Male subclinical hypogonadism and late-onset hypergonadotrophic hypogonadism: mechanisms, endothelial function, and interplay between reproductive hormones, undercarboxylated osteocalcin, and endothelial dysfunction

Abstract

Background Pathogenesis and endothelial function in subclinical hypogonadism (SCH) remain unclear. Undercarboxylated osteocalcin (ucOC) participates in atherosclerosis and reproduction. We explored the underlying mechanisms and interplay of endothelial dysfunction, unOC and reproductive hormones in SCH and primary late-onset hypogonadism (LOH). Methods In the SCH, LOH, and healthy eugonadal male groups, we measured serum unOC, calculated luteinizing hormone/testosterone (LH/T), LH.T product, and estradiol/T (E/T) as indicators of impaired Leydig cells, androgen sensitivity index (ASI), and aromatase activity, respectively (LH set-point regulators), and assessed flow-mediated dilation of the brachial artery (FMD%), carotid-intima media thickness (CIMT), and aortic stiffness (AS). Results ↑LH/T, ↑ASI, ↓aromatase activity, normal T, follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) levels, ↑unOC, and enhanced atherosclerotic markers (↓FMD%, ↑CIMT, ↑AS) are characteristics of SCH. Testosterone was positively correlated with FMD% in SCH. The independent predictors were: SHBG and LH for FMD% and CIMT, respectively, and LH/T, ucOC, FSH, estradiol, and E/T ratio for AS in the LOH group; and LH for FMD% & AS and LH and LH/T for CIMT in all study subjects. Conclusions SCH is a distinct clinical entity characterized by impaired androgen sensitivity and aromatase activity, compensatory elevated unOC, endothelial dysfunction, and anti-atherogenic role of testosterone.