Medical Conditions Among Adult Offspring Prenatally Exposed to Diethylstilbestrol
ABSTRACT 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.
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ABSTRACT: Context.Estrogen is critical for bone formation and growth in women. Estrogen exposures occur throughout life, including prenatally, and change with reproductive events, such as menarche and menopause.Objective.The objective of this study was to investigate the association between age at menarche, age at menopause, and years of menstruation with incidence of osteoporosis and assess the impact of prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen, on such associations.Design, Setting, and Participants.Participants were 5,573 women in the National Cancer Institute Combined Cohort Study of DES (1994-2006). Data on reproductive history and medical conditions were collected through questionnaires at baseline in 1994 and subsequently in 1997, 2001, and 2006. Age-stratified Cox regression models were used to calculate multivariable incidence rate ratios (IRR) and 95% confidence intervals (CI). Effect measure modification by prenatal DES exposure was assessed using cubic restricted spline regression models.Main Outcome Measure(s).OsteoporosisResults.The IRRs for osteoporosis incidence with age at menarche <11 years and age at menopause ≥50 years were 0.82 (CI: 0.59, 1.14) and 0.61 (CI: 0.40, 0.92), respectively. Fewer than 25 years of menstruation was associated with an increased incidence of osteoporosis (IRR: 1.80; CI: 1.14, 2.86) compared with ≥ 35 years of menstruation. Associations were stronger among women who had not been prenatally exposed to DES.Conclusions.Our data support the hypothesis that lifetime cumulative exposure to estrogens is protective against osteoporosis. Furthermore, prenatal exposure to estrogen appears to modify these associations, although the mechanism by which this occurs is unknown.The Journal of Clinical Endocrinology and Metabolism 11/2013; 99(2). DOI:10.1210/jc.2013-2954 · 6.31 Impact Factor
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ABSTRACT: Objective To assess the association between in utero exposure to either diethylstilbestrol (DES) or an oral contraceptive in pregnancy and offspring obesity.Methods Using data from the Collaborative Perinatal Project (1959-1974), a multicenter prospective study of pregnant women and their offspring, we examined overweight or obesity among 34,419 children with height and weight data at age 7 years. Generalized linear models to estimate the adjusted odds ratio (aOR) for overweight or obesity (≥85th percentile) or obesity (≥95th percentile) in the offspring according to exposure during different months of pregnancy were used.ResultsOral contraceptive use during pregnancy was positively associated with offspring overweight or obesity and obesity. The magnitude of association was strongest in the first 2 months of pregnancy for obesity (aOR 2.0, 95% CI: 1.1, 3.7). DES use was also associated with offspring overweight or obesity and obesity, with the association being strongest for exposure beginning between months 3 and 5 (e.g., for exposure beginning in months 3-4, the aOR for obesity was 2.8, 95% CI: 1.3, 6.3).Conclusions Pharmacologic sex hormone use in pregnancy may be associated with childhood obesity. Whether contemporary, lower dose oral contraceptive formulations are similarly associated with increased risk of childhood obesity is unclear.Obesity 04/2014; 22(11). DOI:10.1002/oby.20778 · 4.39 Impact Factor