Efficacy of predictive models for polycystic ovary syndrome using serum levels of two antimüllerian hormone isoforms (proAMH and AMH_N,C)

Objective To compare total antimüllerian hormone (AMH), proAMH, AMH_N,C, and the ratio of the two forms in predictive models for polycystic ovary syndrome (PCOS) diagnosis. Total AMH consists of proAMH (inactive precursor) and AMH_N,C (receptor-competent), but neither isoform has been tested individually for their ability to predict PCOS diagnosis. Design Cross-sectional study using biobanked samples collected between July 2008 and January 2010. Setting Not applicable. Patient(s) Overweight, premenopausal women aged 18–45 years with PCOS (n = 45, with 21 fulfilling National Institutes of Health diagnostic criteria and 24 fulfilling European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE) criteria, but not National Institutes of Health criteria) and without PCOS (n = 23 controls). Intervention(s) None. Main Outcome Measure(s) Serum concentrations of proAMH and total AMH (proAMH and AMH_N,C combined) were determined by immunoassay. The AMH_N,C concentrations were calculated by subtraction ([AMH_N,C] = [total AMH] – [proAMH]). Relative levels of proAMH were expressed as the AMH prohormone index (API = [ProAMH]/[Total AMH] × 100). Result(s) In women with PCOS, total AMH, proAMH, and AMH_N,C levels were higher, and the API was lower (P=.010), than in controls indicating increased conversion of proAMH to AMH_N,C. Receiver-operating characteristic analysis for proAMH (area under the curve [AUC] = 0.82), AMH_N,C (AUC = 0.86), and API (AUC = 0.70) did not improve the prediction for PCOS when compared with total AMH (AUC = 0.86). Conclusion(s) The proAMH and AMH_N,C do not appear to improve the ability to predict a diagnosis of PCOS beyond total AMH assays. However, the ratio of inactive proAMH precursor to receptor-competent AMH_N,C (API) differs in women with PCOS relative to unaffected controls indicating that AMH signaling mechanisms may be altered in women with PCOS.