Department of Food and Drug, University of Parma, Parma, Italy.
Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy.
J Clin Endocrinol Metab. 2019 Aug 1;104(8):3097-3107. doi: 10.1210/jc.2018-02027.
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.
To determine whether reduced testosterone levels correlate with lipoprotein function, HDL cholesterol (HDL-C) efflux capacity (CEC) and serum cholesterol loading capacity (CLC).
Genetic and idiopathic hypogonadal patients (n = 20) and control subjects (n = 17).
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.
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.
低睾酮水平与心血管（CV）事件的发生率增加有关，但潜在的生化机制尚不完全清楚。低睾丸激素症的临床状况提供了一个独特的模型，可以揭示脂蛋白相关异常在 CV 风险中的可能作用。特别是，评估高密度脂蛋白（HDL）的功能能力可能会提供除传统危险因素以外的见解。
为了确定降低的睾酮水平是否与脂蛋白功能相关，评估了 HDL 胆固醇（HDL-C）流出能力（CEC）和血清胆固醇负荷能力（CLC）。
遗传性和特发性低睾丸激素症患者（n=20）和对照组（n=17）。
原发性和继发性低睾丸激素症患者的 HDL 三磷酸腺苷结合盒转运体 A1（ABCA1）-、三磷酸腺苷结合盒转运体 G1（ABCG1）-和水扩散介导的 CEC 分别降低了 19.6%、40.9%和 12.9%，总 CEC 降低了 16.2%。在整个系列中，观察到睾酮水平与总 HDL CEC（r2=0.359，P=0.0001）和 ABCG1 HDL CEC（r2=0.367，P=0.0001）之间呈正相关。相反，低睾丸激素症患者的血清 CLC 明显升高（+43%），原发性低睾丸激素症患者的升高程度更高（18.45±2.78 vs 15.15±2.10 µg 胆固醇/mg 蛋白），与睾酮水平呈负相关（r2=0.270，P=0.001）。HDL-C 浓度与睾酮水平、HDL CEC（总、ABCG1 和 ABCA1）或血清 CLC 均无相关性。
在低睾丸激素症患者中，动脉粥样硬化脂蛋白相关变化与胆固醇流出减少和流入增加有关，从而为潜在的 CV 风险增加提供了解释。
