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Testosterone with Dutasteride, but Not Anastrazole, Improves Insulin Sensitivity in Young Obese Men: A Randomized Controlled Trial

Authors


  • Sources of support: This work was funded by UCSD GCRC grant 5M01 RR000827 and NIH NIDDK grant K23 DK 065038-05 (to K.L.H.). Auxilium and GlaxoSmithKline provided research drugs.

Abstract

Introduction

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).

Aim

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/m2. 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.

Main Outcome Measures

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. Juang PS, Peng S, Allehmazedeh K, Shah A, Coviello AD, and Herbst KL. Testosterone with dutasteride, but not anastrazole, improves insulin sensitivity in young obese men: A randomized controlled trial. J Sex Med 2014;11:563–573.

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