Wu Fredrick C W, von Eckardstein Arnold
Department of Endocrinology, Manchester Royal Infirmary, University of Manchester, Manchester M13 9WL, United Kingdom.
Endocr Rev. 2003 Apr;24(2):183-217. doi: 10.1210/er.2001-0025.
A significant and independent association between endogenous testosterone (T) levels and coronary events in men and women has not been confirmed in large prospective studies, although cross-sectional data have suggested coronary heart disease can be associated with low T in men. Hypoandrogenemia in men and hyperandrogenemia in women are associated with visceral obesity; insulin resistance; low high-density lipoprotein (HDL) cholesterol (HDL-C); and elevated triglycerides, low-density lipoprotein cholesterol, and plasminogen activator type 1. These gender differences and confounders render the precise role of endogenous T in atherosclerosis unclear. Observational studies do not support the hypothesis that dehydroepiandrosterone sulfate deficiency is a risk factor for coronary artery disease. The effects of exogenous T on cardiovascular mortality or morbidity have not been extensively investigated in prospective controlled studies; preliminary data suggest there may be short-term improvements in electrocardiographic changes in men with coronary artery disease. In the majority of animal experiments, exogenous T exerts either neutral or beneficial effects on the development of atherosclerosis. Exogenous androgens induce both apparently beneficial and deleterious effects on cardiovascular risk factors by decreasing serum levels of HDL-C, plasminogen activator type 1 (apparently deleterious), lipoprotein (a), fibrinogen, insulin, leptin, and visceral fat mass (apparently beneficial) in men as well as women. However, androgen-induced declines in circulating HDL-C should not automatically be assumed to be proatherogenic, because these declines may instead reflect accelerated reverse cholesterol transport. Supraphysiological concentrations of T stimulate vasorelaxation; but at physiological concentrations, beneficial, neutral, and detrimental effects on vascular reactivity have been observed. T exerts proatherogenic effects on macrophage function by facilitating the uptake of modified lipoproteins and an antiatherogenic effect by stimulating efflux of cellular cholesterol to HDL. In conclusion, the inconsistent data, which can only be partly explained by differences in dose and source of androgens, militate against a meaningful assessment of the net effect of T on atherosclerosis. Based on current evidence, the therapeutic use of T in men need not be restricted by concerns regarding cardiovascular side effects. Available data also do not justify the uncontrolled use of T or dehydroepiandrosterone for the prevention or treatment of coronary heart disease.
尽管横断面数据表明男性冠心病可能与低睾酮水平有关，但大型前瞻性研究尚未证实内源性睾酮（T）水平与男性和女性冠状动脉事件之间存在显著且独立的关联。男性雄激素缺乏和女性雄激素过多与内脏肥胖、胰岛素抵抗、低高密度脂蛋白（HDL）胆固醇（HDL-C）以及甘油三酯、低密度脂蛋白胆固醇和纤溶酶原激活物1升高有关。这些性别差异和混杂因素使得内源性睾酮在动脉粥样硬化中的精确作用尚不清楚。观察性研究不支持硫酸脱氢表雄酮缺乏是冠状动脉疾病危险因素这一假说。前瞻性对照研究尚未广泛调查外源性睾酮对心血管死亡率或发病率的影响；初步数据表明，冠状动脉疾病男性的心电图变化可能有短期改善。在大多数动物实验中，外源性睾酮对动脉粥样硬化的发展具有中性或有益作用。外源性雄激素对心血管危险因素具有明显有益和有害的双重影响，可降低男性和女性血清HDL-C、纤溶酶原激活物1（明显有害）、脂蛋白（a）、纤维蛋白原、胰岛素、瘦素和内脏脂肪量（明显有益）。然而，雄激素引起的循环HDL-C下降不应自动被认为具有促动脉粥样硬化作用，因为这些下降可能反而反映了胆固醇逆向转运加速。超生理浓度的睾酮刺激血管舒张；但在生理浓度下，已观察到对血管反应性有有益、中性和有害的影响。睾酮通过促进修饰脂蛋白的摄取对巨噬细胞功能产生促动脉粥样硬化作用，并通过刺激细胞胆固醇向HDL的流出产生抗动脉粥样硬化作用。总之，这些不一致的数据，只能部分地由雄激素剂量和来源的差异来解释，不利于对睾酮对动脉粥样硬化的净效应进行有意义的评估。根据目前的证据，男性使用睾酮治疗无需因担心心血管副作用而受到限制。现有数据也不能证明无节制地使用睾酮或脱氢表雄酮来预防或治疗冠心病是合理的。
