title: Adverse health outcomes in women exposed in utero to diethylstilbestrol.
abstract: BACKGROUND
  Before 1971, several million women were exposed in utero to diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood.
  
  
  METHODS
  We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls. We assessed the risks of 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero.
  
  
  RESULTS
  Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows: for infertility, 33.3% vs. 15.5% (hazard ratio, 2.37; 95% confidence interval [CI], 2.05 to 2.75); spontaneous abortion, 50.3% vs. 38.6% (hazard ratio, 1.64; 95% CI, 1.42 to 1.88); preterm delivery, 53.3% vs. 17.8% (hazard ratio, 4.68; 95% CI, 3.74 to 5.86); loss of second-trimester pregnancy, 16.4% vs. 1.7% (hazard ratio, 3.77; 95% CI, 2.56 to 5.54); ectopic pregnancy, 14.6% vs. 2.9% (hazard ratio, 3.72; 95% CI, 2.58 to 5.38); preeclampsia, 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI, 1.07 to 1.89); stillbirth, 8.9% vs. 2.6% (hazard ratio, 2.45; 95% CI, 1.33 to 4.54); early menopause, 5.1% vs. 1.7% (hazard ratio, 2.35; 95% CI, 1.67 to 3.31); grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4% (hazard ratio, 2.28; 95% CI, 1.59 to 3.27); and breast cancer at 40 years of age or older, 3.9% vs. 2.2% (hazard ratio, 1.82; 95% CI, 1.04 to 3.18). For most outcomes, the risks among exposed women were higher for those with vaginal epithelial changes than for those without such changes.
  
  
  CONCLUSIONS
  In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes. (Funded by the National Cancer Institute.).
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. hooverr@mail.nih.gov
authors: Robert N
authors: RN
authors: Hoover
authors: Marianne
authors: M
authors: Hyer
authors: Ruth M
authors: RM
authors: Pfeiffer
authors: Ervin
authors: E
authors: Adam
authors: Brian
authors: B
authors: Bond
authors: Andrea L
authors: AL
authors: Cheville
authors: Theodore
authors: T
authors: Colton
authors: Patricia
authors: P
authors: Hartge
authors: Elizabeth E
authors: EE
authors: Hatch
authors: Arthur L
authors: AL
authors: Herbst
authors: Beth Y
authors: BY
authors: Karlan
authors: Raymond
authors: R
authors: Kaufman
authors: Kenneth L
authors: KL
authors: Noller
authors: Julie R
authors: JR
authors: Palmer
authors: Stanley J
authors: SJ
authors: Robboy
authors: Robert C
authors: RC
authors: Saal
authors: William
authors: W
authors: Strohsnitter
authors: Linda
authors: L
authors: Titus-Ernstoff
authors: Rebecca
authors: R
authors: Troisi
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000139:chemically induced; D001943:Breast Neoplasms / Q000139:chemically induced*; D004054:Diethylstilbestrol / Q000009:adverse effects*; D004968:Estrogens, Non-Steroidal / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D005833:Genital Neoplasms, Female / Q000139:chemically induced*; D006801:Humans; D008594:Menopause, Premature; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced*; D011297:Prenatal Exposure Delayed Effects; D050497:Stillbirth; D002578:Uterine Cervical Dysplasia / Q000139:chemically induced
chemical_list: D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol