title: Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES).
abstract: 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.
authors.affiliation: Department of Community and Family Medicine, Dartmouth Medical School, and the Norris Cotton Cancer Center, Lebanon, NH 03756, USA. Linda.Titus-Ernstoff@Dartmouth.edu
authors.forename: Linda
authors.initials: L
authors.lastname: Titus-Ernstoff
authors.forename: Rebecca
authors.initials: R
authors.lastname: Troisi
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Hatch
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Wise
authors.forename: Julie
authors.initials: J
authors.lastname: Palmer
authors.forename: Marianne
authors.initials: M
authors.lastname: Hyer
authors.forename: Raymond
authors.initials: R
authors.lastname: Kaufman
authors.forename: Ervin
authors.initials: E
authors.lastname: Adam
authors.forename: William
authors.initials: W
authors.lastname: Strohsnitter
authors.forename: Kenneth
authors.initials: K
authors.lastname: Noller
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Herbst
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gibson-Chambers
authors.forename: Patricia
authors.initials: P
authors.lastname: Hartge
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hoover
mesh_terms: D000328:Adult; D004054:Diethylstilbestrol / Q000009:adverse effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D045166:Estradiol Congeners / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000139:chemically induced; D018811:Maternal Exposure; D008599:Menstruation Disturbances / Q000139:chemically induced*; D016017:Odds Ratio; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016016:Proportional Hazards Models; D012306:Risk
chemical_list: D045166:Estradiol Congeners; D004054:Diethylstilbestrol