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

Anogenital distance is a well-validated marker of prenatal testosterone, with shorter distances indicating lower levels during early gestation. A suite of studies has tested for links of anogenital distance with risk of endometriosis, but the findings are variable, leading to uncertainty in interpretation. This study was conducted to provide an overall statistical assessment of whether anogenital distance is altered in women with endometriosis, compared to controls. A systematic review and meta-analysis were 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. Meta-analysis showed that shorter 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, the association for anogenital distance AC, measured from the anus to the clitoral surface, was non-significant. Both analyses demonstrated significant heterogeneity across studies. Too few studies were available for robust investigation of publication bias. The 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 conclusion has implications for understanding the causes and treatment of endometriosis.