title: Testosterone with dutasteride, but not anastrazole, improves insulin sensitivity in young obese men: a randomized controlled trial.
abstract: BACKGROUND
  Testosterone (T) administration to men increases T, estradiol (E2), dihydrotestosterone (DHT), and fat-free mass (FFM), and decreases fat mass (FM) but does not consistently improve insulin sensitivity (IS).
  
  
  OBJECTIVE
  The aim of this study was to examine the effects of T administration in obese, nondiabetic men on body composition and IS, and to determine if inhibition (i) of metabolism of T to E2 with anastrazole or to DHT with dutasteride alters these effects.
  
  
  METHODS
  This was a 98-day randomized, double-blind, parallel group, placebo-controlled trial of 57 men, 24-51 year, free T in the lower 25% of normal range (<0.33 nmol/L), body mass index ≥ 30.0 kg/m(2). Subjects were randomized to one of four groups: (i) placebo: gel, pills, and injection; (ii) T/DHT/iE2: T gel, anastrazole, and acyline (gonadotropin releasing-hormone antagonist to suppress endogenous T); (iii) T/iDHT/E2: T gel, dutasteride, and acyline; (iv) T/DHT/E2: T gel, placebo pills, and acyline.
  
  
  METHODS
  Main outcome measures are insulin sensitivity as percent change (%Δ) in glucose disposal rates (GDR) from a two-step euglycemic clamp (GDR1 and 2), and %FM and %FFM by dual X-ray absorptiometry scan.
  
  
  RESULTS
  Insulin Sensitivity: %Δ GDR1 differed across groups (P = 0.02, anova) and was significantly higher in the dutasteride (T/iDHT/E2) compared with the placebo and T gel (T/DHT/E2) groups. %ΔGDR2 was higher in the dutasteride (T/iDHT/E2) compared with the anastrazole (T/DHT/iE2) group. Body Composition: T gel alone (T/DHT/E2) or with dutasteride (T/iDHT/E2) significantly increased %FFM (P < 0.05) and decreased %FM (P < 0.05). There was no change in %FFM or %FM after placebo or anastrazole (T/DHT/iE2).
  
  
  CONCLUSIONS
  The combination of T plus dutasteride improved body composition and IS while T alone improved body composition but not IS, suggesting that when T is administered to men, reduction to DHT attenuates the beneficial effects of aromatization to E2 on IS but not body composition.
authors.affiliation: Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA; University of California, San Diego, CA, USA.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Juang
authors.forename: Susan
authors.initials: S
authors.lastname: Peng
authors.forename: Kambiz
authors.initials: K
authors.lastname: Allehmazedeh
authors.forename: Ansal
authors.initials: A
authors.lastname: Shah
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Coviello
authors.forename: Karen L
authors.initials: KL
authors.lastname: Herbst
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000008:administration & dosage*; D015502:Absorptiometry, Photon; D000328:Adult; D000077384:Anastrozole; D001378:Azasteroids / Q000008:administration & dosage*; D001823:Body Composition / Q000187:drug effects*; D015992:Body Mass Index; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000494:pharmacology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068538:Dutasteride; D004958:Estradiol / Q000097:blood; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage; D009765:Obesity / Q000378:metabolism*; D013739:Testosterone / Q000008:administration & dosage*; D014230:Triazoles / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D009570:Nitriles; D014230:Triazoles; D013196:Dihydrotestosterone; D000077384:Anastrozole; D013739:Testosterone; D004958:Estradiol; D000068538:Dutasteride
keywords: 5-alpha Reductase; Aromatase; Dihydrotestosterone; Insulin Sensitivity; Obesity; Testosterone