Risk factors for diethylstilbestrol-associated clear cell adenocarcinoma.

OBJECTIVE: To assess the influence of postnatal factors on the development of clear cell adenocarcinoma in women exposed to diethylstilbesterol (DES), particularly factors related to exogenous or endogenous hormone exposures, and to reassess the relation of season of birth. METHODS: For the analysis of postnatal factors, 244 cases were compared with 244 age-matched DES-exposed women. Information was obtained from telephone interviews, with questions asked in reference to an index age, the age at which clear cell adenocarcinoma was diagnosed. For the analysis of season of birth, 604 cases, living or deceased, were compared with 1749 DES-exposed women. RESULTS: Neither oral contraceptive (OC) use nor pregnancy was associated with risk of clear cell adenocarcinoma: the odds ratios (OR) were 1.1 (95% confidence interval [CI] 0.7, 1.8) for OC use and 1.3 (95% CI 0.7, 2.3) for pregnancy. The OR for fall season of birth relative to all other seasons was 1.2 (95% CI 0.9, 1.4). CONCLUSION: Pregnancy and OCs do not increase risk of DES-associated clear cell adenocarcinoma. In addition, season of birth does not appear to be a material factor; the previous finding of an increased risk for fall season of birth is most likely not valid and probably a chance finding due to small sample size.

Weight gain and the risk of developing insulin resistance syndrome.

OBJECTIVE: Obesity and weight gain have been associated independently with hypertension, hyperinsulinemia, and dyslipidemia; however, prior research has not looked at the relation between weight gain from early adulthood to middle age and the development of this cluster of risk factors, known as insulin resistance syndrome. RESEARCH DESIGN AND METHODS: The association between weight gain over 30 years (defined as the difference between measured weight in middle age and participant recall of their weight at age 20) and the odds of developing insulin resistance syndrome at middle age was examined in a population-based sample of 2,272 eastern Finnish men. RESULTS: Each 5% increase in weight over the reported weight at age 20 was associated with nearly a 20% greater risk of insulin resistance syndrome by middle age, after adjustment for age and height. Moreover, there was a strong graded association between categories of weight gain and risk of insulin resistance syndrome. Men with weight increases of 10-19%, 20-29%, or > or =30% since age 20 were 3.0, 4.7, or 10.6 times more likely to have insulin resistance syndrome, respectively, by middle age, compared with men within 10% of their weight at age 20. Adjustments for age, height, physical activity, smoking, education, and parental history of diabetes did not alter these findings. CONCLUSIONS: The odds of having developed the hemodynamic and metabolic abnormalities that characterize insulin resistance syndrome by middle adulthood were increasingly higher the greater the weight gain over the preceding 30 years. This study adds to the literature identifying deleterious effects of weight gain from young to middle adulthood.

DES awareness and exposure: the 1994 California Behavioral Risk Factor Survey.

INTRODUCTION: Diethylstilbestrol (DES), a drug used in millions of pregnancies between 1938 and 1971, is the first known human transplacental carcinogen. DES is also associated with other serious health problems for those exposed to it either in utero or while pregnant; however, many men and women are unaware of their exposure or how to protect their health. This first population-based study of DES awareness is part of the National Cancer Instututes's National DES Education Program. METHODS: In 1994, 2,077 women and 1,625 men 23 years of age and over responded to the California Behavioral Risk Factor Survey (BRFS). These subjects were either born during the years DES was in use (men and women 23-53 years old in 1994) or could have been pregnant during those years (women 39 years or older). RESULTS: Analyses weighted to the 1994 California age and ethnicity distribution indicate that only 43% of women and 22% of men had over heard of DES (P < .001). Although 44% of Caucasians had heard of DES, only 10% of Hispanics, 27% of African Americans, and 24% of other races had heard of DES. Within each group, women had heard of DES significantly more often than men. Only 17% of women and 5% of men had ever tried to confirm whether they were exposed to DES in utero, and 8% of women whether they were exposed while pregnant. CONCLUSIONS: Given the serious health consequences of DES exposure and available prevention strategies, this lack of awareness warrants an immediate educational effort.

Moderately intense physical activities and high levels of cardiorespiratory fitness reduce the risk of non-insulin-dependent diabetes mellitus in middle-aged men.

BACKGROUND: Physical activity has been advocated as an important factor in the primary prevention of non-insulin-dependent diabetes mellitus (NIDDM), but information concerning the specific intensities and durations that are protective has been unavailable. OBJECTIVE: To examine prospectively the association between self-reported levels of the intensity and duration of physical activities, and cardiorespiratory fitness (assessed by respiratory gas exchange) and incident cases of NIDDM (assessed by the oral glucose tolerance test) in a population-based sample of 897 middle-aged Finnish men. RESULTS: After adjustment for age, baseline glucose values, body mass index, serum triglyceride levels, parental history of diabetes, and alcohol consumption, moderately intense physical activities (> or = 5.5 metabolic units) that were undertaken for at least a 40-minute duration per week were associated with a reduced risk of NIDDM (odds ration [OR], 0.44; 95% confidence interval [CI], 0.22-0.88). Activities with less than an intensity of 5.5 metabolic units, regardless of their duration, were not protective. Cardiorespiratory fitness levels greater than 31.0 mL of oxygen per kilogram per minute were protective against NIDDM (OR, 0.26; 95% CI, 0.08-0.82). A subgroup of men at high risk of NIDDM, because they were overweight and were hypertensive and had a positive parental history of NIDDM, who engaged in moderately intense physical activities above the 40-min/wk duration reduced their risk of NIDDM by 64% compared with men who did not participate in such activities. CONCLUSIONS: After adjustment for age, baseline glucose levels, and known risk factors, physical activities with an intensity of 5.5 metabolic units or greater and a duration of 40 minutes or greater per week protected against the development of NIDDM. These protective effects were even more pronounced in a subgroup of men who were at high risk for the development of the disease.

Increased risk of non-insulin dependent diabetes mellitus at low plasma vitamin E concentrations: a four year follow up study in men.

OBJECTIVE: To investigate whether low vitamin E status is a risk factor for incident non-insulin dependent diabetes mellitus. DESIGN: Population based follow up study with diabetes assessed at baseline and at four years. SETTING: Eastern Finland. SUBJECTS: Random sample of 944 men aged 42-60 who had no diabetes at the baseline examination. INTERVENTION: Oral glucose tolerance test at four year follow up. MAIN OUTCOME MEASURES: A man was defined diabetic if he had either (a) a fasting blood glucose concentration > or = 6.7 mmol/l, or (b) a blood glucose concentration > or = 10.0 mmol/l two hours after a glucose load, or (c) a clinical diagnosis of diabetes with either dietary, oral, or insulin treatment. RESULTS: 45 men developed diabetes during the follow up period. In a multivariate logistic regression model including the strongest predictors of diabetes, a low lipid standardised plasma vitamin E (below median) concentration was associated with a 3.9-fold (95% confidence interval 1.8-fold to 8.6-fold) risk of incident diabetes. A decrement of 1 mumol/l of uncategorised unstandardised vitamin E concentration was associated with an increment of 22% in the risk of diabetes when allowing for the strongest other risk factors as well as serum low density lipoprotein cholesterol and triglyceride concentrations. CONCLUSIONS: There was a strong independent association between low vitamin E status before follow up and an excess risk of diabetes at four years. This supports the theory that free radical stress has a role in the causation of non-insulin dependent diabetes mellitus.

Prevention of non-insulin-dependent diabetes mellitus with physical activity.

Physical activity has been recommended by physicians in managing patients with noninsulin-dependent diabetes mellitus (NIDDM); however, it is unclear whether physical activity can prevent this disease. Several prospective studies have suggested that increased physical activity may lead to the prevention of NIDDM. In the University of Pennsylvania Alumni Health Study, 5990 men were surveyed to determine the relationship between physical activity and the development of NIDDM. A total of 202 men developed NIDDM from 1962 to 1976. Leisure-time physical activity, expressed in kilocalories (kcal) was inversely related to the development of NIDDM. Incidence rates declined as energy expenditure increased. For each 2000-kcal increment in energy expenditure, the risk of NIDDM was reduced by 24% [relative risk (RR) 0.76, 95% confidence interval (CI) 0.63-0.92]. This association remained when adjusting for obesity, hypertension, and parental history of diabetes. The protective effect of physical activity was strongest in individuals at highest risk for NIDDM. Based on the review of data from several large prospective studies, it is quite likely that increased levels of physical activity are effective in preventing NIDDM, and the protective benefit is especially pronounced in those individuals who have the highest risk of disease.

Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus.

BACKGROUND: Physical activity is recommended by physicians to patients with non-insulin-dependent diabetes mellitus (NIDDM), because it increases sensitivity to insulin. Whether physical activity is effective in preventing this disease is not known. METHODS: We used questionnaires to examine patterns of physical activity and other personal characteristics in relation to the subsequent development of NIDDM in 5990 male alumni of the University of Pennsylvania. The disease developed in a total of 202 men during 98,524 man-years of follow-up from 1962 to 1976. RESULTS: Leisure-time physical activity, expressed in kilocalories expended per week in walking, stair climbing, and sports, was inversely related to the development of NIDDM: The incidence rates declined as energy expenditure increased from less than 500 kcal to 3500 kcal. For each 500-kcal increment in energy expenditure, the age-adjusted risk of NIDDM was reduced by 6 percent (relative risk, 0.94; 95 percent confidence interval, 0.90 to 0.98). This association remained the same when the data were adjusted for obesity, hypertension, and a parental history of diabetes. The association was weaker when we considered weight gain between the time of college attendance and 1962 (relative risk, 0.95; 95 percent confidence interval, 0.90 to 1.00). The protective effect of physical activity was strongest in persons at highest risk for NIDDM, defined as those with a high body-mass index, a history of hypertension, or a parental history of diabetes. These factors, in addition to weight gain since college, were also independent predictors of the disease. CONCLUSIONS: Increased physical activity is effective in preventing NIDDM, and the protective benefit is especially pronounced in persons at the highest risk for the disease.

Epithelial ovarian cancer and coffee drinking.

A recent report from a case-control study in Greece suggested that coffee consumption is related to an increase in the risk of ovarian cancer. This hypothesis was examined in a hospital-based case-control study in the US. Information on coffee drinking and other factors was obtained from 290 incident cases of epithelial ovarian cancer and compared with that of 580 controls with non-malignant conditions of acute onset and 476 controls with cancer of other sites. Adjustment was made for the potential confounding effects of several factors, including the major known risk factors for ovarian cancer. The estimated relative risk for drinking five or more cups of coffee per day, relative to none, was 1.1 (95% confidence interval, 0.6-2.0) using the controls with non-malignant conditions and 1.0 (0.5-1.8) using the controls with cancer. The estimates for drinking less than five cups per day were greater than 1.0, but this could have been due to chance. The consumption of decaffeinated coffee and tea also appeared to have no influence on risk. The evidence from this study suggests that, if coffee drinking increases the risk of ovarian cancer, the effect is small.

Risk factors for breast cancer in black women.

Risk factors for breast cancer were examined in black women in a hospital-based case-control study of 529 black women with breast cancer and 589 controls. Late age at menarche was associated with a reduced risk of breast cancer. Women having 5 or more children had a reduced risk relative to that of women with fewer or no children. Late age at first birth was associated with an elevated risk of breast cancer. Among postmenopausal black women, obesity [as measured by body mass index (BMI)] was associated with an increased risk; among premenopausal women, there was no association of breast cancer with BMI. Women whose menopause occurred at or after age 50 were at increased risk relative to those whose menopause occurred earlier. There was no association between number of years of education and breast cancer in black women. History of benign breast disease and history of breast cancer in mother or sisters both were risk factors. The risk factor profile for breast cancer in black women was similar to that observed in whites.

Venous thromboembolism in relation to oral contraceptive use.

The relation of the risk of venous thromboembolism to the use of oral contraceptives was assessed in a hospital-based study of 61 women suffering from a first episode of idiopathic deep vein thrombosis or pulmonary embolism (cases) and 1278 women admitted for trauma or respiratory infections (controls). Twenty (33%) of the cases and 121 (9%) of the controls had used oral contraceptives within the previous month, yielding an age-adjusted relative risk estimate of 8.1 (95% confidence interval 3.7 to 18) for recent users relative to never-users. For women using oral contraceptives containing less than 50 micrograms estrogen, the relative risk estimate was 11 (3.7 to 22); for preparations with 50 micrograms estrogen, it was 5.5 (2.1 to 15); and for preparations with more than 50 micrograms estrogen, it was 11 (3.9 to 30). Past use of oral contraceptives was not associated with an increased risk. The data suggest that the risk of venous thromboembolism is increased for recent oral contraceptive users relative to nonusers, even if women use oral contraceptives containing low doses of estrogen. Confidence intervals were wide, however, so that a reduction in the risk for users of lower dose formulations relative to users of higher dose formulations cannot be ruled out. Selection bias, if present, would have resulted in overestimation of the relative risk, but should not have distorted the comparisons according to dosage.

Does gallbladder removal protect against subsequent myocardial infarction?

It has been suggested that gallbladder removal may protect against subsequent development of myocardial infarction because of increased gastrointestinal cholesterol excretion resulting from increased enterohepatic cycling. To test this hypothesis, the authors used data from two large case-control studies of myocardial infarction--one conducted in 1976-1979 in 155 US hospitals and one conducted in 1980-1983 in 78 US hospitals. First, 550 female myocardial infarction cases were compared to 1,658 controls. Simultaneously adjusting for possible confounding variables using logistic regression, the odds ratio for development of a myocardial infarction subsequent to cholecystectomy was 0.8 (95% confidence interval, 0.5-1.1). Second, 1,511 male myocardial infarction cases were compared to 3,837 controls. With similar adjustments, the odds ratio was 0.8 (95% confidence interval, 0.5-1.2). The risk did not decline as the interval following cholecystectomy increased. The present data are compatible with a protective effect of cholecystectomy on the risk of subsequent myocardial infarction, but they are not conclusive.

The risk of myocardial infarction 10 or more years after vasectomy in men under 55 years of age.

To evaluate whether vasectomy is associated with a subsequent increase in the incidence of myocardial infarction 10 or more years after surgery and whether an effect is more pronounced in those already predisposed to a myocardial infarction, a hospital-based case-control study was carried out in men aged less than 55 years. The men were interviewed during 1980-1983 in 78 hospitals in Massachusetts, Rhode Island, Connecticut, and New York. Among 2,238 men with first episodes of myocardial infarction, 332 (15%) had undergone vasectomy, compared with 572 (16%) of 3,361 controls. Vasectomy greater than or equal to 10 years earlier was reported by 150 cases and 180 controls, to yield a multivariate relative risk estimate of 1.0 after allowance for potential confounding factors (95% confidence interval (Cl) = 0.8-1.3); for vasectomy greater than or equal to 15 years before, based on 34 cases and 33 controls, the estimate was 1.1 (95% Cl = 0.7-2.0). In men predisposed to myocardial infarction because of more advanced age, cigarette smoking, elevated cholesterol level, hypertension, angina pectoris, or other risk factors, vasectomy did not appear to increase the risk further, even after intervals of greater than or equal to 10 years. The results provide evidence against an increased risk of myocardial infarction greater than or equal to 10 years after vasectomy overall and in those known to be predisposed because of other risk factors.

PIP: A hospital-based case-control study was conducted in men under age 55 to evaluate whether vasectomy is associated with a subsequent increase in the incidence of myocardial infarction 10 or more years after surgery and whether an effect is more pronounced in those already predisposed to a myocardial infarction. The men were interviewed during 1980-83 in 78 hospitals in Massachusetts, Rhode Island, Connecticut, and New York. A standard questionnaire was used to obtain information on history of vasectomy, personal characteristics, medical history, cigarette smoking, coffee and tea consumption, history of drug use, and other factors. In addition, the Framingham Type A Personality Scale questionnaire was administered, in which a higher score indicates a greater tendency to Type A behavior, and the men were asked about leisure time physical activities during the year before admission. After discharge, the diagnosis that led to admission was abstracted from the medical record. The participation rate was 87% among the potential cases and 93% among the potential controls. All cases were interviewed men 20-54 years of age admitted for a 1st episode of myocardial infarction, the diagnosis of which met WHO criteria. Men for whom it was judged that the myocardial infarction could have been caused by preexisting heart disease were excluded. There were 2238 cases: median age, 46 years; 97% white. All controls were interviewed men from the pool of potential controls who were 20-54 years old, had no history of myocardial infarction, and were admitted for diagnoses judged to be unrelated to vasectomy. There were 3361 controls: median age, 42 years; 96% white. Among the 2238 cases, 332 (15%) reported having had a vasectomy, compared with 572 (16%) of 3361 controls. Vasectomy more than 10 years previous was reported by 150 cases and 180 controls to yield a multivariate relative risk estimate of 1.0 after allowance for potential confounding factors; for vasectomy more than 15 years previous, based on 34 cases and 33 controls, the estimate was 1.1. In men predisposed to myocardial infarction because of more advanced age, cigarette smoking, elevated cholesterol level, hyperstension, angina pectoris, or other risk factors, vasectomy did not appear to increase the risk further, even after intervals of more than 10 years. The results offer evidence against an increased risk of myocardial infarction more than 10 years after vasectomy overall and in those known to be predisposed because of other risk factors.

The risk of myocardial infarction after quitting smoking in men under 55 years of age.

We assessed the effect of quitting cigarette smoking on the incidence of nonfatal myocardial infarction in men under the age of 55 in a case-control study of 1873 men with first episodes of myocardial infarction and 2775 controls. For "current" smokers (men who had smoked in the previous year) as compared with those who had never smoked, the estimated relative risk of myocardial infarction, adjusted for age, was 2.9 (95 per cent confidence interval, 2.4 to 3.4). Among exsmokers (those who had last smoked at least one year previously), the relative-risk estimate declined to a value close to unity for those who had abstained for at least two years; the estimate was 2.0 (1.1 to 3.8) for men who had abstained for 12 to 23 months, and the estimates were about 1.0 for men who had abstained for longer intervals. The results were unchanged by allowance for multiple potential confounding factors. A similar pattern was apparent among exsmokers who had smoked heavily for many years; among those predisposed to a myocardial infarction because of family history, hypertension, or other risk factors; and among those with no apparent predisposition. The results suggest that the risk of myocardial infarction in cigarette smokers decreases within a few years of quitting to a level similar to that in men who have never smoked.

Evidence for an increased risk of Crohn's disease in oral contraceptive users.

The risk of Crohn's disease in relation to oral contraceptive use was evaluated in a hospital-based, case-control study of 57 women with Crohn's disease and 2189 controls with other conditions. The relative risk for oral contraceptive users compared with women who had never used these drugs was 1.9 (95% confidence interval 1.0-3.5). The magnitude of the relative risk estimate was related to the timing and duration of oral contraceptive use. For use within the year before admission to a hospital (recent use), the relative risk estimate was 4.3 (2.1-8.7); the estimate dropped to 1.2 (0.5-2.6) 4 yr after discontinuation of oral contraceptive use. The relative risk estimate for recent use that lasted greater than or equal to 5 yr was 8.0 (3.1-21). The findings are in accordance with earlier reports of an increased risk of Crohn's disease in oral contraceptive users.

Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens.

In a case-control study of the risk of adenocarcinoma of the endometrium in relation to conjugated-estrogen use, we found that 31 per cent of 425 women with endometrial cancer and 15 per cent of 792 controls reported having used conjugated estrogens; the rate-ratio estimate was 3.5 with a 95 per cent confidence interval of 2.6 to 4.7. For use that lasted at least one year, the rate-ratio estimate for Stage I or II cancer was 5.2 (95 per cent confidence interval, 3.7 to 7.2), and for Stages III and IV combined it was 3.1 (1.5 to 6.4). Among women who had used estrogen for at least one year and then discontinued it, the risk of endometrial cancer remained significantly elevated even after estrogen-free intervals of over 10 years. The findings suggest that long-term use of conjugated estrogen increases the risk of both localized and widespread endometrial cancer. The data also suggest that women who have taken conjugated estrogen for one or more years remain at increased risk for at least 10 years after they discontinue use. Such women should be considered for long-term gynecologic surveillance.

Cigarette smoking and the risk of endometrial cancer.

Because of evidence of reduced estrogen excretion in the urine of women who smoke cigarettes and evidence linking estrogen levels to the risk of cancer of the female reproductive system, we evaluated the risk of endometrial cancer in relation to cigarette use in a hospital-based case-control study of 510 women with endometrial cancer (cases) and 727 women with other cancers (controls). The rate-ratio estimate (relative risk) for current smokers as compared with women who had never smoked was 0.7 (95 per cent confidence interval, 0.5 to 1.0), and for former smokers the estimate was 0.9 (0.6 to 1.2). For women currently smoking 25 or more cigarettes per day, the rate-ratio estimate was 0.5 (0.3 to 0.8). The effect of current smoking of at least 25 cigarettes per day appeared to be confined to postmenopausal women, among whom the estimate was 0.5 (0.2 to 0.9). Among premenopausal women the estimate was 0.9 (0.4 to 2.2), but the difference between these two estimates could have been due to chance. The data suggest that women who smoke heavily may have a lower risk of endometrial cancer than nonsmokers. The present findings do not have direct public health importance since cigarettes, overall, have serious deleterious effects. However, if these results are confirmed, elucidation of the underlying mechanisms whereby smoking reduces the risk would be of interest and might be useful in the development of strategies for preventing endometrial cancer.

Breast cancer and the consumption of coffee.

The hypothesis has been raised that coffee consumption may increase the incidence of breast cancer, based on the report that fibrocystic breast disease, a risk factor for breast cancer, regresses after abstention from coffee and other methylxanthines. The relation between recent coffee consumption and the risk of breast cancer was evaluated in a case-control study, based on interviews conducted 1975-1982 at several mainly eastern US teaching and community hospitals. The responses of 2,651 women with newly diagnosed breast cancer were compared with those of 1,501 controls with nonmalignant conditions and 385 controls with cancers at other sites. The relative risk estimates for levels of coffee drinking up to seven or more cups daily, relative to none, approximated 1.0 with narrow 95% confidence intervals. After allowance for confounding, the relative risk estimate for drinking at least five cups a day was 1.2 (95% confidence interval, 0.9-1.6) using the noncancer controls and 1.1 (0.7-1.6) using the cancer controls. Coffee consumption was not associated with an increase in the risk of breast cancer among women with a history of fibrocystic breast disease, nor were tea or decaffeinated coffee associated with an increase in the risk of breast cancer. The results suggest that the recent consumption of coffee does not influence the incidence of breast cancer.

Myocardial infarction and cigarette smoking in women younger than 50 years of age.

The modifying influence of individual risk factors on the relation between myocardial infarction (MI) and cigarette smoking was evaluated in a case-control study of women younger than 50 years of age. Data from 555 women who survived first MIs were compared with those of 1,864 hospital controls of similar ages. The risk of MI increased with the number of cigarettes smoked, both in the presence and absence of factors that predispose to an infarction. In particular, the association was apparent at all ages, at all levels of total serum cholesterol and high-density lipoprotein cholesterol, and in the presence and absence of oral contraceptive use, hypertension, diabetes mellitus, blood group A, tendency to type A behavior, and family history of MI. The relative increase in risk was generally greater the lower the underlying predisposition to MI. There was clear evidence, however, that recent oral contraceptive use substantially augmented the increased risk for smokers, and hypercholesterolemia may have had the same effect.

Alcoholic beverages and myocardial infarction in young men.

Previous studies have suggested that people who consume a moderate amount of alcohol have a reduced risk of coronary heart disease compared with nondrinkers. This hypothesis was further tested in the period April 1980-April 1983 in a study of 2,170 men with first nonfatal myocardial infarction and 981 hospital controls, all under 55 years of age. The relative risk estimate for men who drank between one and seven times per week compared with never drinkers was 1.2 (95% confidence interval, 0.8-1.8) when age and cigarette smoking were taken into account and 1.1 (0.7-1.7) when personality type was also taken into account. There was no evidence of a reduced risk for users who drank primarily one type of alcoholic beverage (beer, wine, or liquor) or within categories of dose measured in ounces consumed per week. The findings were not materially changed when other risk factors for myocardial infarction were taken into account. The results of this study suggest that moderate alcohol consumption does not reduce the risk of nonfatal myocardial infarction.

Noncontraceptive estrogen use and the risk of breast cancer.

The relation between the risk of breast cancer and the use of noncontraceptive estrogens was investigated in a hospital-based study of 1,610 women with breast cancer and 1,606 with other conditions. The overall relative risk estimate for conjugated estrogens first taken at least 18 months before admission, compared with never-use of any noncontraceptive estrogens, was 0.9 (95% confidence interval, 0.7 to 1.1). For other estrogens first taken at least 18 months before admission, the estimate was 0.8 (0.6 to 1.1). The results were similar when known risk factors for breast cancer were taken into account. Among postmenopausal women, conjugated estrogens did not appear to increase the risk of breast cancer, even when taken for many years or in the distant past. There was no evidence of an increased risk due to conjugated estrogen use among subgroups of women defined according to various risk factors for breast cancer. The results of this study suggest that noncontraceptive estrogens do not increase the risk of breast cancer.