title: 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.
  
  
  METHODS
  Placebo-controlled, randomized trial.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: K B
authors.initials: KB
authors.lastname: Rubinow
authors.forename: C N
authors.initials: CN
authors.lastname: Snyder
authors.forename: J K
authors.initials: JK
authors.lastname: Amory
authors.forename: A N
authors.initials: AN
authors.lastname: Hoofnagle
authors.forename: S T
authors.initials: ST
authors.lastname: Page
mesh_terms: D054392:Adipokines / Q000097:blood; D000293:Adolescent; D000328:Adult; D018932:Chemokine CCL2 / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000494:pharmacology; D054839:Retinol-Binding Proteins, Plasma / Q000032:analysis; D013739:Testosterone / Q000097:blood / Q000502:physiology*
chemical_list: D054392:Adipokines; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007328:Insulin; D009842:Oligopeptides; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D013739:Testosterone; C109238:acyline