雄激素与男性冠心病关系研究近况

冠心病发病的性别差异是近年来研究的热点之一。大量的流行病学及基础研究证实女性绝经期冠心病的发病率明显升高 ,雌激素替代治疗可减少女性冠心病的发病 ,具有抗女性动脉粥样硬化 (AS)的作用。而男性较女性冠心病发病率高的事实曾使人们认为雄激素促使男性冠心病的发生。但是事实并非如此 ,多数临床研究证实雄激素与冠心病的发病呈负相关 ,雄激素具有抗男性 AS的作用。本文就雄激素与男性冠心病的关系作一综述。1　雄激素的组成、代谢及生理功能雄激素是含有 19个碳原子的类固醇 ,具有产生和维持男性生殖器官、生殖功能和第二性征的作用…     

雄激素及雄激素受体与冠心病危险因素的关系

1冠心病危险因素概述 流行病学调查证实,冠心病发病率存在明显的性别差异,男性发病率明显高于绝经期前的同年龄段女性,即使考虑其他发病危险因素,性别仍是一个独立的冠心病危险因子.回顾性研究显示,雄激素水平与男性冠状动脉狭窄严重程度和心肌梗死发生率呈负相关,低雄激素血症可能是老年男性冠心病的独立危险因素之一[1].另外,高血压、糖尿病,肥胖也是冠心病的主要危险因素.一般认为,雄激素的生物活性由雄激素受体（androgen receptor,AR）介导,现就雄激素、AR与高血压、糖尿病、肥胖的关系及其作用机制的研究综述如下.     

雄激素受体与男性心血管疾病

心血管疾病已成为威胁人类健康的重大疾病之一。在其众多的危险因素中,男性性别已成为冠心病的独立危险因素,提示雄激素可能与心血管疾病有一定关系。雄激素对男性性分化、发育和功能的维持有着十分重要的作用。但雄激素的这些作用主要是通过雄激素受体(AR)介导的。我们将介绍A     

雄激素对男性冠心病患者的急性抗缺血作用

由于男性较之同年女性有更高的冠心病发病率,有人推测雄激素是冠脉疾病的病因之一。然而,近期的一些研究显示雄激素能改善男性冠脉的内皮依赖性的舒张功能。因此,该研究旨在评价静脉注射雄激素对男性由运动引发的心肌缺血的作用。     

血清雄激素水平与男性动脉粥样硬化的关系

目的研究男性冠心病患者血清雄激素水平及颈动脉内膜—中膜厚度的变化,以及血清雄激素对血清脂蛋白、血糖、胰岛素抵抗的影响,探讨血清雄激素水平与男性动脉粥样硬化的关系。方法选择经冠状动脉造影证实的男性冠心病病人91例(冠心病组),根据血管病变情况分为单支病变组(n=30)、两支病变组(n=33)和三支病变组(n=28),同时选择冠状动脉造影正常男性43例作为对照组。入选病例均测定血清总睾酮、游离睾酮、去氢表雄酮,血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、脂蛋白a和空腹血糖、空腹胰岛素,以稳态模型评估胰岛素抵抗指数,超声测量颈动脉内膜—中膜厚度。结果冠心病组与对照组比较,血清总胆固醇、低密度脂蛋白、脂蛋白a、空腹胰岛素、空腹血糖、稳态模型评估胰岛素抵抗指数及颈动脉内膜—中膜厚度显著增高(P<0.05),血清高密度脂蛋白胆固醇、游离睾酮显著降低(P<0.001);游离睾酮冠心病各亚组与对照组比差异有显著性(P<0.001);颈动脉内膜—中膜厚度冠心病各亚组均高于对照组(P<0.001),单支病变组低于两支及三支病变组(P<0.01);空腹胰岛素及稳态模型评估胰岛素抵抗指数:冠心病各亚组均显著高于对照组(P<0.01),且三支病变组显著高于单支病变组。Pearson相关分析表明,内膜—中膜厚度与游离睾酮、高密度脂蛋白胆固醇呈显著负相关(r值均小于-0.5,P<0.001),与空腹胰岛素、稳态模型评估胰岛素抵抗指数、低密度脂蛋白胆固醇、脂蛋白a呈显著正相关(r值均大于0.5,P<0.001)。结论男性冠心病患者血清游离睾酮水平下降,游离睾酮通过影响血脂、血糖、胰岛素抵抗等因素参与男性动脉粥样硬化的形成。     

老年男性雄激素及其单核细胞雄激素受体与高血压、冠心病的关系

据流行病学的研究发现,性激素与高血压、冠心病可能存在一定的联系.本研究旨在进一步从细胞分子水平探讨雄激素及其受体与男性高血压、冠心病的关系.     

性激素与动脉粥样硬化、冠心病关系的性别特异性

雌激素的抗动脉粥样硬化 (ＡＳ)、防治女性冠心病作用 ,已为大多数临床及基础研究所证实。虽然临床及基础研究的结果多有冲突 ,但多数研究仍支持生理水平雄激素对男性心血管系统有保护作用 ,冠心病患者较冠脉正常者血清雄激素水平低〔1,2〕。另外一个令人感兴趣的问题是 ,雌激素对男性心血管系统作用如何或雄激素对女性心血管系统是否有害 ,我们对此作一综述。　　一、性激素与冠心病关系的性别特异性　　 1976年Ｐｈｉｌｌｉｐｓ〔3〕在 15例 3 2～ 42岁男性心肌梗死患者中偶然发现多数有女性化的表现 ,心肌梗死患者血清雌二醇 (Ｅ2 )水平…     

雄激素与老年男性冠心病的关系

雄激素具有抗动脉粥样硬化的作用,补充生理剂量雄激素可改善老年男性的心肌缺血。雄激素对冠状动脉粥样硬化性心脏病的作用机制包括很多方面,雄激素可影响脂质代谢、血管张力、凝血纤维溶解系统、内皮细胞功能、血管壁平滑肌、巨噬细胞和雄激素受体及血栓烷A2受体。     

雄激素与男性冠心病

男性人群心血管疾病发病率较绝经前同年龄阶段女性明显为高,即使考虑其它发病危险因素后,男性性别仍是一个独立的心血管疾病发病的危险因子。研究证明,雌激素可以减轻动脉粥样硬化的发生,女性绝经后应用雌激素替代治疗可降低女性冠心病的发病率和改善临床症状;但是,雄激素与冠心病发病关系方面的研究尚无定论,雄激素对动脉粥样硬化形成过程的影响还不清楚,近几年来,国内外对此进行了研究,但还存在着许多问题和相互矛盾之处,本文就这方面的研究进展综述如下。1　雄激素对血浆脂质代谢的影响1.1　内源性雄激素与脂质代谢:Kirland等[1]研究发…     

前言——雄激素与心血管相关危险因素的关系

<正>随着年龄增加,老年男性体内雄激素的水平也逐步下降,身体内的各器官功能逐渐衰退。目前的研究发现,在机体的老化过程及老年性疾病的发生发展中,雄激素的作用不可忽视。雄激素在男性的生长和发育中起了重要的作用,而近些年的研究发现,雄激素对于机体血管内皮细胞功能、血压的调节以及心、脑、肾等人体重要的靶器官也产生一定的影响。因此,探讨雄激素     

Sex,plasma lipoproteins,and atherosclerosis: Prevailing assumptions and outstanding questions

We review the hypothesis that the incidence of coronary heart disease (CHD) is higher in men than in women due to differences in plasma lipoprotein risk factors between the sexes. Men and women appear to be equally susceptible to the effects of lipoprotein risk factors for CHD, and the difference between the sexes in lipoprotein risk factors for CHD appears to be consistent with their being, at least in part, responsible for the sex difference in CHD. This is apparent both when men and women of equal age are compared, and when age-related variations in the sex differences in plasma lipoproteins and CHD are considered. Differences between the sexes in lipoprotein concentrations are still present when sex differences in adiposity, cigarette smoking, physical activity, and diet are taken into account. Evidence relating these sex differences in CHD and lipoproteins to the effects of sex hormones is critically examined. It is commonly accepted that androgens induce changes in lipoprotein concentrations that would predispose towards CHD, whereas estrogens are held to have opposite effects. However, much of the evidence for this comes from studies of changes associated with administration of synthetic gonadal steroids or with changes in gonadal function. Studies of differences in lipoprotein metabolism in normal men and women are extremely limited. In males high-density lipoprotein (HDL) cholesterol levels fall at puberty, correlating with the rise in plasma testosterone concentrations. In females, HDL levels do not change at puberty, despite the rise in estrogen concentrations. Evidence for lipoprotein changes during the menopause, when estrogen levels decline, is equivocal. Similarly, the evidence for an increase in CHD incidence at the menopause is inconclusive. National mortality data indicate that the decreasing sex difference in CHD after 50 years of age is due to a declining rate of increase in men rather than to an acceleration in CHD incidence in women. In men the age-related increase in low-density lipoprotein (LDL) concentrations diminishes beyond 50 years of age, whereas in women the rate of increase remains unchanged. Studies of the effects of gonadectomy are of doubtful relevance in assessing the roles of sex hormones in CHD, and have not been performed with sufficient rigor to provide definitive conclusions. The effects of exogenously administered androgens and estrogens on lipoprotein concentrations have dominated the evaluation of the hypothesis that differences in sex hormones underlie the sex difference in lipoprotein concentrations and hence CHD incidence. However, these studies have been confounded by the variety and nature of gonadal steroids employed, with native (nonsynthetic) hormones being poorly represented. The lack of thorough prospective studies of risk factors for CHD in women, comparative studies of lipoprotein metabolism in healthy men and women, and prospective studies relating endogenous sex hormone levels, plasma lipoprotein concentrations, and development of CHD all remain serious omissions in our understanding of the pathogenesis of the major cause of death in Western society.     

Hormonal effects on blood vessels

The incidence of cardiovascular disease (CVD) is lower in younger women than in men of the same age, but it increases after menopause, implicating the atheroprotective action of endogenous estrogen. Although observational studies have suggested the efficacy of estrogen therapy in postmenopausal women, placebo-controlled, randomized trials, such as the Women's Health Initiative, have not confirmed effects of estrogen therapy on CVD. Conversely, basic, experimental research has progressed and provided mechanistic insight into estrogen's action on blood vessels. By contrast, the vascular effects of androgens remain poorly understood and have been controversial for a long time. In recent years, an increasing body of evidence has suggested that androgens may exert protective effects against the development of atherosclerosis, at least in elderly men. Epidemiological studies have shown that the incidence of and mortality due to CVD were increased in elderly men with low testosterone levels, although the efficacy of androgen therapy remains unknown. Furthermore, recent experimental studies have demonstrated the direct action of androgens on the vasculature. In this review, we illustrate the effects of sex steroids on the cardiovascular system, focusing on the action of testosterone on the blood vessels.     

Risk prediction of coronary heart disease based on retinal vascular caliber (from the Atherosclerosis Risk In Communities [ARIC] Study)

Recent studies showed that such retinal vascular signs as quantitative retinal vascular caliber were associated with increased risk of incident coronary heart disease (CHD), but whether these retinal vascular signs add to the prediction of CHD over and above traditional CHD risk factors was not addressed. Whether these signs add to the prediction of CHD over and above the Framingham risk score in people (n = 9,155) without diabetes selected from the ARIC Study was investigated. Incident CHD was ascertained using standardized methods, and retinal vascular caliber and other retinal signs were measured from retinal photographs. After a mean of 8.8 years of follow-up, there were 700 incident CHD events. Women with wider retinal venular caliber (hazard ratio 1.27/1-SD increase, 95% confidence interval 1.08 to 1.50) and narrower retinal arteriolar caliber (hazard ratio 1.31/1-SD decrease, 95% confidence interval 1.10 to 1.56) had a higher risk of incident CHD after adjusting for Framingham risk score variables. Area under the receiver operator characteristic curve increased from 0.695 to 0.706 (1.7% increase) with the addition of retinal vascular caliber to the Framingham risk model. Risk prediction models with and without retinal vascular caliber both fitted the data and were well calibrated for women. In men, retinal vascular caliber was not associated with CHD risk after adjustment. Other retinal vascular signs were not associated with 10-year incident CHD in men or women. In conclusion, although retinal vascular caliber independently predicted CHD risk in women, the incremental predictive ability over that of the Framingham model was modest and unlikely to translate meaningfully into clinical practice.     

Coronary heart disease prevention in women: focus on lipids

Coronary heart disease (CHD) remains an urgent and leading threat to women's health and well-being. Clinical trials have demonstrated a clear cut benefit of low density lipoprotein cholesterol (LDL-C) lowering in both women as well as men with coronary disease. While the case for primary prevention of CHD with LDL-C lowering is less secure in both men and women, there is little doubt that patients at high risk of CHD, even without a prior history of vascular events, will in the long run benefit from LDL-C lowering. Thus, all available evidence indicates that lipid interventions should be pursued aggressively in both women and men at risk of CHD.     

Testosterone and cardiovascular disease: An old idea with modern clinical implications

The role of sex steroid hormones in modulating vascular function in men is of great importance, given that androgen deficiency is strongly associated with common medical conditions including metabolic syndrome, obesity, diabetes, hypertension and atherosclerosis. Testosterone deficiency afflicts approximately 30% of men ages 40–79 years. Testosterone replacement in deficient men with such co-morbidities ameliorates or partially reverses their progression. Studies in animal and humans suggest that androgen deficiency is associated with increased triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Emerging evidence indicates that androgens may provide a protective effect against the development and/or progression of atherosclerosis in men.     

Cardiovascular Effects of Androgens

In the process of atherosclerosis sex steroids play a complex role in the vascular vessel wall system. Although a number of experimental studies have clearly documented an atheroprotective effect of estrogens, in recent clinical studies, estrogen replacement therapy has failed to reduce cardiovascular mortality. The effects of androgens on the cardiovascular system and cardiovascular diseases are even more controversial. Whereas in the past, androgens were mainly believed to exert adverse effects on the cardiovascular system, recent studies in men have documented a number of beneficial actions of testosterone in the arterial vascular system. Androgens affect lipid metabolism (e.g., LDL and HDL cholesterol, Lp(a)) and hemostasis (e.g., platelet aggregation and fibrinolytic activity). In addition, several other physiological and pathophysiological processes in the arterial vessel wall are influenced by androgens. Acute hemodynamic effects of testosterone on coronary vasomotion and stress‐test‐induced ischemia were reported. Additionally, recent animal and in vitro studies have further documented an inhibitory effect of androgens on neointimal plaque formation. This review discusses different and, in part, contradictory effects of androgens on the cardiovascular system including potential signal transduction pathways in androgen target cells.     

关于女性冠心病相关危险因素的研究进展

传统意义上认为女性因为有雌激素对血管壁的保护作用,故年轻时冠心病的发病率和病死率低于男性,但近几年来国内外研究表明女性冠心病发病率有显著升高的趋势,且趋于年轻化。本文主要从冠心病的传统危险因素、新发的危险因素及其标志物和女性的社会心理因素方面进行探讨,从而提高对女性冠心病的认识,更好地进行预防。     

Gender disparity in outcomes of care and management for diabetes and the metabolic syndrome

Although diabetes lies among the major risk factors for cardiovascular disease (CVD) in both men and women, current evidence suggests that it has a much stronger effect on the risk of coronary heart disease (CHD) in women than in men. Moreover, diabetic women have not experienced the decline in CHD mortality observed in diabetic men and individuals without diabetes over the past three decades. Apart from a more pronounced direct effect of diabetes on the vascular wall, this greater impact of diabetes on CHD risk in women could be associated with a heavier burden of other traditional cardiovascular risk factors within the context of the metabolic syndrome, a stronger effect of the metabolic syndrome on CVD, and a less aggressive management of the various risk factors in diabetic women compared with men. This article discusses the recent evidence on the gender differences in the outcomes of CVD and the management of risk factors associated with diabetes and the metabolic syndrome, highlighting the need for better treatment strategies of diabetes and the other components of the metabolic syndrome in diabetic women.     

Metabolic syndrome and vascular risk: a 9-year follow-up among the aged in Finland

The aim was to analyze the relationship between metabolic syndrome (MetS) and vascular risk among the aged. A prospective population-based study, with a 9-year follow-up. All subjects of the municipality of Lieto in Finland aged ≥64 in 1998–99 participated (n = 1183). Hazard ratios (HRs) for fatal or non-fatal coronary (CHD), cerebrovascular (CV), or all vascular events predicted by MetS (defined by International Diabetes Federation) were estimated. During the 9-year follow-up, a total of 348 vascular events occurred, including 208 CHD and 150 CV events. After multivariable adjustment, CHD events (1.70, 1.07–2.71, P = .026) and vascular events (1.57, 1.07–2.30, P = .021) were more common in men with MetS compared to men without it. Evaluating MetS components individually, low HDL-cholesterol among women predicted a higher occurrence of CV (2.44, 1.46–4.09, P < .001) and all vascular (1.78, 1.26–2.53, P = .001) events. Elevated blood pressure among men was related to fewer CHD events (0.46, 0.25–0.83, P = .010). Our findings suggest that MetS does predict vascular events in late life among men. In older women, only low HDL-cholesterol was associated with vascular risk. Slightly or moderately elevated blood pressure values do not predict vascular events in this age group.     

Androgens and Androgen Receptors as Determinants of Vascular Sex Differences Across the Lifespan

Androgens, including testosterone and its more potent metabolite dihydrotestosterone, exert multiple actions in the body. Physiologically, they play a critical role in male sex development. In addition, they influence vascular function, including arterial vasodilation and mediation of myogenic tone. Androgens are produced from 9 weeks' gestation in the human fetal testis, as well as in small amounts by the adrenal glands. Serum concentrations vary according to age and sex. The vasculature is a target for direct actions of androgens, which bind to various sex hormone receptors expressed in endothelial and vascular smooth muscle cells. Androgens exert both vasoprotective and vasoinjurious effects, depending on multiple factors including sex-specific effects of androgens, heterogeneity of the vascular endothelium, differential expression of androgen and sex hormone receptors in endothelial and vascular smooth muscle cells, and the chronicity of androgen administration. Long-term administration of androgens induces vasoconstriction and influences endothelial permeability, whereas acute administration may have opposite effects. At the cellular level, androgens stimulate endothelial cell production of nitric oxide and inhibit proinflammatory signalling pathways, inducing vasorelaxation and vasoprotection. However, androgens also activate endothelial production of vasoconstrictors and stimulate recruitment of endothelial progenitor cells. In humans, both androgen deficiency and androgen excess are associated with increased cardiovascular morbidity and mortality. This review discusses how androgens modulate vascular sex differences across the lifespan by considering the actions and production of androgens in both sexes and describes how cardiovascular risk is altered as levels of androgens change with aging.