This thesis provides the first description of circulating anti-Müllerian hormone (AMH) in older men. AMH is a gonadal hormone, with overt function in the generation of the male phenotype during development, and a biomarker for ovarian reserve in women. AMH is one of four circulating hormones produced by the adult testes, and assumed to have no functional significance in men. Therefore there is an absence of information regarding basic physiology of AMH in the blood of men. This thesis posits that AMH may have cryptic functions, with putative interactions to the other testicular hormones. AMH also belong to the TGF superfamily of cytokines with ubiquitous roles and convergent intracellular signalling in a contexual manner. The role of AMH may become more evident in a model of dysregulated homeostasis, such as that seen with ageing and frailty. This PhD examined a local cohort of 223 men from 19 years to 90 years old for their circulating AMH levels. Three testicular hormones were concurrently examined for interactions with AMH; Inhibin B (InhB), testosterone, and insulin-like peptide 3 (INSL3). The serum profiles of these four hormones were examined throughout the day, and across the age spectrum with a focus on men aged 70 years and older. A small group of older women were also examined for their circulating AMH level to determine for sexual dimorphism with ageing. The extent of cleavage of AMH precursor protein was also studied, and compared between men and boys. A pilot study was concurrently set up to test for the feasibility of correlating AMH and other hormones to functional traits associated with ageing. In healthy young men, circulating AMH and INSL3 levels were both stable throughout the day and independent to each other. This contrasted to the overt diurnal pattern exhibited by testosterone and InhB. Circulating AMH level varies significantly between men, with age-related decline. AMH level was partially correlated to the other Sertoli hormone InhB which became divergent in older men. These findings were concordant with examination of a distinct cohort of older men in the North Island of New Zealand. Both cohorts however had average circulating AMH levels which were lower than a third age-matched cohort of age with healthy cardiovascular status. Circulating AMH was largely sexually dimorphic with ageing, but not invariantly. A minority of older men lacked AMH like all older women. All four circulating testicular hormones are independent in younger men. All four testicular hormones exhibits age-related decline, resulting in multiple combinations of testicular hormonal deficiencies. A minority of older men was deficient in all testicular hormones, similar to all postmenopausal women. The precursor hormone of AMH in blood was strongly linked to its total AMH level. However the extent of its cleavage was distinct to the circulating AMH concentration, and also to the other testicular hormones. AMH was cleaved more in both younger and older men, when compared to boys, with no overlap in their ranges. Amongst men over 70 years, circulating AMH showed a relationship to cognitive function that was highly statistically significant. This was independent to the other testicular hormones. The extent of its cleavage correlated to physical function and weight. AMH is present in the circulation in men, including the oldest old. AMH may play a role as a chronic reporter about the state of the testes that is independent to the other three testicular hormones. This has relevance to the understanding of hypogonadism in the older male.
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Circulating anti-Müllerian hormone in the older man
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