Male Subclinical Hypogonadism: Mechanisms with Interplay of Reproductive Hormones, Undercarboxylated Osteocalcin and Endothelial Dysfunction
Abstract BackgroundPathogenesis and endothelial function in subclinical hypogonadism (SCH) are unknown. Undercarboxylated osteocalcin (ucOC) participate in atherosclerosis and reproduction. We studied interplay of endothelial function, unOC and reproductive hormones with SCH.Methodsamong SCH, late onset hypogonadism (LOH), and healthy eugonadal male (HC) groups, we measured sex hormones and unOC, calculated luteinizing hormone/testosterone (LH/T), LH.T product and estradiol/T (E/T) as indicators of impaired leydig cell, androgen sensitivity index (ASI) & aromatase activity respectively and regulators for LH set point. We assessed flow mediated dilation of brachial artery (FMD%), carotid- intima media thickness (CIMT) and aortic stiffness index (AS) as markers of subclinical atherosclerosis.ResultsContrary to LOH, SCH had higher ASI, lower E/T ratio& similar T, follicle stimulating hormone and sex hormone binding globulin (SHBG) compared to HC, LH/ T was significant higher in LOH and lower in HC than SCH . Similar to LOH, SCH had significant lower FMD% and higher CIMT, AS, unOC & inflammatory marker and atherogenic lipid profile than HC. LH, LH/T & ucOC negatively while T positively FMD% meanwhile. LH, LH/T & ucOC positively while testosterone negatively correlated with CIMT. LH and LH/T positively while estradiol and E/T negatively related to AS. ucOC positively correlated to LH, LH/T, E SHBG & negatively correlated with T. Independent predictors were LH for FMD% & AS meanwhile LH and LH/T for CIMT.ConclusionsSCH as not impaired testicular function state is characterized by androgen insensitivity, impaired aromatase activity, compensatory elevated unOC and atherogenic role of LH in endothelial dysfunction.