Acute testosterone deprivation reduces insulin sensitivity in men

Abstract

Objective: 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.

Design: Placebo-controlled, randomized trial.

Participants: Twenty-two healthy male volunteers, 18-55 years old.

Methods: 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.

Results: 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.

Conclusions: 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.

© 2011 Blackwell Publishing Ltd.

Figures

Figure 1

Serum luteinizing hormone (A), testosterone (B) and estradiol (C) over time in healthy young men administered the GnRH antagonist acyline and placebo testosterone (solid line, n=8), acyline and testosterone (broken line, n=6) or acyline, testosterone and the aromatase inhibitor anastrozole (dotted line, n=8). Normal ranges are designated by the thin dotted lines. Values are expressed as means ± standard deviation (SD). *p

Figure 1

Serum luteinizing hormone (A), testosterone (B) and estradiol (C) over time in healthy young men administered the GnRH antagonist acyline and placebo testosterone (solid line, n=8), acyline and testosterone (broken line, n=6) or acyline, testosterone and the aromatase inhibitor anastrozole (dotted line, n=8). Normal ranges are designated by the thin dotted lines. Values are expressed as means ± standard deviation (SD). *p

Figure 2

Serum insulin (A) and glucose (B) in eight healthy young men administered the GnRH antagonist acyline and placebo testosterone gel and placebo anastrozole. Note the preservation of normal glucose concentrations by the significantly increased concentrations of serum insulin. The group mean is depicted in solid black.

Figure 3

Serum adiponectin (A) and leptin (B) over time in healthy young men administered the GnRH antagonist acyline and placebo testosterone (solid line, n=8), acyline and testosterone (broken line, n=6) or acyline, testosterone and the aromatase inhibitor anastrozole (dotted line, n=8). Values are expressed as means ± SD. *p

Figure 3

Serum adiponectin (A) and leptin (B) over time in healthy young men administered the GnRH antagonist acyline and placebo testosterone (solid line, n=8), acyline and testosterone (broken line, n=6) or acyline, testosterone and the aromatase inhibitor anastrozole (dotted line, n=8). Values are expressed as means ± SD. *p