Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES)

• Published in: International journal of epidemiology Vol. 35; no. 4; pp. 862 - 868
• Main Authors: Titus-Ernstoff, Linda, Troisi, Rebecca, Hatch, Elizabeth E, Wise, Lauren A, Palmer, Julie, Hyer, Marianne, Kaufman, Raymond, Adam, Ervin, Strohsnitter, William, Noller, Kenneth, Herbst, Arthur L, Gibson-Chambers, Jennifer, Hartge, Patricia, Hoover, Robert N
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2006; Oxford Publishing Limited (England)
• Subjects: Adult; Diethylstilbestrol; Diethylstilbestrol - adverse effects; Epigenesis, Genetic - drug effects; epigenetic alternations; Estradiol Congeners - adverse effects; Female; Humans; infertility; Infertility, Female - chemically induced; Maternal Exposure; menstruation; Menstruation Disturbances - chemically induced; Odds Ratio; Pregnancy; prenatal exposure; Prenatal Exposure Delayed Effects; Proportional Hazards Models; reproductive histories; Risk
• ISSN: 0300-5771; 1464-3685
• DOI: 10.1093/ije/dyl106

Background In women, prenatal exposure to diethylstilbestrol (DES) is associated with adult reproductive dysfunction. The mouse model, which replicates many DES outcomes, suggests DES causes epigenetic alterations, which are transmissable to daughters of prenatally exposed animals. We report menstrual and reproductive characteristics in a unique cohort comprising daughters of women exposed prenatally to DES. Methods Menstrual and reproductive outcomes and baseline characteristics were assessed by mailed questionnaire in 793 women whose mothers had documented information regarding in utero DES exposure. Results Mean age at menarche was 12.6 years in both groups, but daughters of the exposed women attained menstrual regularization later (mean age of 16.2 years vs. 15.8 years; P = 0.05), and were more likely to report irregular menstrual periods, odds ratio (OR) = 1.54 [95% confidence interval (95% CI 1.02–2.32)]. A possible association between mothers' DES exposure and daughters' infertility was compatible with chance, age, and cohort adjusted OR = 2.19 (95% CI 0.95–5.07). We found limited evidence that daughters of the exposed had more adverse reproductive outcomes, but daughters of exposed women had fewer live births (1.6) than the unexposed (1.9) (P = 0.005). Conclusions The high risk of reproductive dysfunction seen in women exposed to DES in utero was not observed in their daughters, but most women in our cohort have not yet attempted to start their families, and further follow-up is needed to assess their reproductive health. Our findings of menstrual irregularity and possible infertility in third-generation women are preliminary but compatible with speculation regarding transgenerational transmission of DES-related epigenetic alterations in humans.