Fetal genital effects of first-trimester sex hormone exposure: a meta-analysis

Obstet Gynecol. 1995 Jan;85(1):141-9. doi: 10.1016/0029-7844(94)00341-a.


Objective: To determine if first-trimester exposure to sex hormones, and oral contraceptives (OCs) specifically, is associated with an increased risk of external fetal genital malformations.

Data sources: MEDLINE and Science Citation Index data bases were searched for the years 1966-1992 for relevant English-language articles on first-trimester sex-hormone exposure and fetal genital changes.

Methods of study selection: One hundred eighty-six articles were identified initially. Inclusion criteria were cohort or case-control studies, first-trimester sex-hormone exposure, and live infants or full-term stillborn infants with external genital malformations. Exclusion criteria were diethylstilbestrol exposure, spontaneous abortions, and teratogen exposure.

Data extraction and synthesis: The Methods section of each study was reviewed independently by two authors and two outside reviewers, using the above criteria. Fourteen studies, seven cohort and seven case-control, involving 65,567 women, met the criteria for meta-analysis. Extracted data were entered into 2 x 2 tables. The overall summary odds ratio (OR) was 1.09 (95% confidence interval [CI] 0.90-1.32); subanalysis of OC exposure identified an OR of 0.98 (95% CI 0.24-3.94).

Conclusion: There was no association between first-trimester exposure to sex hormones generally (or to OCs specifically) and external genital malformations. Thus, women exposed to sex hormones after conception may be assured there is no increased risk of fetal sexual malformation.

Publication types

  • Meta-Analysis

MeSH terms

  • Case-Control Studies
  • Cohort Studies
  • Confidence Intervals
  • Contraceptives, Oral / adverse effects
  • Female
  • Fetal Diseases / chemically induced*
  • Fetal Diseases / epidemiology
  • Genitalia, Female / abnormalities
  • Genitalia, Female / drug effects*
  • Genitalia, Male / abnormalities
  • Genitalia, Male / drug effects*
  • Gonadal Steroid Hormones / adverse effects*
  • Humans
  • Male
  • Odds Ratio
  • Pregnancy
  • Pregnancy Trimester, First / drug effects
  • Retrospective Studies
  • Risk Factors


  • Contraceptives, Oral
  • Gonadal Steroid Hormones