Eckardstein Arnold von, Wu Fredrick C W
Institute of Clinical Chemistry, University Hospital of Zurich, Raemistrasse 100, CH-8091, Zurich, Switzerland.
Growth Horm IGF Res. 2003 Aug;13 Suppl A:S72-84. doi: 10.1016/s1096-6374(03)00059-5.
Hypoandrogenemia in men and hyperandrogenemia in women are associated with increased risk of coronary artery disease but also with visceral obesity, insulin resistance, low high-density lipoprotein (HDL) cholesterol, elevated triglycerides, low-density lipoprotein (LDL) cholesterol and plasminogen activator inhibitor (PAI-1). These gender differences and confounders render the precise role of endogenous androgens in atherosclerosis unclear. Exogenous androgens, on the other hand, induce both apparently beneficial and deleterious effects on cardiovascular risk factors by decreasing serum levels of HDL-C, PAI-1 (apparently deleterious), Lp(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 pro-atherogenic, since it may reflect accelerated reverse cholesterol transport instead.Short-term application of supraphysiological doses of exogenous T can reduce the severity and frequency of angina pectoris and improve the electrocardiographic signs of myocardial ischaemia; long-term effects have not been investigated. Nonetheless, interpretations of the effects of pharmacological doses of androgens on arterial compliance and flow-mediated dilatation in particular must be treated with circumspection also because at physiological concentrations, beneficial, neutral, and detrimental effects on vascular reactivity can be observed.Testosterone exerts 'pro-atherogenic' effects on macrophage function by facilitating the uptake of modified lipoproteins and an 'anti-atherogenic' effect by stimulating efflux of cellular cholesterol to HDL. In the majority of animal experiments, exogenous testosterone exerted neutral or beneficial effects on the development of atherosclerosis. In conclusion, the overall effect of administration of testosterone on cardiovascular-disease risk is difficult to assess because androgens have such an extraordinary array of effects in vivo. When dealing with a complex multifactorial condition such as CAD, it is premature to assume that clinical benefits can be derived from manipulation of the sex steroid milieu - even when these assumptions are based on biologically plausible mechanisms or, indeed, on cross-sectional risk-factor observational data. Neither needs the therapeutic use of testosterone in men be restricted by concerns regarding cardiovascular side effects.
男性雄激素缺乏和女性雄激素过多与冠状动脉疾病风险增加相关，同时也与内脏肥胖、胰岛素抵抗、高密度脂蛋白（HDL）胆固醇水平低、甘油三酯升高、低密度脂蛋白（LDL）胆固醇和纤溶酶原激活物抑制剂（PAI-1）有关。这些性别差异和混杂因素使得内源性雄激素在动脉粥样硬化中的精确作用尚不清楚。另一方面，外源性雄激素对心血管危险因素既有明显有益的影响，也有有害的影响，它可降低男性和女性血清中HDL-C、PAI-1（明显有害）、Lp(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，因为这可能反映了胆固醇逆向转运加速。短期应用超生理剂量的外源性睾酮可减轻心绞痛的严重程度和发作频率，并改善心肌缺血的心电图表现；长期影响尚未进行研究。尽管如此，对雄激素药理剂量对动脉顺应性和血流介导的血管舒张的影响的解释也必须谨慎，因为在生理浓度下，可观察到对血管反应性的有益、中性和有害影响。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。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。总之，由于雄激素在体内具有如此广泛的作用，因此很难评估睾酮给药对心血管疾病风险的总体影响。当处理像冠心病这样复杂的多因素疾病时，即使这些假设基于生物学上合理的机制或横断面危险因素观察数据，认为通过操纵性类固醇环境可获得临床益处还为时过早。男性使用睾酮进行治疗也无需因担心心血管副作用而受到限制。
