title: Hypospadias in sons of women exposed to diethylstilbestrol in utero: a cohort study.
abstract: BACKGROUND
  Transgenerational effects of diethylstilbestrol (DES) have been reported in animals, but effects in human beings are unknown. Alerted by two case reports, we aimed to establish the risk of hypospadias in the sons of women who were exposed to DES in utero.
  
  
  METHODS
  We did a cohort study of all sons of a Dutch cohort of 16284 women with a diagnosis of fertility problems. We used a mailed questionnaire assessing late effects of fertility treatment to identify boys with hypospadias. We compared the prevalence rate of hypospadias between boys with and without maternal DES exposure in utero.
  
  
  RESULTS
  16284 mothers (response rate 67%) reported 8934 sons. The mothers of 205 boys reported DES exposure in utero. Four of these children were reported to have hypospadias. In the remaining 8729 children, only eight cases of hypospadias were reported (prevalence ratio 21.3 [95% CI 6.5-70.1]). All cases of hypospadias were medically confirmed. Maternal age or fertility treatment did not affect the risk of hypospadias. Children conceived after assisted reproductive techniques such as in-vitro fertilisation were not at increased risk of hypospadias compared with children conceived naturally (1.8, 0.6-5.7).
  
  
  CONCLUSIONS
  Our findings suggest an increased risk of hypospadias in the sons of women exposed to DES in utero. Although the absolute risk of this anomaly is small, this transgenerational effect of DES warrants additional studies.
authors.affiliation: Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Helen
authors.initials: H
authors.lastname: Klip
authors.forename: Janneke
authors.initials: J
authors.lastname: Verloop
authors.forename: Jan D
authors.initials: JD
authors.lastname: van Gool
authors.forename: Marlies E T A
authors.initials: ME
authors.lastname: Koster
authors.forename: Curt W
authors.initials: CW
authors.lastname: Burger
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
mesh_terms: D015331:Cohort Studies; D016001:Confidence Intervals; D004054:Diethylstilbestrol / Q000009:adverse effects*; D004968:Estrogens, Non-Steroidal / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007021:Hypospadias / Q000139:chemically induced* / Q000453:epidemiology; D007231:Infant, Newborn; D007247:Infertility, Female / Q000628:therapy; D008297:Male; D018811:Maternal Exposure / Q000706:statistics & numerical data; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015995:Prevalence; D012307:Risk Factors
chemical_list: D004968:Estrogens, Non-Steroidal; D004054:Diethylstilbestrol