Hypospadias in sons of women exposed to diethylstilbestrol in utero

Epidemiology. 2005 Jul;16(4):583-6. doi: 10.1097/01.ede.0000164789.59728.6d.


Background: Diethylstilbestrol (DES) is a synthetic estrogen that was widely prescribed to pregnant women before 1971. DES increases the risk of breast cancer in women who took the drug and the risk of reproductive tract abnormalities in their offspring. Dutch investigators have reported a 20-fold increase in risk of hypospadias among sons of women who were exposed to DES in utero. We assessed this relation in data from an ongoing study of DES-exposed persons.

Methods: Several U.S. cohorts of women with documented exposure in utero to DES have been followed by mailed questionnaires since the 1970s. Comparison subjects are unexposed women of the same ages. In 1997, participants were asked about congenital abnormalities in their children. We calculated prevalence odds ratios for the risk of hypospadias in sons of exposed mothers relative to sons of unexposed mothers using generalized estimating equations to adjust for multiple sons per mother and controlling for maternal age at the son's birth.

Results: We obtained data from 3916 exposed and 1746 unexposed women. These women reported a total of 13 liveborn sons with hypospadias (10 exposed, 3 unexposed). The prevalence odds ratio for risk of hypospadias among the exposed was 1.7 (95% confidence interval = 0.4-6.8).

Conclusions: Our findings do not support a greatly increased risk of hypospadias among the sons of women exposed to DES in utero, as has been previously reported.

Publication types

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

MeSH terms

  • Diethylstilbestrol / toxicity*
  • Estrogens, Non-Steroidal / toxicity*
  • Female
  • Follow-Up Studies
  • Humans
  • Hypospadias / chemically induced*
  • Hypospadias / epidemiology
  • Male
  • Maternal Exposure / adverse effects*
  • Nuclear Family
  • Odds Ratio
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / epidemiology
  • Surveys and Questionnaires
  • United States / epidemiology


  • Estrogens, Non-Steroidal
  • Diethylstilbestrol