Testosterone suppression and/or low testosterone may increase insulin resistance in men. - GreenMedInfo Summary

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:  22 healthy male volunteers, 18-55 years old. Methods:  Following screening, subjects received the gonadotropin 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 10g/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 also was apparent in the insulin sensitivity indices HOMA-IR (p=0.03) and QUICKI (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.