Background: Prenatal exposure to diethylstilbestrol (DES), an endocrine-disrupting chemical, may be associated with depression in adulthood, but previous findings are inconsistent.
Methods: Women (3,888 DES exposed and 1,729 unexposed) and men (1,021 DES exposed and 1,042 unexposed) participating in the National Cancer Institute (NCI) DES Combined Cohort Follow-up Study were queried in 2011 for any history of depression diagnosis or treatment. Hazard ratios (HRs; 95% confidence intervals [CIs]) estimated the associations between prenatal DES exposure and depression risk.
Results: Depression was reported by 993 (26%) exposed and 405 (23%) unexposed women, and 177 (17%) exposed and 181 (17%) unexposed men. Compared with the unexposed, HRs for DES and depression were 1.1 (95% CI = 0.9, 1.2) in women and 1.0 (95% CI = 0.8, 1.2) in men. For medication-treated depression, the HRs (CIs) were 1.1 (0.9, 1.2) in women and 0.9 (0.7, 1.2) in men. In women, the HR (CI) for exposure to a low cumulative DES dose was 1.2 (1.0, 1.4), and for DES exposure before 8 weeks' gestation was 1.2 (1.0, 1.4). In men, the HR for low dose was 1.2 (95% CI = 0.9, 1.6) and there was no association with timing. In women, associations were uninfluenced by the presence of DES-related vaginal epithelial changes or a prior diagnosis of DES-related adverse outcomes.
Conclusions: Prenatal DES exposure was not associated overall with risk of depression in women or men. In women, exposure in early gestation or to a low cumulative dose may be weakly associated with an increased depression risk.