雄激素与糖脂代谢的关系

雄激素是男性体内较为重要的一种激素,除维持男性特征外,还参与机体多种生理代谢过程,具有重要的物质代谢调节作用.男性雄激素水平低下,可增加代谢综合征、2型糖尿病、动脉粥样硬化等代谢性疾病的发病率.此外,女性雄激素水平升高与胰岛素抵抗及脂代谢紊乱也有关,雄激素对血糖、血脂、脂肪细胞因子和机体组分均可产生重要影响.     

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     

雄激素与男性冠心病的关系

雄激素与男性冠心病的关系存有较多争议,但多数研究发现雄激素有抗动脉粥样硬化的作用,男性雄激素水平的降低与冠心病的发生密切相关。雄激素通过影响人体的脂质代谢、凝血纤溶系统、血管张力及血管内皮功能对抗男性冠心病的形成和发展。     

睾酮对动脉粥样硬化的影响及机理

睾酮具有抗动脉粥样硬化的作用,补充睾酮治疗可改善男性的心肌缺血.睾酮可影响脂质代谢、凝血纤溶系统;在细胞水平影响内皮细胞、血管壁平滑肌及巨噬细胞功能;在受体水平影响雄激素受体及血栓素A2受体.     

雄激素与男性动脉粥样硬化的关系

男性雄激素与动脉粥样硬化形成有关,它可以通过影响血脂代谢、内皮细胞、巨噬细胞、平滑肌细胞、凝血功能等因素起到抗动脉粥样硬艇,进一步深入研究雄激素抗动脉粥样硬化的机制,将为预防和治疗男性动脉粥样硬化提供重要的依据。     

雄激素对盐敏感高血压及其靶器官影响的研究进展

盐与高血压及其靶器官损伤有着密切的联系,已得到了公认。雄激素在机体的生长发育、维持男性生殖功能等方面起着重要的生理功能。最新的研究发现,雄激素对盐敏感高血压及其靶器官损伤有着重要的影响,可进一步提高盐敏感性高血压的血压水平,促进盐敏感性高血压实验动物心肌肥厚、增加蛋白尿等靶器官损伤。现对近几年国内外关于雄激素在盐敏感高血压及其靶器官损伤中的作用作一综述,并对相关机制进行探讨。     

雄激素对内皮相关心血管系统的影响

雄激素对心血管系统具有重要影响,在血管内皮受损过程中,睾酮可以促进内皮细胞增殖、迁移、修复,改善内皮功能.生理水平的雄激素可以抑制动脉粥样硬化的发生发展;可以改善脂质的代谢.对血压影响的研究存在不同意见,与以往不同,目前研究表明雄激素具有升高血压作用.另外,睾酮水平与血糖、血脂、肥胖负相关;可以抑制炎症因子的表达.     

老年男性代谢综合征患者性激素和性激素受体的变化

目的 探讨老年男性代谢综合征患者性激素和性激素受体与老年男性代谢综合征各组分的相互关系. 方法老年男性587例,其中代谢综合征患者187例(代谢综合征组),健康人400例(健康组).测定总睾酮(TT)、游离睾酮(FT)、脱氢表雄酮硫酸酯(DHEAS)、性激素结合球蛋白(SHBG)、雌二醇(E2)、黄体生成素(LH)、卵泡刺 激素(FSH)水平,同时采用流式细胞术检测外周血雄激素受体(AR)水平.结果 代谢综合征组患者DHAES、TT、SHBG、FT、AR荧光强度均低于健康组,而FSH、E2高于健康组.年龄与舒张压、FT呈负相关,与收缩压、E2 呈正相关.AR荧光强度与收缩压、LH呈负相关.DHEAS、SHBG进入logistic回归方程,与代谢综合征的发病呈负相关趋势.结论 老年男性代谢综合征患者存在低水平的DHEAS、TT、SHBG、FT、AR,同时存在高水平的FSH、E2;低水平的DHEAS、SHBG可能是老年男性代谢综合征潜在的危险因素.     

男性骨质疏松症

男性也有更年期,因男性雄激素水平的减退是渐进性的,故更年期不易察觉。更年期影响男性健康,包括发生骨质疏松症。男性原发性骨质疏松症的发病年龄多在70岁以后。同女性一样,骨质疏松性骨折是最严重的并发症,髋部骨折死亡率高于女性。雄激素水平下降是男性骨质疏松症的重要发病因素,高龄引起的其他内分泌变化对发病也有影响。不良的生活习惯多发生于男性,其在骨丢失中的重要性大于女性。一生中每个阶段的骨量男性都高于同阶段女性。男性骨丢失缓慢发生,无快速骨丢失期,其诊断参考女性标准,并应测血中睾酮水平。钙、维生素D、二膦酸盐等可用于治疗。确有雄激素水平低下者,雄激素替代疗法有应用价值。     

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。     

中老年男性睾酮水平与代谢综合征的相关性

目的探讨50～70岁中老年男性睾酮水平与代谢综合征（MS）的相关性。方法收集我院2005年9月至2006年9月门诊及住院50—70岁男性200例。按2005年国际糖尿病联盟关于MS的临床判断标准分成2组，MS组80例和无MS组（NMS组）120例。比较2组间睾酮水平的差异，分析2组睾酮与腰围、BMI、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL—C）的相关性。结果2组间年龄无统计学差异（P〉0．05）。MS各成分中，除腰围及BMI2组间有明显差异，MS组明显高于NMS组，糖尿病比例、高血压比例、TG、HDL—C2组间均无明显差异。2组间睾酮水平比较，MS组睾酮水平（4.11±1．22）μg／L明显低于NMS组（5．964±1．73）μg／L（P〈0．01）。相关性分析显示，在MS组及NMS组睾酮水平均与年龄、腰围呈负相关，在NMS组睾酮水平尚与HDL—C呈正相关。结论50～70岁中老年男性更低的睾酮水平可能进一步增加MS的患病风险。     

Metabolic Syndrome,Androgens, and Hypertension

Obesity is one of the constellation of factors that make up the definition of the metabolic syndrome. Metabolic syndrome is also associated with insulin resistance, dyslipidemia, hypertriglyceridemia, and type 2 diabetes mellitus. The presence of obesity and metabolic syndrome in men and women is also associated with increased risk of cardiovascular disease and hypertension. In men, obesity and metabolic syndrome are associated with reductions in testosterone levels. In women, obesity and metabolic syndrome are associated with increases in androgen levels. In men, reductions in androgen levels are associated with inflammation, and androgen supplements reduce inflammation. In women, increases in androgens are associated with increases in inflammatory cytokines, and reducing androgens reduces inflammation. This review discusses the possibility that the effects of androgens on metabolic syndrome and its sequelae may differ between males and females.     

Androgens and glucuronidated androgen metabolites are associated with metabolic risk factors in men

CONTEXT: Androgens are associated with metabolic risk factors in men. However, the independent impact of androgens and androgen metabolites on metabolic risk factors in men is unclear. OBJECTIVE: Our objective was to determine the predictive value of serum levels of androgens and glucuronidated androgen metabolites for metabolic risk factors. DESIGN AND STUDY SUBJECTS: We conducted a population-based study of two Swedish cohorts (1,068 young adult and 1,001 elderly men). MAIN OUTCOME MEASURES: We measured correlation of serum dihydrotestosterone (DHT), testosterone (T), and glucuronidated androgen metabolites with fat mass, fat distribution, serum lipids, and insulin resistance. RESULTS: Both DHT and T were negatively associated with different measures of fat mass in both cohorts (P < 0.001). Further statistical analysis indicated that DHT, but not T, was independently negatively associated with different measures of fat mass and insulin resistance (P < 0.001). The glucuronidated androgen metabolite androstane-3alpha,17beta-diol-17glucuronide (17G) was independently positively associated with fat mass (P < 0.001). Most importantly, the 17G to DHT ratio was strongly correlated, not only with fat mass but also with central fat distribution, intrahepatic fat, disturbed lipid profile, insulin resistance, and diabetes, explaining a substantial part of the total variance in total body fat (12% in young adult men, 15% in elderly men), the homeostasis model assessment index (10%), and high-density lipoprotein cholesterol (7%). CONCLUSION: Our findings demonstrate that 17-glucuronidation of the DHT metabolite androstane-3alpha,17beta-diol is strongly associated with several metabolic risk factors in men. Future longitudinal studies are required to determine the possible impact of the 17G to DHT ratio as a metabolic risk factor in men.     

Unanswered Questions Regarding the Effect of Androgen Deprivation Therapy for Prostate Cancer on Cardiovascular Disease Risk in Black Men

Prostate cancer is the most common visceral malignancy affecting men in the United States. Patient tailored therapy is based on risk group categories. In recent years, androgen deprivation therapy has played a greater role in the treatment of prostate cancer. However, androgen suppression can lead to changes in the metabolic profile that increase the risk of cardiovascular disease in men. Evidence is emerging that hormonal therapy increases the risk of cardiac morbidity and mortality. This finding is of particular concern for black men. Compared with other racial and ethnic groups, black men in the United States have the highest prevalence of both prostate cancer and cardiovascular mortality. Due to increased utilization of hormone therapy in the treatment of prostate cancer, and high prevalence of prostate cancer in blacks, the risk of cardiac disease following androgen deprivation therapy in black men needs to be determined.     

Obesity and testicular function

Obesity in men, particularly when central, is associated with lower total testosterone [TT], free testosterone [FT] and sex hormone-binding globulin [SHBG], and a greater decline in TT and FT with increasing age compared with lean men. Obesity-related conditions such as obstructive sleep apnea, insulin resistance and type 2 diabetes mellitus are independently associated with decreased plasma testosterone. Possible mechanisms include decreased LH pulse amplitude, inhibitory effects of oestrogen at the hypothalamus and pituitary and the effects of leptin and other peptides centrally and on Leydig cells. Obese men have reduced sperm concentration and total sperm count compared to lean men but sperm motility and morphology appear unaffected. The cause and effect relationships between low plasma androgen levels, obesity and the metabolic syndrome, and associated cardiometabolic risk remain unclear. While weight loss normalizes TT and FT in obese men, androgen replacement in the short term does not significantly improve cardiometabolic risk profile despite reducing fat mass.     

Contribution of age and declining androgen levels to features of the metabolic syndrome in men

Plasma dehydroepiandrosterone sulfate (DHEA-S) and testosterone levels both decline with age in healthy men. Features of the metabolic syndrome also show age-related deteriorations. We examined the relative contribution of age and declining androgen levels to features of the metabolic syndrome in men. In a sample of 130 nonsmoking men from the Quebec Family Study, we tested the hypothesis that age-related decreases in DHEA-S and testosterone levels would explain most of the variance in alterations of the metabolic profile associated with aging. As expected, we found that plasma DHEA-S and testosterone levels were negatively associated with age. Significant negative correlations were found between androgen levels and adiposity measures, body fat distribution, and metabolic risk variables. Statistical control for age eliminated correlations with DHEA-S, whereas age-adjusted associations between testosterone and most adiposity and metabolic variables remained significant. The percentage frequency of men characterized by 3 or more features of the metabolic syndrome increased with decreasing testosterone (8.9%-44.2%, chi2 = 15.89, P < .0005 ) and DHEA-S levels (8.9%-41.5%, chi2 = 13.02, P < .005). Logistic regression analyses showed that men in the upper tertile of testosterone levels had a lower risk of being characterized by 3 or more features of the metabolic syndrome (odds ratio = 0.24, P < .04) independent of age, whereas tertiles of DHEA-S levels were not related to the metabolic syndrome independent of age. In conclusion, results suggest that age per se is an important correlate of the associations between DHEA-S and metabolic variables, whereas the association of plasma testosterone levels to features of the metabolic syndrome appears to be independent of age.     

Androgen deprivation by activating the liver X receptor

Prostate cancer is the most commonly diagnosed and the second leading cause of cancer death in men. The androgens-androgen receptor signaling plays an important role in normal prostate development, as well as in prostatic diseases, such as benign hyperplasia and prostate cancer. Accordingly, androgen ablation has been the most effective endocrine therapy for hormone-dependent prostate cancer. Here, we report a novel nuclear receptor-mediated mechanism of androgen deprivation. Genetic or pharmacological activation of the liver X receptor (LXR) in vivo lowered androgenic activity by inducing the hydroxysteroid sulfotransferase 2A1, an enzyme essential for the metabolic deactivation of androgens. Activation of LXR also inhibited the expression of steroid sulfatase in the prostate, which may have helped to prevent the local conversion of sulfonated androgens back to active metabolites. Interestingly, LXR also induced the expression of selected testicular androgen synthesizing enzymes. At the physiological level, activation of LXR in mice inhibited androgen-dependent prostate regeneration in castrated mice. Treatment with LXR agonists inhibited androgen-dependent proliferation of prostate cancer cells in a LXR- and sulfotransferase 2A1-dependent manner. In summary, we have revealed a novel function of LXR in androgen homeostasis, an endocrine role distinct to the previously known sterol sensor function of this receptor. LXR may represent a novel therapeutic target for androgen deprivation, and may aid in the treatment and prevention of hormone-dependent prostate cancer.     

Androgen deprivation therapy in prostate cancer and metabolic risk for atherosclerosis

CONTEXT: Prostate cancer (PCa) is the most common cancer in men. Androgen-deprivation therapy (ADT) is generally employed in the treatment of locally advanced and metastatic PCa. Although its use as an adjuvant therapy has resulted in improved survival in some patients, ADT has negative consequences. Complications like osteoporosis, sexual dysfunction, gynecomastia, and adverse body composition are well known. Recently, metabolic complications like insulin resistance, diabetes, dyslipidemia, and metabolic syndrome have emerged, which may be responsible for the increased cardiovascular mortality in this population. EVIDENCE ACQUISITION: A MEDLINE search was conducted for articles published over the last 20 yr based on the key words androgen deprivation therapy AND insulin resistance, hyperglycemia, diabetes, dyslipidemia, metabolic syndrome, and cardiovascular disease. Relevant studies in non-PCa populations evaluating the association between testosterone and metabolism were also reviewed and briefly mentioned where relevant. EVIDENCE SYNTHESIS: Prospective studies evaluating early (3-6 months) metabolic changes of ADT show development of hyperinsulinemia; however, glucose levels remain normal. Cross-sectional studies of men undergoing long-term (> or =12 months) ADT reveal higher prevalence of diabetes and metabolic syndrome compared with controls. Furthermore, men undergoing ADT also experience higher cardiovascular mortality. CONCLUSION: Long-term prospective studies of ADT are needed to determine the timing of onset of these metabolic complications and to investigate the mechanism behind them. In the meantime, we recommend baseline and serial screening for fasting glucose, lipids, and other cardiovascular risk factors in men receiving ADT. Glucose tolerance tests and cardiac evaluation may be required in selected cases.     

Role of endogenous androgen against insulin resistance and athero- sclerosis in men with type 2 diabetes

Age-related decline in serum testosterone and dehydroepiandrosterone sulfate concentrations occur in men. Low concentrations of these endogenous androgens have been linked with insulin resistance, which is an important upstream driver for metabolic abnormalities such as hyperglycemia, hypertension, or hyperlipidemia, and increased cardiovascular risk. Moreover, men with diabetes have significantly less circulating androgen than nondiabetic men. Here, we summarize how androgen affects insulin resistance and atherosclerosis in men with type 2 diabetes. Low serum concentrations of endogenous androgens are associated with visceral fat accumulation. Androgen deprivation by castration to treat prostate cancer increases insulin resistance, while testosterone administration in type 2 diabetic men with androgen deficiency improves glucose homeostasis and decreases visceral fat, in addition to alleviating symptoms of androgen deficiency including erectile dysfunction. Androgen correlates inversely with severity of atherosclerosis and has beneficial effects upon vascular reactivity, inflammatory cytokine, adhesion molecules, insulin resistance, serum lipids, and hemostatic factors. Because men with type 2 diabetes have relative hypogonadism, testosterone supplementation could decrease both insulin resistance and atherosclerosis.