Marked Suppression of Dihydrotestosterone in Men with Benign Prostatic Hyperplasia by Dutasteride, a Dual 5α-Reductase Inhibitor

Dihydrotestosterone (DHT) is the primary metabolite of testosterone in the prostate and skin. Testosterone is converted to DHT by 5α-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 wi...

Full description

Saved in:
Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2004-05, Vol.89 (5), p.2179-2184
Main Authors: Clark, Richard V., Hermann, David J., Cunningham, Glenn R., Wilson, Timothy H., Morrill, Betsy B., Hobbs, Stuart
Format: Article
Language:English
Subjects:
Biological and medical sciences
Endocrinopathies
Feeding. Feeding behavior
Fundamental and applied biological sciences. Psychology
Medical sciences
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Vertebrates: endocrinology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Dihydrotestosterone (DHT) is the primary metabolite of testosterone in the prostate and skin. Testosterone is converted to DHT by 5α-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 5α-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.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2003-030330