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Background: Diethylstilbestrol (DES), a synthetic estrogen that was used in pregnancy, is a prototype endocrine-disrupting chemical. Although prenatal exposure to DES is known to increase risks of vaginal/cervical adenocarcinoma and adverse reproductive outcomes in women, and urogenital anomalies in men, data on nonreproductive medical conditions are lacking., Methods: We estimated hazard ratios and their associated 95% confidence intervals for the associations between prenatal DES exposure and the occurrence of cardiovascular disease, diabetes, osteoporosis, and related conditions among 5590 female and 2657 male offspring followed from 1994 through 2006, adjusted for birth year, cohort, sex, body mass index, smoking status, alcohol use, education, and number of general physical examinations in the past 5 years., Results: Comparing persons exposed prenatally to DES with those who were not exposed, the hazard ratios were 1.21 (95% confidence interval = 0.96-1.54) for diabetes, 1.27 (1.00-1.62) for all cardiovascular disease, 1.18 (0.88-1.59) for coronary artery disease, 1.28 (0.88-1.86) for myocardial infarction, 1.12 (1.02-1.22) for high cholesterol, 1.14 (1.02-1.28) for hypertension, 1.24 (0.99-1.54) for osteoporosis, and 1.30 (0.95-1.79) for fractures. The associations did not differ by dose and timing of DES exposure, nor, in the women, by the presence or absence of vaginal epithelial changes (a marker of DES host susceptibility)., Conclusions: These data raise the possibility that prenatal exposure to DES is associated with several common medical conditions in adulthood, although differential reporting by DES status and residual confounding cannot be ruled out. Further follow-up should assess these findings with validated outcomes and seek to understand the biological mechanisms.

Objective: To develop a risk-factor score that may provide additional guidance to women and their physicians regarding elective bilateral salpingo-oophorectomy at the time of hysterectomy., Methods: From a case-control study conducted from 1992 to 2008 in women residing in eastern Massachusetts or New Hampshire, we selected 1,098 women with invasive ovarian cancer (case group) and 1,363 for the control group who were older than 40 years and had neither hysterectomy nor a personal or family history of breast or ovarian cancer. Using logistic regression, we identified key risk factors and built a risk score. The score was separately assessed in 126 women in the case group and 156 in the control group with excluded prior hysterectomy to determine whether women who developed ovarian cancer could have been distinguished., Results: Summing eight conditions found to be associated with ovarian cancer (Jewish ethnicity, less than 1 year of oral contraceptive use, nulliparity, no breastfeeding, no tubal ligation, painful periods or endometriosis, polycystic ovary syndrome or obesity, talc use), we created a five-level score. Assigning average risk to those with a score of 2, the odds ratios varied from 0.56 (95% confidence interval [CI] 0.42-0.74) for a score of 0-1 to 3.30 (95% CI 2.50-4.35) for a score of 5 or greater (P trend <.001). The risk score was higher for women who developed ovarian cancer after hysterectomy than those who did not (P=.01). Lifetime risks for ovarian cancer for a woman at age 40 years are changed from 1.2% with a 0-1 score to 6.6% with a score of 5 or higher., Conclusion: We developed a risk-assessment tool that can quantify women's risk for ovarian cancer and should be validated in other data sets.

Background: Early life risk factors for breast cancer have been investigated in relation to hormonal, nutritional, infectious, and genetic hypotheses. Recent studies have also considered potential health effects associated with exposure to environmental contaminants in breastmilk., Methods: We analyzed data from a population-based case-control study of women living in Wisconsin. Cases (n = 2016) had an incident diagnosis of invasive breast cancer in 2002-2006 reported to the statewide tumor registry. Controls (n = 1960) of similar ages were randomly selected from driver's license lists. Risk-factor information was collected during structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from multivariable logistic regression., Results: In multivariable models, maternal age and birth order were not associated with breast cancer risk in the full study population. The odds ratio for breast cancer risk associated with having been breast-fed in infancy was 0.83 (95% CI = 0.72-0.96). In analyses restricted to breast-fed women, maternal age associations with breast cancer were null (P = 0.2). Increasing maternal age was negatively associated with breast cancer risk among women who were not breast-fed; the odds ratio for breast cancer associated with each 5-year increase in maternal age was 0.90 (0.82-1.00). Higher birth order was inversely associated with breast cancer risk among breast-fed women (for women with 3 or more older siblings compared with first-born women, OR = 0.58 [CI = 0.39-0.86]) but not among nonbreast-fed women (1.13 [0.81-1.57])., Conclusion: These findings suggest that early life risk factor associations for breast cancer may differ according to breast-feeding status in infancy.

Background: Animal studies suggest that prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) causes epigenetic changes that may be transmitted to the next generation. Specifically, these studies show an elevated incidence of reproductive tumors in the female offspring of prenatally-exposed mice., Methods: We assessed cancer and benign pathology diagnoses occurring in the offspring of women whose prenatal exposure to DES (or lack of exposure) was verified by medical record. Our data arose from 2 sources: the mothers' reports of cancers occurring in 8216 sons and daughters, and pathology-confirmed cancers and benign diagnoses self-reported by a subset of 793 daughters., Results: Although statistical power is limited, our data are consistent with no overall increase of cancer in the sons or daughters of women exposed in utero to DES. Based on pathology-confirmed diagnoses reported by the daughters, we saw no association between DES and risk of benign breast disease or reproductive tract conditions. Based on 3 cases, the incidence of ovarian cancer was higher than expected in the daughters of women exposed prenatally to DES., Conclusions: Our data do not support an overall increase of cancer risk in the sons or daughters of women exposed prenatally to DES, but the number of ovarian cancer cases was greater than expected. While preliminary, this finding supports continued monitoring of these daughters.

Background: Although the associations with cigarette smoking have been explored extensively for invasive breast cancer, the relation to in situ cancer has not previously been examined in depth., Methods: We analyzed data from a population-based case-control study of women living in Wisconsin, Massachusetts, and New Hampshire. Eligible cases of incident breast carcinoma in situ were reported to statewide registries in 1997-2001 (n = 1878); similarly aged controls (n = 8041) were randomly selected from population lists. Smoking history and other risk factor information were collected through structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated from logistic regression models adjusting for potential confounders., Results: In multivariate models, the OR for breast carcinoma in situ among current smokers was 0.8, compared with never-smokers (95% CI = 0.7-1.0). Risk estimates increased towards the null with greater time since smoking cessation. Odds ratios were also less than 1.0 among women who initiated smoking in adolescence (OR = 0.8) or after a full-term birth (OR = 0.7), relative to women who never smoked. The reduced odds ratios associated with current smoking were strongest among women with annual screening mammograms (OR = 0.7; 95% CI = 0.6-0.9). Odds ratios were not less than 1.0 among current smokers without a recent screening mammogram (1.3; 0.9-2.0)., Conclusions: Our findings suggest an inverse association between current smoking and risk of breast carcinoma in situ among women undergoing breast cancer screening.

Background: Diethylstilbestrol (DES) is a synthetic estrogen that was widely prescribed to pregnant women before 1971. DES increases the risk of breast cancer in women who took the drug and the risk of reproductive tract abnormalities in their offspring. Dutch investigators have reported a 20-fold increase in risk of hypospadias among sons of women who were exposed to DES in utero. We assessed this relation in data from an ongoing study of DES-exposed persons., Methods: Several U.S. cohorts of women with documented exposure in utero to DES have been followed by mailed questionnaires since the 1970s. Comparison subjects are unexposed women of the same ages. In 1997, participants were asked about congenital abnormalities in their children. We calculated prevalence odds ratios for the risk of hypospadias in sons of exposed mothers relative to sons of unexposed mothers using generalized estimating equations to adjust for multiple sons per mother and controlling for maternal age at the son's birth., Results: We obtained data from 3916 exposed and 1746 unexposed women. These women reported a total of 13 liveborn sons with hypospadias (10 exposed, 3 unexposed). The prevalence odds ratio for risk of hypospadias among the exposed was 1.7 (95% confidence interval = 0.4-6.8)., Conclusions: Our findings do not support a greatly increased risk of hypospadias among the sons of women exposed to DES in utero, as has been previously reported.

Background: Clinical studies show that maternal cigarette smoking reduces pregnancy estrogen levels. Women prenatally exposed to maternal cigarette smoke may, therefore, have a lower breast cancer risk because the fetal mammary gland's exposure to maternal estrogen is decreased. Associations between prenatal maternal cigarette smoke exposure and breast cancer, however, have not been observed in previous case-control studies that relied on exposure assessment after the onset of cancer. At the start of this study, cigarette smoking history was obtained directly from the mother., Methods: The National Cooperative DES Adenosis project was a follow-up study of health outcomes in women prenatally exposed to diethylstilbestrol (DES). At the start of the study, women's mothers provided information about cigarette smoking habits during the time they were pregnant with the study participant. In the current study, the breast cancer rates are compared among 4031 women who were or were not prenatally exposed to maternal cigarette smoke. The resultant relative rate (RR) is adjusted for potential confounding by other breast cancer risk factors using Poisson regression modeling., Results: Fetal exposure to maternal cigarette smoke appeared to be inversely associated with breast cancer incidence (RR = 0.49; 95% confidence interval [CI] = 0.24-1.03). The inverse association was more apparent among women whose mothers smoked 15 cigarettes or fewer per day than among daughters of heavier smokers. There were, however, too few cases to precisely estimate a possible dose-response relationship., Conclusion: These results support the hypothesis that in utero exposure to maternal cigarette smoke reduces breast cancer incidence.

Background: Between 1939 and the 1960s, the synthetic estrogen diethylstilbestrol (DES) was given to millions of pregnant women to prevent pregnancy complications and losses. The adverse effects of prenatal exposure on the genitourinary tract in men and the reproductive tract in women are well established, but the possible effects on psychosexual characteristics remain largely unknown., Methods: We evaluated DES exposure in relation to psychosexual outcomes in a cohort of 2,684 men and 5,686 women with documented exposure status., Results: In men, DES was unrelated to the likelihood of ever having been married, age at first intercourse, number of sexual partners, and having had a same-sex sexual partner in adulthood. DES-exposed women, compared with the unexposed, were slightly more likely to have ever married (odds ratio [OR] = 1.1; confidence interval [CI] = 1.0-1.4) and less likely to report having had a same-sex sexual partner (OR = 0.7; CI = 0.5-1.0). The DES-exposed women were less likely to have had first sexual intercourse before age 17 (OR = 0.7; CI = 0.6-0.9) or to have had more than one sexual partner (OR = 0.8; CI = 0.7-0.9). There was an excess of left-handedness in DES-exposed men (OR = 1.4; CI = 1.1-1.7) but not in DES-exposed women. DES exposure was unrelated to self-reported history of mental illness in women., Conclusions: Overall, our findings provide little support for the hypothesis that prenatal exposure to DES influences the psychosexual characteristics of adult men and women.