Anogenital Distance and Prenatal Androgen Exposure in Female Fetus and Newborns: A Systematic Review

Abstract

The aim of this systematic review is to examine the relationship between anogenital distance (AGD) and prenatal androgen exposure in female offspring, and to assess whether there is sufficient scientific evidence that AGD could be a biomarker of in utero exposure in girls. A systematic approach was adopted to the screening and selection of the studies through Pub Med database. 959 documents were found in Pub Med search, 919 of them were excluded for lack of relevance, and 40 studies were included in the review. A significant portion of the selected studies (25 papers) focuses on the effect of exposure to endocrine disrupting agents (EDAs) such as phthalates, bisphenol A, and perfluoroalkyl substances. The other exposure factors examined in the studies are polycystic ovary syndrome, smoking and alcohol use, and maternal stressful life events. In 19 studies, a significant association has been reported between prenatal exposure factors and AGD length in female fetus and newborns. In the remaining 21 studies, no significant association was found. In conclusion, although there is still no a clear and conclusive evidence, a growing body of research provides data supporting that AGD may be considered a reliable marker of in utero androgen exposure in female infants. Our review highlights significant knowledge gaps with regard to some androgen or anti-androgen exposure factors. Much more research needed to understand the relationship of anogenital distance with in utero hormonal milieu and offspring’s reproductive system development.