High-Density Lipoprotein Function Is Reduced in Patients Affected by Genetic or Idiopathic Hypogonadism.

Abstract

CONTEXT:

Low testosterone levels are associated with an increased incidence of cardiovascular (CV) events, but the underlying biochemical mechanisms are not fully understood. The clinical condition of hypogonadism 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 (HDLs) may provide insights besides traditional risk factors.

DESIGN:

To determine whether reduced testosterone levels correlate with lipoprotein function, HDL cholesterol (HDL-C) efflux capacity (CEC) and serum cholesterol loading capacity (CLC).

PARTICIPANTS:

Genetic and idiopathic hypogonadal patients (n = 20) and control subjects (n = 17).

RESULTS:

Primary and secondary hypogonadal patients presented with lower 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 whole series, positive correlations between testosterone levels and both total HDL CEC (r2 = 0.359, P = 0.0001) and ABCG1 HDL CEC (r2 = 0.367, P = 0.0001) were observed. Conversely, serum CLC was markedly raised (+43%) in hypogonadals, increased, to a higher extent, in primary vs secondary hypogonadism (18.45 ± 2.78 vs 15.15 ± 2.10 µg cholesterol/mg protein) and inversely correlated with testosterone levels (r2 = 0.270, P = 0.001). HDL-C concentrations did not correlate with either testosterone levels, HDL CEC (total, ABCG1, and ABCA1) or serum CLC.

CONCLUSIONS:

In hypogonadal patients, proatherogenic lipoprotein-associated changes are associated with lower cholesterol efflux and increased influx, thus offering an explanation for a potentially increased CV risk.

• Authors: Maria Pia Adorni, Francesca Zimetti, Biagio Cangiano, Valeria Vezzoli, Franco Bernini, Donatella Caruso, Alberto Corsini, Cesare R Sirtori, Anna Cariboni, Marco Bonomi, Massimiliano Ruscica
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 104 Issue 8 Pg. 3097-3107 (08 01 2019) ISSN: 1945-7197 [Electronic] United States
• PMID: 30835274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Endocrine Society.

Chemical References

• ABCA1 protein, human
• ABCG1 protein, human
• ATP Binding Cassette Transporter 1
• ATP Binding Cassette Transporter, Subfamily G, Member 1
• Cholesterol, HDL
• Testosterone
• Cholesterol

Topics

• ATP Binding Cassette Transporter 1 (physiology)
• ATP Binding Cassette Transporter, Subfamily G, Member 1 (physiology)
• Adult
• Cardiovascular Diseases (etiology)
• Cholesterol (metabolism)
• Cholesterol, HDL (blood, physiology)
• Humans
• Hypogonadism (complications, metabolism)
• Male
• Middle Aged
• Testosterone (blood)