title: Acute and short-term chronic testosterone fluctuation effects on glucose homeostasis, insulin sensitivity, and adiponectin: a randomized, double-blind, placebo-controlled, crossover study.
abstract: BACKGROUND
  Low levels of adiponectin and T in men have been shown to predict development of the metabolic syndrome, but the effects of T on glucose metabolism are incompletely understood and may be influenced either directly or indirectly through changes in body composition or in levels of adiponectin.
  
  
  OBJECTIVE
  The aim of the study was to test whether T exerts its effects on glucose metabolism directly or indirectly.
  
  
  METHODS
  In a randomized, double-blind, placebo-controlled, crossover study, 12 healthy young males were studied on four separate occasions. They received GnRH agonist treatment 1 month before 3 of 4 trial days to induce castrate levels of T. On trial days, T gel containing either high or low physiological T dose or placebo was applied to the body. On a fourth trial day, participants constituted their own eugonadal controls.
  
  
  METHODS
  Each study comprised a 5-hour basal period and a 3-hour hyperinsulinemic euglycemic clamp.
  
  
  METHODS
  We measured the effect of acute T on peripheral glucose disposal, total adiponectin and subforms, and other indices of glucose metabolism.
  
  
  RESULTS
  Short-term hypogonadism was associated with increased high molecular weight adiponectin levels (P < .03) and increased oxidative glucose disposal (P = .03) but not total glucose disposal (P = .07). Acute T treatment was an independent suppressor of high molecular weight adiponectin levels (P = .04) but did not affect total glucose disposal (P = .17).
  
  
  CONCLUSIONS
  These data show that T can act through putative fast nongenomic pathways to affect adiponectin levels in humans. The early hypogonadal state is characterized by a marked shift in fuel oxidation from lipids toward glucose, which may rely partly on buffering capabilities of adiponectin.
authors.affiliation: Department of Endocrinology and Internal Medicine and the Medical Research Laboratories (C.H., L.C.G., J.S.C., S.B.P., C.H.G.), Clinical Institute, Aarhus University Hospital, DK-8000 Aarhus C, Denmark; and Department of Clinical Biochemistry and Immunology (D.M.H.), Statens Serum Institut, 2300 Copenhagen S, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Høst
authors.forename: Lars C
authors.initials: LC
authors.lastname: Gormsen
authors.forename: David M
authors.initials: DM
authors.lastname: Hougaard
authors.forename: Jens S
authors.initials: JS
authors.lastname: Christiansen
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.forename: Claus H
authors.initials: CH
authors.lastname: Gravholt
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D015309:Glucose Clamp Technique; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D010919:Placebos; D013739:Testosterone / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D001786:Blood Glucose; D010919:Placebos; D013739:Testosterone