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Smoking and Health 1964-1979 T H E C 0~ KT I N U I N G C 0 N T R 0 V E R S Y T H E T 0 B A C C 0 I N S T I T U T E 1776 K Street, N.W., Washington, D.C. 20006 January 10, 1979

Women and Smoking After two decades of denouncing smoking and claiming "proof" that cigarettes cause various diseases and disorders in men, anti-smoking organizations have in recent years launched special campaigns to persuade women that they, too, are ad- versely affected by cigarettes. Their alarums usually begin with the charge that the woman who smokes in pregnancy may harm her infant. There are claims, too, of reported increases in lung cancer mortality in women as a result of their smoking. Because of this new emphasis on the ladies, we devote a Inconsistent findings from studies of smoking women and their children make it impossible to draw con- vincing conclusions from the data. chapter here to what HEW has called "the smoking-related problems unique to women" (1) -- and a look at some of the unexplainable lung cancer mortality trends for women. Pregnancy Outcome A sizable section of the HEW 1977-78 report to Con- gress on smoking and health'(1) was devoted to smoking women Q C.7 and their pregnancies. It concluded with the strong language Q that cigarette smoking was "probably causally associated" CCjjlN QD 47

C with higher late fetal and infant mortality. However, the 2 actual data mainly relied upon by the HEW authors in reaching this conclusion suggest that any relationship between maternal smoking and pregnancy outcome is far from clear and any claims of causality have highly questionable foundation. The study relied upon by HEW in that last report to Congress was a retrospective analysis at Johns Hopkins of 51,490 births recorded in 10 teaching hospitals in 1960 and 1961 (2). Data were collecte& on infant birth weight, infant mortality, prematurity and placental complications. The statistical analyses of the data on infant mortality indicated that a history of a previous pregnancy loss, the mother's hospital status (private or public patient -- a socioeconomic indicator) and a variable related to age and number of previous pregnancies had "greater effects" on perinatal mortality than maternal smoking level. In their analyses for prematurity and placental complications, the researchers found that previous pregnancy loss and hospital pay status were more strongly related to unfavorable outcomes than maternal smoking level. The reported importance of previous pregnancy history and hospital pay status strongly indicates that a mother's pregnancy experience may well be determined by who the mother is -- her constitution or innate characteristics -- rather than whether or not she smokes. The complexity of all of 48

these findings and the areas to which the data point for further research seem strikingly inconsistent with the unswerv- ing and exclusive emphasis on the mother's smoking habits. Low-Birth-WeiRht Babies Like most other pregnancy studies, the work at Johns Ropkins found that smoking women on average have smaller infants than nonsmokers -- more of what are called low-birth- weight (LBW) babies. LBW infants weigh 2,500 grams -- about 5.5 pounds -- or less. Why and how this happens has not been explained. But the possibility that a common factor predisposes women both to smoke and to have a higher proportion of LBW infants was recently described by the director of a child health study who suggested that "the smoker and not the smoking" may determine whether a woman has an LBW infant (3). Dr. Bea van den Berg took over direction of the large PHS- funded California study from the late Dr. Jacob Yerushalmy, who first proposed, as early as 1964, the hypothesis that a mother's smoking may serve as a marker for -- but not as a causal factor in -- the birth of LBW infants (4). Yerushalmy contended that ineffective randomization and the problem of self-selection in studies comparing smoking and nonsmoking mothers made it difficult to draw any infer- ences from the observation that smokers seem to have more LBW infants (5). In perhaps his best-known study, he identi- 49

fied a group of women who began to smoke after their first children were born (6). Comparing the birth weights of chil- dren born before and after the women began smoking, he dis- covered that both groups of children were lighter than the children of nonsmoking mothers. He said this indicated some women will have smaller infants whether or not they smoke. Two reseachers published data in 1977 that appear to support Yerushalmy's hypothesis. A National Institutes of Health epidemiologist found that differences in mean birth weights of infants born to women who smoked during one pre- gnancy but not another were "more consistent with the self- selection hypothesis" than the causal hypothesis (7). An Australian who worked with records of 1,200 maternity patients concluded his findings were "compatible" with the theory that maternal smoking does not cause LBW but is "an index" of some other factor or factors (8). Perinatal Mortality Any claim that maternal smoking during pregnancy is causally related to increased perinatal mortality is not supported by the scientific evidence. Yerushalmy, for example, found that the mortality rate of LBW infants was considerably lower for those with smoking mothers than for those with nonsmoking mothers (9). He -contended that his data argued against the proposition that cigarette smoking acts as an external factor that interferes with fetal development. 50

In 1978, the editor of the British journal, Public Health, wrote that evidence that small infants of smoking mothers do not share the high mortality of infants of the same weight born to nonsmoking mothers "has been disregarded." He suggested, "We may tell women that if they smoke their baby may be small. But [we] should not claim risk to life" (10). Spontaneous Abortion In the 1973 HEW report to Congress, the last specifi- cally to discuss spontaneous abortion, the authors said several studies had reported finding a significantly higher, dose- related incidence among cigarette smokers. But they conceded that "the lack of control of significant variables other than cigarette smoking does not permit a firm conclusion to be drawn about the nature of the relationship" (11). No firm conclusion about the "nature" of the rela- tionship can be drawn now, either. A recent study by New York researchers did assert that smoking is "a risk factor" for spontaneous abortion (12). However, the researchers found no statistically significant relationship between the amount smoked and the rates of spon- O taneous abortion. Koreover,{their, emphasis on certain data in ~ ~. the study was criticized by another researcher, who said this co tW f ocus magnif ied "the apparent ef f ect of smoking" in the higher- tJ 51

He suggested that if some of the women were smoking "because they were uptight about a floundering pregnancy" that fact "might distort the picture just enough to make it appear that It ` risk age groups -- the younger and older mothers-to-be (13). smoking is an etiologic agent of spontaneous abortion, when in fact it may merely be a more prevalent behavior characteristic in a troubled pregnancy." Failure to consider this and a number of other factors caused him to conclude, he said, that "we are still at a loss for,the cause of spontaneous abortion." That smoking is a risk factor for spontaneous abortion is not supported by other studies, which have failed to show any significant link with smoking. These include two published since 1976 (14, 15). Another, conducted in Sweden, examined a variable that is not always considered. It found that an overall increased risk of spontaneous 0% abortion among smoking women was almost completely due to the fact the pregnancy was unwanted (16). that A British Medical Journal editorial of less than a year ago puts the reported relationship in perspective more succinctly than anything we coul&say: What remains to be established is whether the association between cigarette smoking and spon- taneous abortion is causal...Only by identifying a mechanism by which cigarette smoking could give rise to spontaneous abortion could we be confident of a causal relation (17). 52

Congenital Malformation .&t A physician appearing before an American Cancer Society "forum" on smokin~g stirred the audience with his charge that smoking is "likely to cause birth defects" (18). However, his opinion was not shared by another physician, appearing at a similar ACS "forum" two weeks later. The second doctor said: ...I don't think anyone has identified absolute evidence that this Jcongenital malformationj is a result of the chronic or even~ acute smoking of the mother (19). These conflicting opinions, especially within one anti-smoking organization, reflect the inconclusive scientific findings in this area. Several large-scale population studies have failed to establish a relationship between smoking and congenital malfor- mation (9, 15, 20, 21). Another, examining congenital mal- formation diagnosed during the first five years of life, found that fewer such conditions occurred in children born to women who smoked during pregnancy than to women who never smoked or to women wh~o stopped at some time before becoming pregnant (22). Even the New York researchers who reported an association between smoking and spontaneous abortion concluded, after study of the scientific literature on smoking and infant malforma- 53

tion, "it is unlikely that smoking acts to cause fetal anoma- lies" (12). That emotionalism can override objective analysis in any area of pregnancy and childbirth is illustrated by the headlines which accompanied the release of a study by a'Pitts- burgh pathologist who claimed maternal smoking was related to congenital malformation (23). Although one headline read "Baby Brain Defect Linked to Smoking" (24), examination of the research paper revealed that the pathologist had described this finding only as an "apparent association" that "requires further analysis." This sort of proviso, of course, never appears in headlines. Child Development Another favorite claim of anti-smokers is that smoking during pregnancy retards the subsequent growth and learning ability of the child. In fact, HEW Secretary Califano in early 1978 spoke of the "developmentally disabled" children of smoking mothers (25). The basis for these allegations? Apparently it is data from an on-going perinatal and child follow-up study in Britain which indicated that-the children of smoking mothers lagged behind the children of nonsmoking mothers in physical and mental development (26-28). The authors did note that the 54

effect of smoking during pregnancy is "relatively small" in comparison with the effects of some other factors, such as social class and the number of older and younger children the household (28). in In the British study, the children of smoking mothers were on the average 1 centimeter -- or only about three-tenths of an inch -- shorter than children of nonsmoking mothers (26). There was also a four-month difference in reading ability between the two groups of children (27). But analysis of physical growth showed that a number of other factors were associated with size at age 7. For example, the child of a blue-collar family was on the average 1.3 centimeters shorter than the child of wealthier parents, while the fourth-born child was usually 2.3 centimeters shorter than the first-born. In a later report from the same British study, researchers examined the children at age 11 and measured only minor differences in either height or mental development of children born to smoking and nonsmoking mothers (28). They also reported that these differences were less than the effects of some of the other factors considered. For instance, the difference between a child from a household with no older children and one from a household with three or more was, on the average, 16 months for;general ability, 29 months for w .~ reading, 14 months for mathematics, and 4 centimeters for ~ height. W 0~ 55

The results of the British study were inconsistent i with those of Johns Hopkins researchers who followed children born of smoking and nonsmoking mothers in 1962 and 1963. They reported: "At four and seven years there was no significant difference in either physical measurements or intellectual functioning" (29). Despite such studies, there are still those who look only at whether the mother smoked during pregnancy to explain possible differences in children's growth and learning skills. This shortcoming was apparent in the 1977-78 HEW report to Congress on smoking and health (1). The authors discusse& a California study in which children of smoking mothers were found to be shorter at age five than children of nonsmoking mothers (30). But the HEW'writers didn't indicate that the study showed a difference of only 0.9 centimeters, and that the researchers had attributed nearly 90 percent of the varia- tions to "parental stature alone." Only 2 percent of the .9 centimeter difference could possibly be due to association with smoking -- about 7 one-thousandths of an inch -- according to the California investigators. Oral Contraceptives The scientific literature does not support the claim that oral contraceptive users who stop smoking significantly decrease their disease rates. In other words, there is no 56 i

scientific basis for any assurance that oral contraceptive users are not likely to develop certain diseases if they stop smoking. The new warning insert now required by the Federal Food and Drug Administration in oral contraceptive packages in effect implies such assurance. And the FDA came under attack at a Congressional hearing last fall for its decision requiring the new inserts. Several prominent statisticians who had examined the studies relied upon by the agency in its decision testified (31-34). One noted that: The warning as state& implies that there is a causal effect of cigarette smoking on the incidence of cardiovascular disease. No statistical study can establish causality. At best it can establish a high probability of possible interrelationships (33). The studies which the statisticians criticized claimed to have shown that smokers who use oral contraceptives have an increased risk of cardiovascular disease (35-38). Their censure, the statisticians said, was based on statistical weaknesses, inadequate sample size and other methodological problems in the studies. Some of these weaknesses had been noted by the authors of the original reports: These estimates of risk...still need to be inter- preted with caution, as a number of assumptions have necessarily had to be made in their calculation and the margin of error is likely to be fairly wide (35). It is essential to point out that the mortality estimates used in this paper are based on small 57

numbers and may be subject to large sampling errors. These e-stimates are also subject to upward and downward biases, which may not cancel each other out... The net effect of these various factors cannot be estimated without additional research, preferably in different settings (37). These estimates [death-rates] are based on small numbers and are necessarily approximate. Without more data it is not possible to examine the inter- relationships of age, smoking, and duration of oral contraceptive use...(38). Several witnesses expressed concern that a statisti- cal relationship between oral contraceptive use, smoking and illness may influence scientists to overlook other factors that may explain the observed relationship. Two other researchers urged in the British journal Lancet that scientists not let "preconceived ideas affect objectivity" in examination of other possible hypotheses. Left unanswered in research so far, they wrote, is the con- founding question of self-selection (39). And they asked: Is it possible that the women who smoke and use oral contraceptives (particularly the older group) are simply reflective of a more flamboyant lifestyle which may well include more stress, more alcohol, more medication (including "downers" and "uppers"), or marijuana use?...There seems to be nothing in the data which would answer once and for all the question -- is it the smoker or the smoking which creates risk difference and is it the oral contra- ceptive user or oral-contraceptive use which is at the bottom of it all?. They concluded that "somehow epidemiological and laboratory studies must be designed to distinguish among the 58 ,

possible aetiologies." What they called "the mix of factors", s t which include genetics, they wrote, "may be more complex than we think." Smoking and Early Menopause In a widely publicized study which appeared in 1977, Boston researchers reported they had found that smokers undergo menopause earlier than nonsmokers (40). According to some voluntary health associations and anti-smokers, this appeared to present a health hazard, because onset of change of life supposedly deprives a woman of the "protection" she is believed to have from female sex hormones (estrogens) against cardiovascular disease (CVD) in her reproductive years. Rowever, this claim can be disputed for several reasons. First, the CVD vital statistics don't support such a theory. If women actually lost some form of hormonal protec- tion with the onset of menopause, reported CVD death rates presumably would jump during the menopausal age span -- rather than continue the expected steady increase. An editorial in Lancet examined this question a few months after publica- tion of the Boston research. And it pointed out: O W Mortality statistics io not seem to support the suggestion that the menopause has any effect on the ~ risk of CHD (coronary heart disease), siwce the cJ1 W death-rate from the disease increases steadily with rA advancing age (41). O 59

Two researchers who studied trends in CHD mortality data for women in England and Wales concluded that women do not lose protection from CHD after the menopause (42). Secondly, evidence inconsistent with this claim has been presented in a study of premenopausal women with advanced hardening of the arteries (43). The research~ers found that the women did not have estrogen deficiencies, as might be expected in the hormonal protection theory. Instead, they found that a family history of coronary disease, hypertension or diabetes was "the most consistent single factor" found among the women. r Finally, a study of women who underwent surgery for removal of their ovaries -- a procedure resulting in estrogen deprivation -- reported that they had no more coronary artery disease than an age-matched control group (44). The authors wrote that "our data support previous reports which question the protective effect of estrogen on development of atherosclerotic coronary artery disease." Am~ong the facts that are not mentioned by those claiming a smoking-early menopause link is that other variables have been associated with the onset of menopause. For in- stance, a Public Health Service study of 1,200 women f ound that the median menopausal age tended to be lover in black women and in white women areas (45). from lower income brackets and rural , . 60

The PHS study also pointed to a fact that has been discussed in other studies: that lean women undergo menopause slightly earlier, and the thinner their measured skinfolds, the earlier the change in their menses. The leanness factor also was reported by other researchers in a 1976 study (46). And what everyone has forgotten is that women who smoke have been found to (47-49). be leaner than women who do not So one is lef t to wonder, if leaner women experience earlier menopause, is it because they are leaner, or because they smoke, or because of the kind of persons they are? Women and Lung Cancer Some persons who disapprove of cigarette smoking claim that the larger number of women smoking accounts for their rising lung cancer death rates. This claim does not stand up well under critical scrutiny. A major weakness in the claim can be seen in a comparison of international lung cancer patterns. cancer death rates for U.S. women have reportedly rising faster year to year~than those in men since the 1960s (50). The U. S. situation is drastically different 61 I

that in Europe. In a World Health Organization report, a professor of actuarial science reported in 1977 that while men's lung cancer death rates had risen relatively steeply in five European countries, none of the women's rates had risen significantly. In fact, the over-all lung cancer mor- tality in French women had dropped (51). In the United Kingdom declining rates of increase have been observed in younger women; simultaneously, a downhill trend in male rates has been reported in the older age groups (52). Thus, lung cancer occurrence patterns in women differ in various countries and they are also quite dissimilar from those of males. Even when allowance is made for the later popularity of smoking among women, there is still no consistent trend of increasing lung cancer mortality rates. These data are not at all compatible with the contention that the cause of lung cancer in both sexes is the same agent -- cigarette smoking. Some scientists believe that the recent rise in lung cancer in women is more artificial than real, because physicians order diagnostic tests more frequently now for women patients they know to be smokers. For example, a doctor at the Yale Medical School reported that over a 12-year period hospital records indicated a dramatic increase in the use of sputum smear tests for women lung cancer patients. He commented: "This increase in the search rate for women may t 62

possibly play a role in various recent reports of rising rates of lung cancer in women" (53). Therefore, it is highly likely that more lung cancer among women is being diagnosed because of the more frequent application of diagnostic techniques than in the earlier years -- when many cases might not have been so diagnosed. Often overlooked in the hurried attempts to put the full blame for women's lung cancer on smoking is the fact that the proportion of cases of this disease with the cell type that has been most frequently associated with smoking has changed very little in the past 25 years (54,55). This raises the question of why researchers haven't observed an immense increase in squamous-cell lung cancers if the causal agent is cigarette smoking. Simple explanations for this so-called "epidemic" of lung cancer in women based solely on smoking habits are clearly inadequate. Recent studies have suggested that industrial or occupational exposures may be important in lung cancer causa- tion in women. A study in Los Angeles County reported an increased risk of lung cancer in women who worked as beauti- cians, assemblers and waitresses (56). Increased lung cancer mortality rates for women were reported in counties in the U.S. in which certain heavy, industries are located. In some, the rates for women the general U.S. rate (57). were more than a third higher than 63

The need for further occupational, geographic and r socioeconomic studies of women and disease should be recognized from these and similar research findings. A single-minded focus on smoking hampers the search for lung cancer causation. i i

f References for Women and Smoking 1. U.S. Public Health Service. The Health Consequences of Smoking: 1977-78. U.S. Department of Health, Educa- tion and Welfare. Washington, July 27, 1978, 73 pp. 2. Meyer, M.B., et al. Perinatal Events Associated with Maternal Smoking During Pregnancy. American Journal of Epidemiology 103/5: 464-476, May 1976. 3. van den Berg, B.J. In: LBW In Infants of Smokers Not Related Just to Smoking Itself, by Annette Oestreicher. Ob. Gyn. News 13/4: 1, 27, Feb. 15, 1978. 4. Yerushalmy, J. Mother's Cigarette Smoking and Survival of Infant. American~ Journal of Obstetrics and Gynecology 88/4: 505-518, Feb. 15, 1964. 5. Yerushalmy, J. Self-Selection -- A Major Problem in Observational Studies. Proceedings of the 6th Berkeley Symposium on Mathematical Statistics and Probability, Vol. 4: 329-342, 1972. 6. Yerushalmy, J. Infants Their Mothers Started with Low Birth Weight Born Before to Smoke Cigarettes. American Journal of Obstetrics and Gynecology 112/2: 277-284, Jan. 15, 1972. 7 Silverman, D.T. Maternal Smoking and Birth Weight. American Journal of Epidemiology 105/6: 513-521, June 1977. 8 Donovan, J.W. Randomised Controlled Trial of Anti- Smoking Advice in Pregnancy. tive and Social Medicine 31: British Journal of Preven- 6-12, 1977. 9 Yerushalmy, J. The Relation ship of Parents' Cigarette Smoking to Outcome of Pregn ancy -- Implications as to the Problem of Inferring Causation from Observed Associa- tions. American Journal of Epidemiology 93/6: 443-456, June 1971. 10. Robertson, J.S. Health and Education -- Smoking. Public Health 92/2: 54-55, 1978. 11. U.S. Public Health Service. The Health Consequences of Smoking: 1973. U.S. Department of Health, Education and Welfare. Washington, DREW Pub. No. (HSM) 73-8704, 1973, 249 pp. 65

0 12. Kline, J., et al. Smoking: A Risk Factor for Spontaneous Abortion.w New England Journal of Medicine 297/15: 793- 796, Oct. 13, 1977. 13. McKean, fl.E. Letter: New England Journal of Medicine 289/2: 113, Jan. 12, 1978. 14. Alberman, E., et al. Maternal Factors Associated with Fetal Chromosomal Anomalies in Spontaneous Abortions. British Journal of Obstetrics and Gynecology 83: 621-627, August 1976. 15. Rummler, V.S. The Effect of Cigarette Smoking on the Weight and Length of the New Born. Z. Arztl. Fortbild. 71: 293-297, 1977. 16. Kullander, S., and Kallen, B. A Prospective Study of Smoking and Pregnancy. Acta Obstetrica et Gynecologica Scandanavica 50/1: 83-94, 1971. 17. Editorial. Cigarette Smoking and Spontaneous Abortion. British Medical Journal 1: 259-260, 1978. 18. Ryser, H.J.-P. Statement before the American Cancer Society's National Commission on Smoking and Public Policy, Boston, June 2, 1977. 19. Allen, J.E. Statement before the American Cancer Soci- ety's National Commission on Smoking and Public Policy, Philadelphia, June 16, 1977. 20. Ontario Department of Health. Second Report of the Perinatal Mortality Study in Ten University Teaching Hospitals. Toronto, Canada, Ontario Department of Health, Ontario Perinatal Study Committee, Vol. 1, 1967, 275 pp. 21. Hollingsworth, D.R., et al. Abnormal Adolescent Primi- parous Pregnancy: Association of Race, Human Chorionic Somatomammotropin Production, and Smoking. American Journal of Obstetrics and Gynecology 126/2: 230-237, 1976. 22. van den Berg, B.J. Epidemiologic Observations of Pre- maturity: Effects of Tobacco, Coffee and Alcohol. In: Reed, D.M., and Stanley, F.J., editors. The Epidemiology of Prematurity. Urban ,b Schvarzenberg, Baltimore -- Munich, 1977, pp. 157-176. 23. Naeye, R.L. Relationship of Cigarette Smoking to Congen- ital Anomalies and Perinatal Death: A Prospective I I I I s 66

Study. American Journal of Pathology 90/2: 289-294, February 1978. 24. Naeye, R.L. In: Baby Brain Defect Linked to Smoking, by Dolores Frederick. The Pittsburgh Press, March 12, 1978. 25. Califano, J.A. Address by the Secretary of Health, Education and Welfare before the National Interagency Council on Smoking and Health, Washington, D.C., Jan. 11, 1978. 26. Goldstein, H. Factors Influencing the Height of Seven Year Old Children -- Results from the National Child Development Study. Human Biology 43: 93-111, 1972. 27. Davie, R., et al. From Birth to Seven: The Second Report of the National Child Development Study (1958 Cohort). Longman in association with the National Children's Bureau, London, 1972. 28. Butler, N.R., and Goldstein, H. Smoking in Pregnancy and Subsequent Child Development. British Medical Journal 4: 573-575, 1973. 29. Hardy, J.B., and Mellits, E.D. Does Maternal Smoking During Pregnancy Have a Long-Term Effect on the Child? Lancet 2: 1332-1336, 1972. 30. Wingerd, J., and Schoen, E.J. Factors Influencing Length at Birth and Height at Five Years. Pediatrics 53/5: 737-741, May 1974. 31. Kastenbaum, M.A. Testimony before the Subcommittee on Intergovernmental Relations and Human Resources, Committee on Government Operations, U.S. House of Representatives: Quality of Scientific Evidence in the Food and Drug Administration Regulatory Decisions -- Oral Contraceptive Labeling. Washington, Oct. 4, 1978, pp. 4-26. 32. Cox, G.M. Statement submitted to the Subcommittee on Intergovernmental Relations and Human Resources, Committee on Government Operations, U.S. House of Representatives: Quality of Scientific Evidence in the Food and Drug Administration Regulatory Decisions -- Oral Contraceptive Labeling. Washington, Oct. 4, 1978, 7 pp. 33. Gibbons, J.'D. Testimony before the Subcommittee on Intergovernmental Relations and Human Resources, Committee on Government Operations, U.S. House of Representatives: Quality of Scientific Evidence in the Food and Drug Administration Regulatory Decisions -- Oral Contraceptive 67

Labeling. Washington, Oct. 4, 1978, pp. 28-42. 34. Budne, T.A. Testimony before the Subcommittee on Inter- governmental Relations and Human Resources, Committee on Government Operations, U.S. House of Representatives: Quality of Scientific Evidence in the Food and Drug Administration Regulatory Decisions -- Oral Contraceptive Labeling. Washington, Oct. 4, 1978, pp. 43-55. 35. Mann, J.I., and Inman, W.H. Oral Contraceptives and Death from Myocardial Infarction. British Medical Journal 2: 245-248, 1975. 36. Mann, J.I., et al. Oral Contraceptive Use in Older Women and Fatal Myocardial Infarction. British Medical Journal 2: 445-447, 1976. 37. Jain, A.K. Mortality Risk Associated with the Use of Oral Con~traceptives. Studies in Family Planning 8/3: 50-54, March 1977. 38. Beral, V. Mortality Among Oral-Contraceptive Users. Lancet 2: 727-731, 1977. • 39. Haack, D.G., and McKean, H.E. Letter: Lancet 2: 1024, 1977. 40. Jick, H.J., et al. -Relation Between Smoking and Age of Natural Menopause. Lancet 1: 1354-1355, 1977. 41. Editorial. Coronary Heart Disease in Young Women. Lancet 2: 282-283, 1977. 42. Heller, R.F., and Jacobs, H.S. Coronary Heart Disease in Relation to Age, Sex, and the Menopause. British Medical Journal 1: 472-474, 1978. 43. Engel, H.J., et al. Coronary Artery Disease in Young Women. Journal of the American Medical Association 230/11: 1531-1534, Dec. 16, 1974. 44. Manchester, J.H., et al. Premenopausal Castration and Documented Coronary Atherosclerosis. American Journal of Cardiology 28: 33-38, July 1971. 45. MacMahon, B., and Worchester, J. Age at Menopause: U.S. 1960-1962. Public•Health Service, U.S. Department of Health, Education and Welfare. Washington, DHEW' Pub. No. (HSM) 73-1268, October 1966. 46. Hjortland, M.C., et al. Some Atherogenic Concomitants of Menopause: The Framingham Study. American Journal 68

C of Epidemiology 103/3: 304-311, September 1976. I I 47. Bjelke, E. Variation in Height and Weight in the Nor- wegian Population. British Journal of Preventive and Social Medicine 25: 192-202, 1971. 48. Higgins, M.W. and Kjelsberg, M. Characteristics of Smokers and Nonsmokers in Tecumseh, Michigan. II. The Distribution of Selected Physicial Measurements and Physiologic Variables and the Prevalence of Certain Diseases in Smokers and Nonsmokers. American Journal of Epidemiology 86/1: 60-77, July 1967. 49. Kopczynski, J. Height and Weight of Adults in Cracow. III. Weight by Age and Cigarette Smoking. Epidemiology of Noninfectious Diseases. Epidemiological Review 26/4: 452-464, 1972. 50. Schneiderman, M.A., and Levin, D.L. Epidemiology of Cancer and Tobacco Use: Trends and Trend Indicators. In: Proceedings of the 3rd World Conference on Smoking and Health, 1975, Vol. II. Public Health Service, U.S. Department of Health, Education and Welfare. Washington, DHEW Pub. No. (NIH) 77-1413, 1977, pp. 73-84. 51. Benjamin, B. Trends and Differentials in Lung Cancer Mortality. World Health Statistical Report 30/2: 118-128, 1977. 52. Adelstein, A.M. Current Vital Statistics: Methods and Interpretation. British Medical Journal 2: 983-987, 1978. 53. Feinstein, A.R., and Wells, C.K. Cigarette Smoking and Lung Cancer: The-Problems of "Detection Bias" in Epidemiologic Rates of Disease. Clinical Research 22/3: 555A, April 1974. 54. Harley, H.R.S. Cancer of the Lung in Women. Thorax 31/3: 254-264, June 1976. 55. Kennedy, A. Relationship Between Cigarette Smoking and Histological Type of Lung Cancer in Women. Thorax 28/2: 204-208, March 1973. 56. Menck, H.R., et al. Lung Cancer Risk Among Beauticians and Other Female Workers: Brief Communication. Journal of the National Cancer Institute 59/5: 1423-1425, November 1977. 57. Blot, W.J., and Fraumeni, J.F., Jr. Arsenical Air Pollution and Lung Cancer. Lancet 2: 142-143, 1975. 69