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

Reprod Toxicol. 2019 Mar;84:32-38. doi: 10.1016/j.reprotox.2018.12.008. Epub 2018 Dec 27.


Background: 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.

Methods: We assessed hormonally mediated outcomes in third generation women whose mothers were prenatally DES-exposed and unexposed.

Results: 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).

Conclusion: 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.

Keywords: DES; Diethylstilbestrol; Epigenetic; Granddaughters; Intergenerational; Third generation women.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Diethylstilbestrol / toxicity*
  • Endocrine Disruptors / toxicity*
  • Female
  • Humans
  • Maternal-Fetal Exchange
  • Menstruation Disturbances / epidemiology*
  • Mothers
  • National Cancer Institute (U.S.)
  • Pregnancy
  • Premature Birth / epidemiology*
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Reproduction
  • Risk
  • United States
  • Young Adult


  • Endocrine Disruptors
  • Diethylstilbestrol