Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor.
Dihydrotestosterone (DHT) is the primary metabolite of testosterone in the prostate and skin. Testosterone is converted to DHT by 5alpha-reductase, which exists in two isoenzyme forms (types 1 and 2). DHT is associated with development of benign prostatic hyperplasia (BPH), and reduction in its level with 5alpha-reductase inhibitors improves the symptoms associated with BPH and reduces the risk of acute urinary retention and prostate surgery. A selective inhibitor of the type 2 isoenzyme (finasteride) has been shown to decrease serum DHT by about 70%. We hypothesized that inhibition of both isoenzymes with the dual inhibitor dutasteride would more effectively suppress serum DHT levels than selective inhibition of only the type 2 isoenzyme. A total of 399 patients with BPH were randomized to receive once-daily dosing for 24 wk of dutasteride (0.01, 0.05, 0.5, 2.5, or 5.0 mg), 5 mg finasteride, or placebo. The mean percent decrease in DHT was 98.4 +/- 1.2% with 5.0 mg dutasteride and 94.7 +/- 3.3% with 0.5 mg dutasteride, significantly lower (P < 0.001) and with less variability than the 70.8 +/- 18.3% suppression observed with 5 mg finasteride. Mean testosterone levels increased but remained in the normal range for all treatment groups. Dutasteride appeared to be well tolerated with an adverse event profile similar to placebo.
Clark
Richard V
RV
Clinical Pharmacology, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA. richard.v.clark@gsk.com
Hermann
David J
DJ
Cunningham
Glenn R
GR
Wilson
Timothy H
TH
Morrill
Betsy B
BB
Hobbs
Stuart
S
D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000728:Androgens / Q000378:metabolism*; D001378:Azasteroids / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D042944:Cholestenone 5 alpha-Reductase / Q000037:antagonists & inhibitors*; D013196:Dihydrotestosterone / Q000037:antagonists & inhibitors* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D000068538:Dutasteride; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood
D000726:Androgen Antagonists; D000728:Androgens; D001378:Azasteroids; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D013739:Testosterone; D007986:Luteinizing Hormone; D042944:Cholestenone 5 alpha-Reductase; D000068538:Dutasteride