Medical Conditions Among Adult Offspring Prenatally Exposed to Diethylstilbestrol

eSlone Epidemiology Unit, Boston University, Boston, MA
Epidemiology (Cambridge, Mass.) (Impact Factor: 6.2). 03/2013; 24(3). DOI: 10.1097/EDE.0b013e318289bdf7
Source: PubMed


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.

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.

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).

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.
    No preview · Article · Nov 2013 · The Journal of Clinical Endocrinology and Metabolism
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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.
    Preview · Article · Apr 2014 · Obesity
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    ABSTRACT: Diethylstilbestrol (DES) is a non-steroidal estrogen that was commonly prescribed during pregnancy from the late 1940s to 1971. A potent endocrine disruptor, prenatal DES exposure has been linked with reproductive tract malformations, adverse pregnancy outcomes, cancer, infertility and earlier menopause. DES was used for years as a growth promoter in animal production. Some animal studies suggest that prenatal DES exposure is associated with obesity and metabolic disturbances. Using data from the National Cancer Institute DES Follow-Up Study, we evaluated the association between DES and adult obesity, weight gain from age 20 to mid-life, central adiposity and height among 2871 prenatally exposed and 1352 unexposed women between 23 and 52 years of age (median 41.5) at baseline in 1994. DES exposure status was confirmed by prenatal medical record review. We used multivariable log-binomial models to calculate risk ratios (RRs) for obesity in 2006, and linear regression to calculate mean differences in body mass index, weight gain, waist circumference and height. The adjusted RR for DES and obesity was 1.09 [95% confidence interval (CI): 0.97, 1.22], and RRs were 1.23 (CI: 1.07, 1.42) and 1.05 (CI: 0.91, 1.20) for low and high estimated total DES dose, respectively, compared with no exposure. DES-exposed women gained slightly more weight than unexposed women [mean difference, 0.70 kg (CI: -0.27, 1.66)]. This study suggests that prenatal DES exposure may be associated with a small increase in adult obesity.
    No preview · Article · Feb 2015 · Journal of Developmental Origins of Health and Disease
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