Testosterone and atherosclerosis
Testosterone and atherosclerosis
复制标题
DOI：
10.1016/s1096-6374(03)00059-5
复制
发表时间：
2003-08-01
影响因子：
1.4
通讯作者：
Wu, FCW
中科院分区：
文献类型：
--
作者：
von Eckardstein, A;Wu, FCW
男性的低雄激素血症和女性的高雄激素血症与冠状动脉疾病的风险增加有关，但也与内脏肥胖、胰岛素抵抗、低高密度脂蛋白（HDL）胆固醇、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确切作用不清楚。另一方面，外源性雄激素通过降低男性和女性的血清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），对心血管危险因素产生明显有益和有害的影响。然而，雄激素诱导的循环HDL-C下降不应自动假定为促动脉粥样硬化，因为它可能反映了加速的胆固醇逆向转运，而不是短期应用超生理剂量的外源性T可以降低心绞痛的严重程度和频率，改善心肌缺血的心电图体征;长期影响尚未调查。尽管如此，雄激素的药理剂量对动脉顺应性和血流介导的扩张的影响的解释，特别是必须谨慎对待，也因为在生理浓度，有益的，中性的，通过促进修饰脂蛋白的摄取和抗脂质过氧化作用，在大多数动物实验中，外源性睾酮对动脉粥样硬化的发展产生中性或有益的影响。总之，由于雄激素在体内具有如此非凡的一系列作用，因此很难评估睾酮对心血管疾病风险的总体作用。在处理复杂的多因素疾病（如CAD）时，假设可以从性类固醇环境的操纵中获得临床益处还为时过早-即使这些假设是基于生物学上合理的机制，或者实际上是基于横截面风险因素的观察数据。男性睾酮的治疗用途也不需要受到心血管副作用的限制。(C)2003爱思唯尔科技有限公司版权所有。
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-I). 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-I (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. (C) 2003 Elsevier Science Ltd. All rights reserved.