Efficacy and safety of dutasteride in the four-year treatment of men with benign prostatic hyperplasia.
OBJECTIVE
To assess the long-term safety and efficacy of dutasteride, a dual type 1 and type 2 5-alpha-reductase inhibitor, in the treatment of symptomatic benign prostatic hyperplasia and associated lower urinary tract symptoms.


METHODS
Data from two Phase IIIa multicenter, randomized, placebo-controlled trials of 2-year duration plus a 2-year open-label extension were pooled and analyzed. The entry criteria included age 50 years old or older, clinical diagnosis of benign prostatic hyperplasia, prostate volume of 30 cm3 or greater, American Urological Association symptom score of 12 or greater, peak urinary flow rate of 15 mL/s or less, and prostate-specific antigen level of 1.5 ng/mL or greater but less than 10 ng/mL.


RESULTS
A total of 2802 men were randomized into the double-blind phase of the two studies with 1908 patients (68%) completing the study. Of these, 1570 subjects were enrolled in the open-label phase, and 569 subjects received dutasteride for 48 months. Changes at the 48-month visit for dutasteride/dutasteride-treated subjects included improvement in prostate volume (-26.2%), American Urological Association Symptom Index (-6.1 points), and peak urinary flow rate (+2.8 mL/s). Changes for the placebo/dutasteride group included prostate volume (-20.7%), American Urological Association Symptom Index (-5.3 points), and peak urinary flow rate (+1.8 mL/s). Acute urinary retention and surgery occurred in a small percentage of subjects (less than 2% and less than 1%) in the open-label extension phase. Dutasteride was well tolerated with no statistically significant increase in drug-related adverse events during the open-label extension and no adverse laboratory trends.


CONCLUSIONS
Dual inhibition of 5-alpha-reductase with dutasteride provided sustained efficacy in subjects with symptomatic benign prostatic hyperplasia treated for 48 months. Near-complete, long-term suppression of dihydrotestosterone (93% at 48 months) with dutasteride did not lead to an increase in adverse events compared with that reported in the 2-year period.
Roehrborn
Claus G
CG
Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9110, USA.
Marks
Leonard S
LS
Fenter
Tom
T
Freedman
Sheldon
S
Tuttle
John
J
Gittleman
Marc
M
Morrill
Betsy
B
Wolford
Eric T
ET
D058891:5-alpha Reductase Inhibitors; D000368:Aged; D001378:Azasteroids / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D000068538:Dutasteride; D004542:Ejaculation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D007172:Erectile Dysfunction / Q000139:chemically induced; D006177:Gynecomastia / Q000139:chemically induced; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011467:Prostate / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011470:Prostatic Hyperplasia / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D020018:Sexual Dysfunctions, Psychological / Q000139:chemically induced; D016896:Treatment Outcome; D014463:Ultrasonography; D014563:Urodynamics / Q000502:physiology
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010919:Placebos; D017430:Prostate-Specific Antigen; D000068538:Dutasteride