Conclusions Oral TRT produces significant CV risk .
Differences in the degree to which serum DHT is elevated may underlie the varying CV risk by TRT administration route , as elevated serum dihydrotestosterone has been shown to be associated with CV risk in observational studies
Background Potential cardiovascular ( CV ) risks of testosterone replacement therapy ( TRT ) are currently a topic of intense interest .
However , no studies have addressed CV risk as a function of the route of administration of TRT .
Testosterone with dutasteride, but not anastrazole, improves insulin sensitivity in young obese men: a randomized controlled trial.
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 r and omized , 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 r and omized 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
Conclusions Oral TRT produces significant CV risk .
Differences in the degree to which serum DHT is elevated may underlie the varying CV risk by TRT administration route , as elevated serum dihydrotestosterone has been shown to be associated with CV risk in observational studies
Background Potential cardiovascular ( CV ) risks of testosterone replacement therapy ( TRT ) are currently a topic of intense interest .
However , no studies have addressed CV risk as a function of the route of administration of TRT .