Center for Research in Reproduction and Contraception, Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
Clin Endocrinol (Oxf). 2012 Feb;76(2):281-8. doi: 10.1111/j.1365-2265.2011.04189.x.
In men with prostate cancer, androgen deprivation reduces insulin sensitivity; however, the relative roles played by testosterone and estradiol are unknown. To investigate the respective effects of these hormones on insulin sensitivity in men, we employed a model of experimental hypogonadism with or without hormone replacement.
Placebo-controlled, randomized trial.
Twenty-two healthy male volunteers, 18-55 years old.
Following screening, subjects received the gonadotrophin-releasing hormone antagonist acyline plus one of the following for 28 days: Group 1, placebo transdermal gel and placebo pills; Group 2, transdermal testosterone gel 10 g/day plus placebo pills; Group 3, transdermal testosterone gel 10 g/day plus the aromatase inhibitor anastrozole 1 mg/day to normalize testosterone while selectively reducing serum estradiol. Fasting insulin, glucose, adipokines and hormones were measured bi-weekly.
With acyline administration, serum testosterone was reduced by >90% in all subjects in Group 1. In these men, mean fasting insulin concentrations were significantly increased compared with baseline (P = 0·02) at 28 days, despite stable body weight and no changes in fasting glucose concentrations. Decreased insulin sensitivity was also apparent in the insulin sensitivity indices homeostasis model of insulin resistance (P = 0·03) and quantitative insulin sensitivity check index (P = 0·04). In contrast, in Groups 2 and 3, testosterone concentrations remained in the physiologic range, despite significant reduction in mean estradiol in Group 3. In these groups, no significant changes in insulin sensitivity were observed.
Acute testosterone withdrawal reduces insulin sensitivity in men independent of changes in body weight, whereas estradiol withdrawal has no effect. Testosterone appears to maintain insulin sensitivity in normal men.
在患有前列腺癌的男性中，雄激素剥夺会降低胰岛素敏感性；然而，睾酮和雌二醇的相对作用尚不清楚。为了研究这些激素对男性胰岛素敏感性的各自影响，我们采用了实验性性腺功能减退症伴或不伴激素替代的模型。
安慰剂对照、随机试验。
22 名健康男性志愿者，年龄 18-55 岁。
筛选后，受试者接受促性腺激素释放激素拮抗剂 acyline 加以下一种治疗 28 天：第 1 组，安慰剂透皮凝胶和安慰剂丸；第 2 组，每天 10 克透皮睾酮凝胶加安慰剂丸；第 3 组，每天 10 克透皮睾酮凝胶加芳香酶抑制剂阿那曲唑 1 毫克/天，以在选择性降低血清雌二醇的同时使睾酮正常化。每两周测量一次空腹胰岛素、血糖、脂联素和激素。
在所有第 1 组受试者中，acyline 给药后血清睾酮降低了>90%。在这些男性中，与基线相比，28 天时空腹胰岛素浓度显著升高（P = 0.02），尽管体重稳定，空腹血糖浓度没有变化。胰岛素敏感性指数稳态模型评估的胰岛素抵抗（P = 0.03）和定量胰岛素敏感性检查指数（P = 0.04）也明显降低。相比之下，在第 2 组和第 3 组中，尽管第 3 组平均雌二醇显著降低，但睾酮浓度仍保持在生理范围内。在这些组中，未观察到胰岛素敏感性的显著变化。
急性睾酮撤退会降低男性的胰岛素敏感性，而与体重变化无关，而雌二醇撤退则没有影响。睾酮似乎维持正常男性的胰岛素敏感性。
