers among female physicians in Finland (189). The percentage of current smokers among the sample of U.S. female physicians is higher than that reported in other countries and approaches the rates in the general population. Prevalence of smoking has a strong relation to demographic variables such as profession, income, and educa- tion. We would expect physicians to be in the highest cate- gory on each of these variables and, therefore, to have lower prevalence rates. 378 TIMN 0048593

. . . • r • . •-. . . . . r r . -.. . . . • r. • . - . -. .. . . . . ~ . . . . I 1 TABLE 15 Smoking habits of male and female physicians in selected countries. Percent Smokers Pop. Pop. Pop. Author Country N Never Est. Currant Est. Former Est. 1. Bourke. 1972 Ireland M F 1359 221 17.9 61.6 19.7• 53.9 48.6 26.7 67.6' 38.6• 33.6 22.2 12.7• 7.6' 2. Vuon et al., 1971 Finland M F 843 38 66 34 26 60 20 27 8 3. Wdhelmsen & Faith-Ell, 1974 Sweden l 33 54 38 27 29 19 4. Aaro et al., 1977 Norway M F 740 398 35.3 21.7 53• 36• 371 381 271A 201' 5. Westling•Wikstrand et al., 1970 USA F 81 42 35.8 13.6 6 Greenwald et al.,19712 USA M F 3990 3990 323 363 24 36 433 273 7. USOHEW, 1976b USA M 36574 21 39 641 431 341 'SigniNcant dilference between percentages paired by (•1. 1Stopping rate = former smoker ever smoker 2Sample consisted ol physicians and their wives whose profession was unde/ined. 3Percentages estimated from graph, not specified in text. 4Approximate total of M&F, estimated to be 93% male.

According to the three studies providing comparative data, both female and male physicians are quitting at rates higher than the general population. The percentage of former smokers among female physicians, and estimates of quit rate, are lower than among male physic ians in al l but one of the studies listed. This trend may represent a time lag -in the smoking behavior of women as compared to that of men, or there may be a lower quit rate among women physicians. In two studies, female physicians smoked more cigarettes per day than women in the general population In contrast, wives of physicians smoked fewer cigarettes on the zverage-than their husbands (75). A greater percentage of the wives of physicians than physicians themselves, were smokers in every age group except the oldest. The percentage of current smokers appeared to be inversely related to age in the group of wives, but virtually stable across age for the physieian-husbands. Husbands and wives tended to have similar smoking habits. Based on a small sample of women graduates of a single U.S. medical school, Westling-Wikstrand, et al. (195) reported that 58.8 percent of the current smokers belonged to the category "professor," (academic appointment of assistant professor or above, with or without board attainment) when ranked on professional attainment. The other categories were "boards" (specialty board certification but not professional appointments), "no boards" (in practice without board certification or professional appointment), and "not in practice." The "professor" group was characterized by greater likelihood of being single and having fewer "habits of nervous tension." Compared to other groups, this group had the lowest depression scores, average anger scores, and the highest anxiety scores. ' The authors comment that this group of women was the most similar to their male colleagues. They may also have experienced fewer problems with ambivalence about sex roles, self-image, or conflict over aggressive behavioral patterns. The presence of the, high anxiety scale, however, casts some doubt on this general ization. Women in U.S. medical schools are subjected to significant psychological pressures and often experience emotional problems and lack of confidence about achieving the goal of graduation (195). Female physicians also experience significant role conflict (19). The relevance of indices of stress to smoking patterns is again one of inference. If smoking serves as a coping 380 048595

mechanism--a means of reducing negative affect--then it is understandable that female physicians, or any other professional with elevated stress levels, would have higher current smoking rates than the general populace. It is also understandable that they might experience more difficulty in quitting . Psychoiogists. A survey of psychologists in California state universities and colleges found that women psychologists were much more likely to smoke than their male colleagues (47). The rate of smoking was, siightly higher than in male health professionals, and approximately the same for women psychologists (38 percent) and nurses (183) (see Table 16). This smoking rate is significantly above the rate among professional women in general (25.6 percent) and was due to lower cessation rates among women psychologists rather than higher Initiation rates. The most common reasons given for smoking are the stress of work or school, and personal stress. Frieze, et al. state that professional women have to exhibit "male-liken characteristics in order to survive in their jobs, but that these characteristics are often met with criticism and hostility (67). Thus, social and occupational demands are at odds with each other. Furthermore, there Is evidence that female psychologists face very real sex discrimination In the evaluation of their work. Dicken and Bryson (47) report a high degree of power fantasies among women psychologists who smoke. This sup- ports Fisher's finding that women smokers in general seem preoccupied with the issue of power (64). He speculates that cigarettes are used defensiveiy against feelings of powerlessness, weakness, and inferiority. Elevated suicide rates are another correlate to the evidence of excessive stress and difficulty in coping experienced by some female professionals. These higher rates, compared with the general female population, have been observed among women psychologists, chemists, and physicians (118, 173). Factors such as ambivalence about success, role conflict and marginality were offered as dynamics. However, it is not possible to determine whether these higher suicide rates are- due to the self-selection of suicide-prone women into these and possibly other professions, or to the difficulties encountered in professional training and practice (or to an interaction of both). Nurses. A number of studies have shown a higher rate of smoking among nurses than in the general female population in 381 , TIMN 0048596

TABLE 16.-Percentages of cigarette smokers (S), former smokers (FS), and ever smokers (ES) and cessation ratio (FS/ES) among psychologists nurses and other selected health professionals Sample N S FS ES FS/ES Male and predominantly mate samples CSUC male psycnowgists 258 28 35 62 55 Eminent experimental psychologists •909b male ILawton & Goldman, 1961) 72 53 11 64 17 Psychiatrrsts -9b male not reported (Tamenn & Eisinger, 1972) 309 42 21 69 39 American Public Health Association male members tEyres, 19731 3,569 21 40 61 66 Physicaans-93% male (USPHS, 19771 3,657 21 42 63 67 U S. adult males IUSDHEW, 1976a) 5,702 39 29 69 42 Female and predomtnantly /emale samples CSUC female psycholog4sts 86 38 19 57 33 American Public Health Associauon female members iEyres. 19731 1.973 31 31 62 50 Nurses -98% female (USPHS, 1977) 2,429 39 22 61 36 U S. adult females IUSOHEW. 1976a) 6.327 29 14 43 33 Note. CSUC = Cahfornia State Untversity and Colleyes. SOURCE: (47).

, . r the United States. The most recent assessment of nurses' smoking behavior was conducted in 1975 (182, 188). in Table 6, smoking habits of nurses are compared with those of adult U.S. women and other groups of health professionals. Between 1969 and 1975, the proportion of nurses who were current smokers rose. from 37 to 39 percent. Every other category of health professional (physician, dentist, and pharmacist), had substantially reduced smoking rates. The membership of these three professions is predominantly male and current smoking rates vary from 21 to 28 percent. If one examines quit rates in 1975 among the four categori-as of health professionals, It is clear that the majority of physicians, dentists, and pharmacists who ever smoked cigarettes have quit: 64, 61, and 65 percent respectivel.y. Among nurses, only 36 percent have quit, which does, however, compare favorably with adult women (34 percent) and working women (30 percent) (183). Noll surveyed smoking behaviors of nurses by work setting (see Table 17) (129). The overall percentage of current smokers in this survey was, 37 percent, compared to a national average (for 1966) of 33.7 percent in women. There was a smaller percentage of never smokers (41.3 percent) among nurses in that survey than among the female population (56.8 percent), suggesting a higher quitting rate at that time as well. From Table 17 it appears that there is no selective recruitment into the various nursing specialities; the proportion of never smokers is fairly equal across work settings. Differences do appear, however, in the proportion of current smokers according to work setting. Highest rates of smoking are found in psychiatric and pediatric settings, and lowest rates in the four categories connected to education and community involvement: nursing education, working in the community, elementary or high school nursing, and working in a doctor's office. In Great Britain, only 26 percent of maternity nurses smoked regularly, compared to 37 percent of those in general nursing (103). In the United Kingdgm, approximately the same proportion of nurses smoke as women in the general population 44 percent (103, 146). Elkind reports differences in smoking among different types of ward nursing staff. Trained nurses had 41 percent current smokers, learners had 28 percent, nursery nurses had 14 percent, and auxiliaries had 61 percent current smokers. Lampman reported a similar excess of smokers among nurses aides (95.2 percent female) in a large metropolitan 383 TIMN 0048598

TABLE 17.-Cigarette smoking status by work setting for Nurses. CiRarette Smokinrz Status Total• Work Setting Current Former Never Percent N Surgical Units 41.2 19.4 39.4 100.0 529 Medical Units 37.8 18.2 43.9 99.9 476 Operating, Labor, Delivery Emergency Room 39.8 15.2 45.0 100.0 48S Maternity Unit 36.2 17.2 46.6 100.0 197 Pediatrics Unit or Setting 46.6 8.8 44.6 100.0 80 Psychiatric Unit or Setting 49.9 18.2 32.0 100.1 135 Nursing Education Setting 24.6 26.3 48.7 100.1 90 In the Comnunity 26.1 33.4 40.6 100.1 264 Elementary or Migh School 27.3 36.4 36.1 100.0 217 Doctor's Office 24.2 33.8 41.9 99.9 338 Out-Patient Clinic 42.5 15.1 42.5 100.1 113 Other and Mixed 41.3 18.4 40.3 100.0 1,078 •Total N a 6,012 SOURCE: Noil, 1969 384 TIMN 0048599

: ; I ; hospital in the United States (106). Fifty-two percent of that group smoked, compared with 36 percent of the medical nurses (99.3 percent female) and 40 percent of the student nurses (95.6 percent female). This survey was aimed at identifying smoking within the hospital. Thus, true prevalence in this sample can only be higher. Compared to other female health' professionals (see Table 16) in the United States, nurses' quit rates are above some (psychologists, U.S. adult women) and below others (American Public Health Association female members). Knopf Elkind points out that In the British population other female- dominated professional, such as primary school teachers, health visitors and domiciliary midwives, have a noticeably lower rate of smoking than hospital nurses and that nurses- smoke more than other professionals in the U.S. population (103, 186). Entry into the profession of nursing is associated with taking up daily smoking but the degree of occupational stress in a population of 300 British student nurses was not different for smokers and nonsmokers (88). This finding does not rule out the use of smoking as a stress-reduction mechanism, however. Other factors which might contribute to a high smoking rate among nurses are work overload and frustration in professional relationships with physicians. Knowledge of health consequences of smoking is high among nurses, but It has been shown that student nurses are less well-informed than medical students (146). Nurses who quit smoking do cite protection of future health as a major reason (88, 73). Nurses who smoke are less likely than nonsmokers to agree that not smoking is a preventive measure against cancer (103). Similar refusal to acknowledge health risks of smoking is found among smokers in the general popu- lation (18Z). Whether this represents a real lack of knowledge or a method of reducing cognitive dissonance through denial is unknown. The problem Is particularly cri- tical for nurses (and other health professionals) since they serve both as exemplars and as providers of infoormation (103). THE PREGNANT SMOKER--A SPECIAL TARGET The pregnant woman is in a unique life situation. Every substance she ingests and every behavior that she manifests can affect the present and future health status of the unborn 385 TIM.N 0048600

fetus she is carrying. If she smokes, the nicotine, carbon monoxide, and cyanide (and thiocyanate) which she inhales all cross „the,,,.plaeental barrier and enter the bloodstream of the fetus. The risk factors for both mother and fetus have been extensively reviewed elsewhere in this volume as well as in previous reports from the Office of the Surgeon General (see Pregnancy and Infant Health, Part Il of this Report) (186). It is estimated that between one-quarter and one-third of pregnant smokers quit smoking for the duration of pregnancy and that another third cut down. This section reviews the current literature on sources of information available to the pregnant smoker, summarizes available data on prevalence of current smoking and smoking .. . .. . . cessation during pregnancy, and discusses the problem of cessation from a behavioral viewpoint. Sources of Information The same classes of information discussed in the previous section are available to the pregnant smoker. How the pregnant smoker uses these sources and her degree of con- fidence in the information provided seems to be a function of socioeconomie status and parity. Information is distributed through health professionals (primarily physicians and nurses), peers and family, community resources, and the media. Women in lower socioeconomic classes tend to rely ... ... . .. ... . more on lay referral ~systems, such as peers and family, than upon mass media or medical sources (76, 11). Personal transmission of information seems to be more highly valued and readily adhered to (70). Middle upper class women are more likely to utilize impersonal sources such as mass media and physician-supplied information (72). In one study of predominantly working class British women, the mode of exposure to smoking information ranked as follows: 84 percent had seeh it on television; 65 percent were told by family or friends; 52 percent had seen posters and leaflets; 37 percent had been told by husbands; 34 per- cent used books and magazines; and 25 percent had been told by a medical source (16 percent from a doctor, and 9 percent from a nurse) (12). The authors comment that television, posters, and leaflets are inadequate for the delivery of statistical information; books, which are better sources, were used much less than these other sources. Baric and MacArthur present a discussion of health norms in pregnancy , 386 TIMN 0048601

(12). Seventy-nine percent of the sample were aware of some norm relating to smoking in pregnancy: 39 percent thought they were expected not to smoke at all, and an additional 40 percent thought they were expected to reduce their smoking. All of the women could name at least one source of information: 98 percent had been exposed to mass-media messages to quit smoking. Smoking seemed to be undergoing a change in norm status, from generality to specificity; i.e., from being a general health menace to one with specific consequences, such as a threat to the health of the baby. The issue of normative behavior in smoking and per- sonalization of message should be crucial to informational campaigns, according to Fishbein's theory (63). Social support from a spouse should also be critical, as would be involvement of significant others. Women about to have their first baby are more likely to believe educational materials than multiparous women (12, 51a). This finding suggests that different modes of inter- vention or different emphases should be developed for primi- parous and multiparous women. S t I Physician Advice The physician represents one of the most knowledgeable figures the pregnant woman will encounter as a source of information. Consequently, estimates of the frequency with which the physician delivers advice on smoking are of impor- tanc e. Three such estimates are available from national samples in the United States. In the first study, conducted in the mid-1960s, 37 percent of physicians reported that they advised all or almost all (95 to 100 percent) of their pregnant patients to quit smoking or cut down sharply. Obstetricians were more likely to deliver such advice to pregnant patients (49 percent) than were physicians in general practice (38 percent) (74). The Physician Advice Survey conducted by the Center for Disease Control examined the beliefs and behavior of physicians specializing in Obstetrics and Gynecology (OB-GYN) in the United States (41, 13). The OB-GYN specialty practice Includes preventive medical care in the form of specific suggestions regarding hygiene and family planning and,-- during pregnancy, active participation in directing perinatal 387 TIMN 0048602

care (41). The beliefs of OB-GYN specialists about the relationship between maternal srnotcing and neonatal death are presented in Figure 3, along with some of the more common diseases associated with smoking. Because neonatal death can result from a great many factors, the attribution of causality s is somewhat lower than for the other conditions represented. However, it is notable that 23.6 percent of the physicians deny the existence of any relationship. Congruent with the estimate from the 1960s, 45.3 percent of OB-GYN specialists in this survey claimed to instruct all or almost all of their patients to quit or cut down on smoking (see Figure 4). Another 13.1 percent delivered such advice to most or many (65 to 95 percent). A noticeably smaller fraction of physicians who are current smokers deliver this message than ex-srnokers or nonsmokers. The 1975 Survey of Adult Use of Tobacco, sponsored by the National Clearinghouse on Smoking and Health, included a questionnaire directed at smoking habits in pregnant women. A preliminary analysis of the results has been made (85). Out of 12,029 respondents interviewed in 1975, a total of 1,225 women (814 current smokers and 411 former smokers) were administered questions about their smoking habits during pregnancy. Each of the 983 respondents (664 current' smokers and 319 former smokers) who had ever been pregnant was asked whether her doctor suggested that she quit smoking or cut down during her last pregnancy. Table 18 displays the results by year of last pregnancy. The percentage of women reporting such advice from their doctor rose steadily. Only 14.6 percent of women who had last been pregnant from 1965 to 1969 claimed to have been advised by their doctor either to stop or cut down; 23.7 percent of women last pregnant from 1970 to 1975 remembered such advice. These estimates are considerably smaller than those supplied by physicians themselves (174, 41). There are several possible explanations for the discrepancy: the women were reporting retrospectively, and memory may have been distorted; a selective under-reporting of advice may have occurred; or the populations of physicians and patients may be entirely nonoveriapping. Retrospective data have been shown to be unreliable in one pregnancy study (51). Unfortunately, sample sizes were too small to provide reliable estimates of the percentage of women who followed the advice of a physician to stop smoking during pregnancy. Such data might have yielded an estimate of the effectiveness of such advice. 388 ' TIMN 0048603

FIGURE 3.-8ettefs of Ob-Gyn Specialists about the association of Maternal (Smoking with Neonatal Death and other selected diseases) n= 5401 100"- ~ ' a m z 80 "' W CO k7 w U W 0. 60•-' 40- MAJOR i CAUSE / G CONTRIBUTIN ASSOCIATION NO ASSOCIATION 9 90.4 KMAV 78.2 0 ! 23.4 23.6 0 17.4 20 00 ~ 0 0 CORONARY CHRONIC ARTERY sRONCHITIS M DISEASE NEONATAL DEATH PULMONARY EMPHYSE A 92.6 LUNG CANCER i

FIGURE 4 -Percentage of patients advised to quit or cut down their pmoking by the smoking behavior of the advising obstetrician Gyneco4ogist 70 - ADVISE ALL +ALMOST ALL PATIENTS E] MOST +MANY FEW +NONE ' 60- 50 , 1

TABLE 18.-0istribution of responses of current former smokers who were ever pregnant to the question ^Did your doctor suggest that you cut down or stop smoking cigarettes during your last pregnaneyi• Percent by Year of Last Pregnancy Physician's Advice (Prior to 1965) (1965-69) (1970-75) (1965-75) Qu i t smok i ns 5. 6% 6. 39C• 10.894 9. 3% Cut down smoking S.7 8.4 12.9 11.4 No advice•given 70.5 64.1 6Sa6 65.1 Not smoking at ths time 16.4 20.6 9.1 12.9 Had no doctor 0.5 0 0.2 0.1 Don't know or no answer 1.3 0.8 1.3 0.9 Ns983 466 215 291 506 SaURCE: 197S NCiiS survey. 391 TIMN

In sum, over 50 percent of physicians claim to advise their pregnant -patients to etim,inate„ or sharply curtail their smoking durirsg pregnancy, but a much smai ler percentage of pregnant women recall such advice. I I Prevalence of Smoking and Quitting During Pregnancy The prevalence of smoking in pregnant women (before special cessation efforts) should be roughly equivalent to the pre- valence of smoking in the female population in the same age range, corrected for socioeconomic status. Ten studies con- ducted ~ n developed countries, reported between 1971 and ' 1973, show a range from 23.4 percent to 47.6 percent in prevalence of tobacco use (139). The median rate is 42.75 percent smokers for the entire sample. A survey (conducted during the course of the pregnancy) of 9,553 pregnant women who represent a cross section of the general population in the Riverside-San Bernadino-Ontario area (California) was recently completed (104). Preliminary results indicate that 44.5 percent of all women surveyed either continued to smoke during pregnancy or had smoked before, but not during, this pregnancy. Since the precise time of cessation is not clear, a more conservative estimate is that 33.3 percent of women continued to smoke for the duration of their pregnancy. This estimate is well within the range of those derived from the Population Report analysis (139). There is a paucity of race-specific information on smoking prevalence during pregnancy. Niswander and Gordon (128), in a study encompassing 14 U.S. cities, reported greater prevalence of smoking among white than black women 53.65 percent vs. 41.85 percent, respectively. This is a high estimate and reversal of the prevalence rates presented in Tabie 7. The finding Is similar to the previously presented data in that white women smoked more cigarettes per day than black women: only 3.3 percent of black women smokers consume a pack a day or more compared to 13.4 percent of white women in this study. Smoking is slightly less prevalent in black than in white women in the sample of Kuzma and Phillips (104); 57.3 percent of black women and 53.3 percent of white women have never smoked. For Hispanic women, the percentage is somewhat higher, 61.9 percent never-smokers. Table 19 summarizes the results of 11 studies reporting rates of discontinuing smoking during pregnancy. The overall rate of cessation among regular smokers ranges from 0.9 percent 392 TIMN 0048607

t . . . . . ..v~. •. . •.•. v .•. . . . v . . ..•.ti. .'•. r . . ••w•. .-. . . . . . . . > . . . i• . . . . . . . . . . TABLE 19 Percentage of current smokers who alter smoking behavior during pregnancy Change In Smoking Habit-•Percent of Women Quit Cut Down No Author & Date N Quit Temporarily Only • Increased Change Miscellaneous, or Comment 1. Kullander & Kallen, 1971 2,806 0.9 1.3 97.3 +0.5 Initiated 2 Andrews & McGarry, 1972 6,733 14,7 Maternities only 3. Butler et al., 1972 8,341 18.4 Quit by end of 4th month 4. Schwartz et al., 1972 1,188 31.0 10.0 6. 8anc et al., 19761 134 14.9 3.0 82.1 Quit by lst ante•natal visit 6. Graham, 1976 50 33.3' 33.3' 33.3 ' 113 quit or cut down; 1/3 cut down temporarily 7. Saric & MacArthur,19771 133 22.5 6.0 33.1 5.3 26.3 +6.8 reduced temporarily 8. Donovan, 1977 959 0 12.5 6.6 9. Yankelovich et a1.,1977 ? 35.0 32.0 o, 10. Harr is. 1979 4092 26.5 24.8 7.9 36.9 +3.9 changed brand or switched to filter cigarettes 82.2 of quitters resumed ~ I smoking after delivery O 11. Kuzma & Phillips. 1979 4•249 25.13 13.4 of quit smokers were again smoking at 1•5 mo. ~ I post-delivery ~ Note; 1 These two studies may be composed o/ overlapping samples. 201 the 506 women in the NCSH survey whose last pregnancy occurred during 1965-75, 409 reported smoking either before or during pregnancy. 3Percent who smoked prior to, but not during this pregnancy, calculated as part' of smoker sample.

to 35 percent, which is the figure most often anecdotally cited. The median is closer to 20 percent. Only one study provides ethnic data on smoking cessa- tion during pregnancy (104). In this study, it should be remembered, stopped smokers are women who smoked prior to, but not during the pregnancy, so that quitting may not have been pregnancy-specific. Rates are very similar for white, black and Hispanic women: 24.5 percent, 24.9 percent and 28.7 percent respectively, were stopped smokers in this study. Cutting down on smoking during pregnancy would appear to be better than no change in behavior, especial ly for 'those adverse effects upon the fetus which show a dose-response relationship. However, cutting down on number of cigarettes does not always Imply a reduction in delivered dose of nicotine or other tobacco smoke constituents (77, 78). When smoking behavior was measured over the course of pregnancy in regular smokers (5 to 30 cigarettes per day for at (east 5 years), a decrease in number of puffs per cigarette occurred as pregnancy progressed (6). Like puffing rate, the COHb concentration aiso decreased over time in pregnancy. However, in these subjects there was no significant change in nicotine dose extracted from the cigarette over the duration of the pregnancy. Some alteration in puffing pattern, presumably in inhalation, affected the compensation. Thus, caution must be exercised in the Interpretation of "cutting down." There is even less information available on the per- centage of quit-smokers who return to smoking after delivery. Table 19 provides two extremely divergent estimates: 82.2 percent (85) and 13.4 percent (104). Because we are dealing with relatively small sample_ sizes, the reliability of such data Is not very high. Much more information must be accumulated before any firm statements about recidivism can be made. Women who quit during pregnancy have an excel tent opportunity to change a behavior for life, with benefits both to themselves and to their children (see Recommendations). Psychosociat. Factors in Quitting Health reasons, primarily centering around preventing harm to the fetus, are most often given as reasons for quitting. Yankelovich, et al. (203) report that 62 percent of young women smokers befieve that smoking can harm the fetus and norms against smoking have been discussed (11). The sickness 394

experienced as a part of pregnancy can also be a reason to give up smoking (12). It has also been reported that women who smoke before pregnancy show a significantly increased Incidence of appetite cravings and aversions, which may be associated with quitting (41). A closely related aspect of maternal health is weight gain. Preventing excessive weight gain has even been given as a reason to continue smoking during pregnancy (51a). Baric and MacArthur included control of weight gain as a norm during pregnancy; 24 percent of this sample expressed awareness of social expectations In this area (11). The issue of how much weight it Is appropriate to gain in pregnancy varies according to time and culture. So the generality of this finding is unclear. Little Is known about problems in quitting during pregnancy. The role of cigarettes as stimulants or tension reducers may be altered during this period. Abstinence symptomatology has also not been documented. A composite picture of the successful quitter has been drawn by Baric, et at. and.aiso by Kuzma Phillips (12, 104). Baric, et al. list educational qualifications as being positively related to quitting, followed by sickness In early pregnancy (12). Other distinguishing characteristics are smoking., fewer cigarettes before pregnancy (also see 161, 51), having started smoking at an older age, having stoppe¢,.,.previously for at least 6 months, having heard about harmful effects of smoking from more sources,, firmly believing that smoking was hartinful to the baby, and finally, being encouraged to stop or being joined in the cessation effort by their husbands (156, 49). lGuzma and Phillips identified a number of similar characteristics: higher educational level; greater family income; being married; being ernployed; more frequent church attendance; having a spouse who does not smoke; and no illicit drug use (103, 104). The characteristics described--advanced educational level, higher socioeconomic status, wider Information base, belief in stopping for the sake of the fetus, and spousal support--all fit with a model of behavior change involving information, personalization, and social norms (63). Three studies evaluate smoking cessation interventions for pregnant women (12, 51, 40). Tables 9 and 10 show reported abstinence figures for two studies. One study (12) showed no difference between intervention and control groups, and the second study showed 50 percent abstinence at 9- z 3 95 ' TIMN 0048610

month follow-up for those completing treatment (12, 41). This latter result is very encouraging but is based on a very small sample in an affluent community where the afore- mentioned factors of educational level, high socioeconomic status and orientation toward professional advice are operative. ' Recommendations The preceding discussion has revealed a number of findings which may be useful in improving methods of reaching the pregnant woman and offering her cessation interventions. 1. Pregnant women seem to know that smoking is harmful to health, and most acknowledge that it can be directly harmful to the fetus. This information about the baby's health should be made as specific as possible, and the mother's own health should be intricately interwoven in the theme. Quitting is for the good of both mother and baby, not the baby alone. The harmful aspects of smoking and the benefits of not smoking must be equally emphasized. 2. Mass media, such as television and film, are par- ticularly good avenues for portraying women of varying eth- nicity in a number of geographical and socioeconomic settings. In addition, It is important because of gender identification to involve women as the transmitters of information and advice. Information should be dispensed by as many different sources of contact in the prenatal clinic (or doctor's office) as possible, not solely by the physician. The awareness of various, health professionals should be raised in this regard. 3. Social norms and lay referral systems should be used as part of information dissemination and modeling influences. This is particularly true for women of lower socioeconomic status. It is important to involve the father of the child in the normative belief system and in a direct supportive effort of quitting. ' This should be particularly timely in an era when more and more couples are experiencing pregnancy and birth as a two-person process. 44 Much more emphasis must be placed on permanent smoking cessation rather than just during the time of pregnancy. Positive aspects of remaining an ex-smoker inciude better health for the mother and child and the future impact of role modeling as the child grows. 396 TIMN 0048611

SUMMARY 1. The percentage of 17-18 year old women who- smoke has shown a steady rise between 1968 and 1979; it now appears, however, that the increase in smoking prevalence among adolescent females has leveled off and begun to decline. Young women born after 1952 show a substantially reduced initiation of smoking and will probably have a much lower prevalence of smoking as adults. 2. Those young women who do begin to smoke are starting to smoke regularly at a younger age, with more than half of the male and female adolescents who begin to smoke starting before the 10th grade. 3. The earlier tobacco is used and the greater the number of cigarettes smoked per day, the less likely an attempt to quit will be successful. 4. The percentage of women smokers who smoke more than one pack per day Is increasing. 5. Adolescent and adult women are more likely to use low - tar and nicotine cigarettes, smoke fewer cigarettes per day and inhale less deeply than do men, but the difference between the sexes in these patterns of smoking is decreasing. Adolescent and adult black women are more likely to be smokers than their white peers, but they smoke fewer cigarettes per day. 6. Adolescents from low income families, single parent families, and families with lower parental educational levels are more likely to become smokers. 7. Female and male adolescents are more likely to begin smoking if a parent or older sibling also smokes. 8. Adolescent smokers associate with peers who smoke and nonsmokers associate with nonsmoking peers. .9. Adolescent girls overestimate the percentage of their peers who smoke and they have a very positive image of the people in cigarette advertisements, but they are less likely than adolescent boys to see smoking as a social asset. 10. Adolescent girls who smoke tend to be more outgoing but feel less able to influence their future. 11. Adolescents experience stress due to feelings of unattractiveness, incompetency in school achievement and personal relations, limited opportunity for personal growth and concern over future social and economic roles. This stress may be the common mechanism producing the increased rates of smoking in some groups. 12. The factors associated with successful quitting by 397 TjMN 0048612

I adolescents of either sex are lower number of cigarettes smoked per day, higher educational aspirations and achievement, greater acceptance of the health risk of smoking and having more nonsmokers among their friends. 13. It Is possible that women and men modify their smoking in order to maintain a constant nicotine level. 14. Women are more likely than men to smoke in order to reduce stress. 15. Women at higher education and Income levels are more likely to succeed in quitting. Additional factors associated with successful quitting are a strong commitment to change, the use of behavioral techniques and the reliability of social support for quitting. Women have been reported to show lower rates than men of successful cessation following organized cessation programs, a difference which is less apparent in those programs which Include social support. 398 TIMN 0048613

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