Estrogen Metabolism in Postmenopausal Women Exposed In Utero to Diethylstilbestrol

Background: Prenatal diethylstilbestrol (DES) exposure is associated with adverse reproductive outcomes and cancer of the breast and vagina/cervix in adult women. DES effects on estrogen metabolism have been hypothesized, but reproductive hormone concentrations and metabolic pathways have not been comprehensively described. Methods: Blood samples were provided by 60 postmenopausal women (40 exposed and 20 unexposed) who were participants in the NCI Combined DES Cohort Study, had never used hormone supplements or been diagnosed with cancer, had responded to the most recent cohort study questionnaire, and lived within driving distance of Boston University Medical School (Boston, MA). Parent estrogens and their metabolites were measured by high-performance liquid chromatography-tandem mass spectrometry. Age-adjusted percent changes in geometric means and associated 95% confidence intervals (CIs) between the exposed and unexposed were calculated. Results: Concentrations of total estrogens (15.3%; CI, -4.1-38.5) and parent estrogens (27.1%; CI, -8.2-76.1) were slightly higher in the DES-exposed than unexposed. Ratios of path2:parent estrogens (-36.5%; CI, -53.0 to -14.3) and path2:path16 (-28.8%; CI, -47.3-3.7) were lower in the DES exposed. These associations persisted with adjustment for total estrogen, years since menopause, body mass index, parity, and recent alcohol intake. Conclusions: These preliminary data suggest that postmenopausal women who were prenatally DES exposed may have relatively less 2 than 16 pathway estrogen metabolism compared with unexposed women. Impact: Lower 2 pathway metabolism has been associated with increased postmenopausal breast cancer risk and could potentially offer a partial explanation for the modest increased risk observed for prenatally DES-exposed women. (C) 2018 AACR.