The effect of dutasteride on intraprostatic dihydrotestosterone concentrations in men with benign prostatic hyperplasia.
The dual 5alpha-reductase inhibitor, dutasteride has been shown to suppress serum dihydrotestosterone (DHT) by >90%. In the present study, the effect of dutasteride 0.5 mg/day on intraprostatic DHT levels was investigated. In this multicenter, double-blind trial, 43 men with benign prostatic hyperplasia (BPH) scheduled to undergo transurethral resection of the prostate (TURP) were randomized to receive dutasteride, 0.5 mg/day or placebo for 3 months before surgery. Intraprostatic DHT, testosterone and dutasteride levels were determined at the time of TURP. Changes in serum DHT and testosterone from baseline, and both serum and intraprostatic dutasteride levels at the time of TURP were also assessed. Dutasteride reduced intraprostatic DHT by 94% relative to placebo (P<0.001); the adjusted mean intraprostatic DHT concentration was 3.23 and 0.209 ng/g in the placebo and dutasteride groups, respectively. In the dutasteride group, serum DHT was reduced from baseline by 93% at month 3, a significantly greater reduction (P<0.001) than the 15% decrease observed in the placebo group. There was a reciprocal increase in intraprostatic testosterone but the level of intraprostatic testosterone in the dutasteride group tended to be lower than the intraprostatic DHT level in the placebo group (P=0.06). Significant intraprostatic DHT suppression was achieved in all subjects who received dutasteride, regardless of the level of intraprostatic dutasteride. There was a strong positive correlation between serum and intraprostatic dutasteride concentrations (R(2)=0.73). After 3 months of treatment, dutasteride 0.5 mg/day provided near-complete suppression of both intraprostatic and serum DHT in men with BPH.
Wurzel
R
R
Department of Urology, Grove Hill Medical Center, New Britain, CT 06052, USA. Rwurzel@grovehill.com
Ray
P
P
Major-Walker
K
K
Shannon
J
J
Rittmaster
R
R
D000368:Aged; D001378:Azasteroids / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013196:Dihydrotestosterone / Q000097:blood / Q000378:metabolism*; D004311:Double-Blind Method; D000068538:Dutasteride; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000187:drug effects / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D013739:Testosterone / Q000378:metabolism
D001378:Azasteroids; D013196:Dihydrotestosterone; D013739:Testosterone; D000068538:Dutasteride