Reproductive and hormone-related outcomes in women whose mothers were exposed in utero to diethylstilbestrol (DES): A report from the US National Cancer Institute DES Third Generation Study

Diagram showing Third Generation Study women in the present analysis (dark gray). [Display omitted] •Studies of mice indicate intergenerational effects of DES exposure; i.e., effects in the offspring of prenatally DES-exposed animals.•We assessed DES exposure in relation to outcomes in a cohort of third generation women whose mothers were prenatally DES-exposed and unexposed.•Results suggested DES-exposed third generation women have increased risks of menstrual aberrations, preterm birth, and possibly ectopic pregnancy.•The data did not indicate an increase in same-sex orientation in DES-exposed third generation women.•Menstrual aberration and preterm birth in the DES-exposed third generation suggest intergenerational effects of endocrine disrupting chemicals in humans. Animal studies suggest that prenatal exposure to diethylstilbestrol (DES) causes epigenetic alterations in primordial germ cells that affect the next generation, but human studies are sparse. We assessed hormonally mediated outcomes in third generation women whose mothers were prenatally DES-exposed and unexposed. Compared to the unexposed, DES-exposed third generation women had an increased risk of irregular menses and amenorrhea; the respective prevalence ratios and 95% confidence intervals (CI) in follow-up data were 1.32 (95% CI: 1.10, 1.60) and 1.26 (95% CI: 1.06, 1.49); associations were more apparent in third generation women whose prenatally DES-exposed mothers were affected by vaginal epithelial changes. The follow-up data also indicated an association with preterm delivery (relative risk (RR): 1.54; 95% CI: 1.35, 1.75). DES third generation women may have an increased risk of irregular menstrual cycles, amenorrhea, and preterm delivery, consistent with inter-generational effects of endocrine disrupting chemical exposure in humans.