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

Lalitha Raman-Wilms, Alice Linin Tseng, Suzanne Wighardt, Thomas R. Einarson, Gideon Koren

Research output: Contribution to journalReview articlepeer-review

172 Scopus citations

Abstract

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 × 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 firsttrimester 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.

Original languageEnglish
Pages (from-to)141-149
Number of pages9
JournalObstetrics and Gynecology
Volume85
Issue number1
DOIs
StatePublished - Jan 1995
Externally publishedYes

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