Prenatal Diethylstilbestrol Exposure and Risk of Uterine Leiomyomata in the Nurses' Health Study II

Abstract

Previous studies evaluating the association of prenatal exposure to diethylstilbestrol (DES), a potent endocrine disruptor, with incidence of uterine leiomyomata (UL) have had conflicting results. We evaluated the association between prenatal DES exposure and incident UL in women in the Nurses' Health Study II from 1989 to 2009. Women were aged 25-42 years at enrollment and had a prenatal exposure window corresponding to DES use. The analytical sample was larger than previous studies and included 102,164 premenopausal women with intact uteri, no prior history of UL or cancer, and prenatal DES exposure. Multivariable-adjusted Cox proportional hazard models were used to estimate the relationship between DES exposure and UL risk. During 1,273,342 person-years of follow-up, there were 11,831 incident cases of UL. Women with prenatal exposure to DES had a higher incidence of UL compared with unexposed women, with an adjusted hazard ratio of 1.12 (95% confidence interval: 0.98, 1.27). Risk was strongest for women exposed to DES in the first trimester, when exposure corresponds to early stages of fetal Müllerian development (adjusted hazard ratio = 1.21, 95% confidence interval: 1.02, 1.43). These results suggest that first-trimester DES exposure may be associated with an increased risk of UL, but they must be interpreted with concern for detection and recall biases.