Acute testosterone deprivation reduces insulin sensitivity in men.
Author(s): Rubinow K, Snyder C, Amory J, Hoofnagle A, Page S
Affiliation(s): From the Center for Research in Reproduction and Contraception, Divisions of Metabolism, Endocrinology and Nutrition and General Internal Medicine, Department of Medicine Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington.
Publication date & source: 2011-07-29, Clin Endocrinol (Oxf)., [Epub ahead of print]
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. Copyright (c) 2011 Blackwell Publishing Ltd.