Relative levels of the proprotein and cleavage‐activated form of circulating human anti‐Müllerian hormone are sexually dimorphic and variable during the life cycle

Anti‐Müllerian hormone (AMH) is a gonadal hormone, which induces aspects of the male phenotype, and influences ovarian follicular recruitment. AMH is synthesized as a proprotein (proAMH), which is incompletely cleaved to the receptor‐competent AMH(N) (,C). AMH ELISAs have not distinguished between proAMH and AMH(N) (,C); consequently, the physiological ranges of circulating proAMH and AMH(N) (,C) are unknown. A novel proAMH ELISA has been used to assay serum proAMH in humans. Total AMH was also measured, enabling the AMH(N) (,C) concentration to be calculated. Stored serum from 131 boys, 80 younger, and 106 older men were examined, with serum from 14 girls and 18 women included for comparison. The mean levels of proAMH and AMH(N) (,C) in pM were respectively: boys (253, 526), men (7.7, 36), elderly men (5.7, 19), girls (3.3, 15), and women (5.2, 27) (boys vs. men, P < 0.001; girls vs. women, P = 0.032). The proportion of proAMH as a percentage of total AMH (API) was approximately twofold higher in boys than men (P < 0.001) with little overlap between the ranges, with girls also exhibiting lesser cleavage of their AMH than women (P < 0.001). The API varied within each population group. In young men, the API did not correlate with circulating levels of the other testicular hormones (testosterone, InhB, and INSL3). In conclusion, the cleavage of circulating AMH varies extensively within the human population, with most individuals having significant levels of proAMH. The physiological and clinical relevance of circulating proAMH needs to be established.