Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor

• Published in: The journal of clinical endocrinology and metabolism 2004-05, Vol.89 (5), p.2179
• Main Authors: Clark, Richard V, Hermann, David J, Cunningham, Glenn R, Wilson, Timothy H, Morrill, Betsy B, Hobbs, Stuart
• Format: Article
• Language: English
• Subjects: Androgen Antagonists - administration & dosage; Androgen Antagonists - adverse effects; Androgen Antagonists - blood; Androgen Antagonists - therapeutic use; Androgens - metabolism; Azasteroids - administration & dosage; Azasteroids - adverse effects; Azasteroids - blood; Azasteroids - therapeutic use; Cholestenone 5 alpha-Reductase - antagonists & inhibitors; Dihydrotestosterone - antagonists & inhibitors; Dihydrotestosterone - blood; Dose-Response Relationship, Drug; Dutasteride; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - blood; Enzyme Inhibitors - therapeutic use; Humans; Luteinizing Hormone - blood; Male; Middle Aged; Osmolar Concentration; Prostatic Hyperplasia - drug therapy; Testosterone - blood
• ISSN: 0021-972X

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.