ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 GP69 | DOI: 10.1530/endoabs.63.GP69

Male patients with hypogonadism have an impaired lipoprotein function

Biagio Cangiano1,2, Maria Pia Adorni3, Francesca Zimetti3, Valeria Vezzoli2, Franco Bernini3, Donatella Caruso4, Alberto Corsini4,5, Cesare R. Sirtori6, Anna Cariboni4, Massimiliano Ruscica4 & Marco Bonomi1,2

1Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; 2IRCCS Istituto Auxologico Italiano, Division of Endocrine and Metabolic Diseases & Lab. of Endocrine and Metabolic Research, Milan, Italy; 3Department of Food and Drug, University of Parma, Parma, Italy; 4Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; 5Multimedica IRCCS, Milan, Italy; 6Centro Dislipidemie, A.S.S.T. Grande Ospedale Metropolitano Niguarda, Milan, Italy.

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.