Endometriosis risk is associated with shorter anogenital distance by meta-analysis

Abstract

AbstractBackgroundAnogenital distance is a well-validated marker of prenatal testosterone, with shorter distances indicating lower levels during early gestation. A suite of studies has linked anogenital distance with risk of endometriosis, but the findings are variable, leading to uncertainty in interpretation. The relationship of anogenital distance with endometriosis is especially important because lower testosterone has been associated with endometriosis in recent Mendelian Randomization studies, which implies causality in the association, with direct implications for future research and treatment.MethodsA systematic review and meta-analysis was conducted on the association of endometriosis with anogenital distance. Three databases were queried in the identification phase, and a random-effects meta-analysis was applied to the data in studies that met the inclusion criteria.ResultsShorter anogenital distance AF, measured from the anus to the posterior fourchette, was significantly associated with higher risk of endometriosis in the meta-analysis. By contrast, there was no such association for anogenital distance AC, measured from the anus to the clitoral surface. Both analyses demonstrated significant heterogeneity across studies. Too few studies were available for robust investigation of publication bias.ConclusionsThe association of short anogenital distance with endometriosis risk provides support for the hypothesis that endometriosis represents, in part, a disorder mediated by relatively low testosterone levels in early prenatal development. This conclusions has notable implications for understanding the causes and treatment of endometriosis.