Anthropometric biomarkers for abnormal prenatal reproductive hormone exposure in women with Mayer-Rokitanksy-Küster-Hauser syndrome, polycystic ovary syndrome, and endometriosis

Objective: To study whether markers of prenatal exposure to reproductive hormones are related to Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, polycystic ovary syndrome (PCOS), and endometriosis. Design: Case-control study. Comparison of sex hormone-related external genital and digital characteristics in cases and controls. Setting: University hospital. Patient(s): We enrolled 172 women in four groups—women with MKRH, women with PCOS, women with endometriosis, and controls (43 in each group). Intervention(s): Measurement of two anthropometric biomarkers: anogenital distance and digit ratio. Main Outcome Measure(s): Anogenital distance was measured from the anus to the anterior clitoral surface (AGDac) and from the anus to the posterior fourchette (AGDaf). For the digit ratio we used a direct, as well as a computer-assisted graphic measurement to measure the length of the second and fourth digit. Result(s): After adjustment for body mass index and age, AGDac was the shortest in endometriosis and the longest in PCOS groups, with a mean difference of 10 mm (95% confidence interval 3.1–16.8). AGDaf but not AGDac measures were found to be significantly larger in the MRKH group, with a mean difference compared with controls of 2.6 mm (95% confidence interval 0.1–5.2). The digit ratio was not significantly different between the groups. Conclusion(s): In this study we did find limited evidence for androgen exposure during the development of MRKH. This is compatible with the hypothesis that the uterovaginal agenesis may have been the result of temporary prenatal exposure to altered gonadal hormone concentrations. For endometriosis and PCOS we confirm previously observed associations for anogenital distance reflecting possible estrogen-based and androgen-based intrauterine origins, respectively. Dutch Trial Registration Number: NTR7492.