Background: Male hypogonadism is known to be associated with an increased incidence of cardiovascular (CV) events, although the underlying biochemical mechanisms are so far not fully understood. The clinical condition characterized by low levels of testosterone offers a unique model to unravel the possible role of lipoprotein-associated abnormalities in CV risk. In particular, the assessment of the functional capacities of high-density lipoproteins (HDL) may provide novel insights besides traditional risk factors.
Aim of the study: Aim of our study was to determine whether male hypogonadal patients have an impaired function of serum lipoproteins and if testosterone levels correlate with this function.
Methods: We evaluated HDL cholesterol efflux capacity (CEC, both ATP-binding cassette transporter and aqueous diffusion-mediated) and serum cholesterol loading capacity (CLC) in a series of 20 hypogonadal patients and in 17 age and body mass index (BMI) matched healthy control subjects.
Results: Hypogonadism significantly reduced the HDL ATP-binding cassette transporter A1 (ABCA1)-, ATP binding cassette transporter G1 (ABCG1) - and aqueous diffusion-mediated CEC (−19.6%, −40.9% and −12.9%, respectively), with a 16.2% decrement of total CEC. In the entire cohort, positive correlations between testosterone levels and both total HDL CEC (r2=0.359, P=0.0001) and ABCG1 HDL CEC (r2=0.367, P=0.0002) were observed. On the contrary, serum CLC, significantly raised (+43%) in hypogonadal patients, was inversely correlated with testosterone levels (r2=0.270, P=0.00014). HDL-C concentrations did not correlate with either testosterone levels, HDL CECs or serum CLC.
Conclusions: Our results show that in hypogonadal patients pro-atherogenic lipoprotein-associated changes lead to reduced cholesterol efflux and increased influx, thus suggesting a potential explanation for the increased CV risk in hypogonadal patients and a possible objective functional parameter of hormonal dysfunction.
18 - 21 May 2019
European Society of Endocrinology