Effect of dutasteride on intraprostatic androgen levels in men with benign prostatic hyperplasia or prostate cancer.
OBJECTIVE
Dutasteride exerts its beneficial effects on the prostate through suppression of intraprostatic dihydrotestosterone (DHT). The aim of this analysis was to assess the effects of the approved dose of dutasteride (0.5 mg/d), given for 2 weeks to 4 months, on the serum and intraprostatic DHT and testosterone levels in 3 randomized studies.


METHODS
Intraprostatic androgen levels were measured in benign prostatic tissue collected during transurethral resection of the prostate (benign prostatic hyperplasia studies, n = 256) or radical prostatectomy (prostate cancer study, n = 51), performed after 2 weeks, or 1, 3, or 4 months of treatment with dutasteride or with placebo or surgery alone. The serum androgen levels were assessed at the same points during treatment. Data from the control groups were pooled to provide 1 comparison group.


RESULTS
Dutasteride reduced the intraprostatic DHT levels by 83%, 90%, 92%, and 93% after 2 weeks and 1, 3, and 4 months of treatment, respectively, compared with placebo/surgery alone. Dutasteride reduced the serum DHT levels from baseline by 84% at 2 weeks and by approximately 90% at 1, 2, 3, and 4 months compared with a 5.2% increase in the control group. The decrease in DHT levels with dutasteride was accompanied by a reciprocal increase in the serum and intraprostatic testosterone levels. However, the intraprostatic testosterone levels in the dutasteride groups generally remained lower than the intraprostatic DHT levels in the control group.


CONCLUSIONS
The results of our study have shown that dutasteride provides near-maximal suppression of both serum and intraprostatic DHT levels in men with benign prostatic hyperplasia or prostate cancer at all points assessed.
Rittmaster
Roger
R
Urology Clinical Development and Medical Affairs, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA. roger.s.rittmaster@gsk.com
Hahn
Robert G
RG
Ray
Paul
P
Shannon
Jennifer B
JB
Wurzel
Rafael
R
D000368:Aged; D001378:Azasteroids / Q000494:pharmacology* / Q000627:therapeutic use*; D013196:Dihydrotestosterone / Q000032:analysis* / Q000097:blood; D000068538:Dutasteride; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000737:chemistry* / Q000187:drug effects*; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D013739:Testosterone / Q000032:analysis* / Q000097:blood; D013997:Time Factors
D001378:Azasteroids; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D013739:Testosterone; D000068538:Dutasteride