急性性类固醇撤药会降低患有特发性低促性腺激素性性腺功能减退的健康男性的胰岛素敏感性。

Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism.

作者信息

Yialamas Maria A, Dwyer Andrew A, Hanley Erin, Lee Hang, Pitteloud Nelly, Hayes Frances J

机构信息

Reproductive Endocrine Unit of the Department of Medicine , Massachusetts General Hospital, Bartlett Hall Extension 511, Boston, Massachusetts 02114, USA.

出版信息

J Clin Endocrinol Metab. 2007 Nov;92(11):4254-9. doi: 10.1210/jc.2007-0454. Epub 2007 Aug 28.

DOI:10.1210/jc.2007-0454

PMID:17726076

Abstract

CONTEXT

Evidence suggests that testosterone (T) influences insulin sensitivity in men. The mechanism of this effect is unclear but is thought to involve changes in body composition.

OBJECTIVE

The aim of this study was to determine whether acute sex steroid withdrawal decreases insulin sensitivity in young, healthy men with idiopathic hypogonadotropic hypogonadism (IHH).

DESIGN

This was a 2-wk prospective study.

SETTING

The study was conducted at a General Clinical Research Center.

PATIENTS

Twelve men with IHH (age 40.8 +/- 2.8 yr) were studied: 1) on hormone replacement with normal T levels and 2) 2 wk after discontinuing therapy.

MAIN OUTCOME MEASURES

Each evaluation comprised a 75-g oral glucose tolerance test with assessment of insulin sensitivity (fasting insulin levels, homeostatic model assessment for insulin resistance, and Matsuda insulin sensitivity index) and insulin secretion (corrected insulin response). Serum cortisol, leptin, adiponectin, free fatty acids, IL-6, C-reactive protein, and TNF-alpha levels were also measured.

RESULTS

Body mass index was unchanged (27.1 +/- 1.1 to 27.2 +/- 1.1 kg/m(2)). Serum T levels decreased from 529 +/- 65 to 28 +/- 8 ng/dl (P < 0.00005). Fasting insulin levels increased from 4.9 +/- 0.7 to 6.2 +/- 0.6 microU/ml (P = 0.005), homeostatic model assessment of insulin resistance increased from 1.07 +/- 0.2 to 1.4 +/- 1.01 (P < 0.005), and insulin sensitivity index decreased from 11.0 +/- 2.3 to 7.5 +/- 0.7 (P < 0.05). There was a trend for fasting glucose levels to increase, 86.7 +/- 1.3 to 90.8 +/- 1.7 mg/dl (P = 0.09). IL-6 levels increased from 1.2 +/- 0.2 to 2.4 +/- 0.5 pg/ml (P < 0.01), whereas TNF-alpha levels decreased from 1.0 +/- 0.1 to 0.6 +/- 0.1 pg/ml (P < 0.05). No other significant changes were observed.

CONCLUSIONS

Acute sex steroid withdrawal reduces insulin sensitivity in young healthy IHH men. 2) The acuity of the hypogonadism and absence of changes in body mass index or leptin levels suggest that sex steroids modulate insulin sensitivity in the absence of apparent or detectable changes in body composition.

摘要

背景

有证据表明睾酮（T）会影响男性的胰岛素敏感性。这种作用的机制尚不清楚，但认为与身体成分的变化有关。

目的

本研究旨在确定急性性类固醇戒断是否会降低患有特发性低促性腺激素性性腺功能减退（IHH）的年轻健康男性的胰岛素敏感性。

设计

这是一项为期2周的前瞻性研究。

地点

该研究在一个综合临床研究中心进行。

患者

对12名患有IHH的男性（年龄40.8±2.8岁）进行了研究：1）处于睾酮水平正常的激素替代治疗状态；2）停止治疗2周后。

主要观察指标

每次评估均包括一项75克口服葡萄糖耐量试验，评估胰岛素敏感性（空腹胰岛素水平、胰岛素抵抗的稳态模型评估以及松田胰岛素敏感性指数）和胰岛素分泌（校正后的胰岛素反应）。还测量了血清皮质醇、瘦素、脂联素、游离脂肪酸、白细胞介素-6、C反应蛋白和肿瘤坏死因子-α水平。

结果

体重指数未发生变化（从27.1±1.1降至27.2±1.1kg/m²）。血清睾酮水平从529±65降至28±8ng/dl（P<0.00005）。空腹胰岛素水平从4.9±0.7升至6.2±0.6μU/ml（P=0.005），胰岛素抵抗的稳态模型评估从1.07±0.2升至1.4±1.01（P<0.005），胰岛素敏感性指数从11.0±2.3降至7.5±0.7（P<0.05）。空腹血糖水平有升高趋势，从86.7±1.3升至90.8±1.7mg/dl（P=0.09）。白细胞介素-6水平从1.2±0.2升至2.4±0.5pg/ml（P<0.01），而肿瘤坏死因子-α水平从1.0±0.1降至0.6±0.1pg/ml（P<0.05）。未观察到其他显著变化。