Jones Richard D, Nettleship Joanne E, Kapoor Dheeraj, Jones Hugh T, Channer Kevin S
Academic Unit of Endocrinology, Division of Genomic Medicine, Hormone & Vascular Biology Group, The University of Sheffield, Sheffield, UK.
Am J Cardiovasc Drugs. 2005;5(3):141-54. doi: 10.2165/00129784-200505030-00001.
Two of the strongest independent risk factors for coronary heart disease (CHD) are increasing age and male sex. Despite a wide variance in CHD mortality between countries, men are consistently twice as likely to die from CHD than their female counterparts. This sex difference has been attributed to a protective effect of female sex hormones, and a deleterious effect of male sex hormones, upon the cardiovascular system. However, little evidence suggests that testosterone exerts cardiovascular harm. In fact, serum levels of testosterone decline with age, and low testosterone is positively associated with other cardiovascular risk factors. Furthermore, testosterone exhibits a number of potential cardioprotective actions. For example, testosterone treatment is reported to reduce serum levels of the pro-inflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha, and to increase levels of the anti-inflammatory cytokine IL-10; to reduce vascular cell adhesion molecule (VCAM)-1 expression in aortic endothelial cells; to promote vascular smooth muscle and endothelial cell proliferation; to induce vasodilatation and to improve vascular reactivity, to reduce serum levels of the pro-thrombotic factors plasminogen activator inhibitor (PAI)-1 and fibrinogen; to reduce low-density lipoprotein-cholesterol (LDL-C); to improve insulin sensitivity; and to reduce body mass index and visceral fat mass. These actions of testosterone may confer cardiovascular benefit since testosterone therapy reduces atheroma formation in cholesterol-fed animal models, and reduces myocardial ischemia in men with CHD. Consequently, an alternative hypothesis is that an age-related decline in testosterone contributes to the atherosclerotic process. This is supported by recent findings, which suggest that as many as one in four men with CHD have serum levels of testosterone within the clinically hypogonadal range. Consequently, restoration of serum levels of testosterone via testosterone replacement therapy could offer cardiovascular, as well as other, clinical advantages to these individuals.
冠心病（CHD）最强的两个独立危险因素是年龄增长和男性性别。尽管各国冠心病死亡率差异很大，但男性死于冠心病的可能性始终是女性的两倍。这种性别差异归因于女性性激素对心血管系统的保护作用以及男性性激素的有害作用。然而，几乎没有证据表明睾酮会对心血管造成损害。事实上，睾酮的血清水平会随着年龄的增长而下降，低睾酮水平与其他心血管危险因素呈正相关。此外，睾酮还具有许多潜在的心脏保护作用。例如，据报道，睾酮治疗可降低促炎细胞因子白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α的血清水平，并提高抗炎细胞因子IL-10的水平；降低主动脉内皮细胞中血管细胞粘附分子（VCAM）-1的表达；促进血管平滑肌和内皮细胞增殖；诱导血管舒张并改善血管反应性；降低促血栓形成因子纤溶酶原激活物抑制剂（PAI）-1和纤维蛋白原的血清水平；降低低密度脂蛋白胆固醇（LDL-C）；提高胰岛素敏感性；降低体重指数和内脏脂肪量。睾酮的这些作用可能带来心血管益处，因为睾酮治疗可减少胆固醇喂养动物模型中的动脉粥样硬化形成，并减少冠心病男性的心肌缺血。因此，另一种假说是，睾酮随年龄的下降会促进动脉粥样硬化进程。这得到了最近研究结果的支持，这些结果表明，多达四分之一的冠心病男性血清睾酮水平处于临床性腺功能减退范围内。因此，通过睾酮替代疗法恢复血清睾酮水平可能会为这些个体带来心血管以及其他方面的临床益处。
