A review of the clinical efficacy and safety of 5α-reductase inhibitors for the enlarged prostate

Background:Enlargement of the prostate is common among aging men, with an incidence of 90% by the age of 85 years. It is a progressive condition, with growth in prostate size accompanied by lower urinary tract symptoms that can result in long-term complications (eg, acute urinary retention [AUR], need for enlarged prostate-related surgery). Current pharmacologic treatment options include α-blockers (alfuzosin, doxazosin, tamsulosin, and terazosin) and 5α-reductase inhibitors (5ARIs) (finasteride and dutasteride).Objectives:This article reviews the natural history of enlarged prostate and the data supporting management of this condition with α-blocker and 5ARI therapy, either as monotherapy or combination therapy, for symptomatic relief and a reduction in long-term disease progression.Methods:Pertinent English-language articles were identified through a search of MEDLINE (1966-week 2, May 2006) using such search terms as 5α-reductase inhibitor, α-blocker, benign prostatic hyperplasia, dutasteride, efficacy, enlarged prostate, finasteride, and safety.Results:Clinical trials of α-blockers in men with enlarged prostate have reported improvements in total symptom scores of 10% to 20% compared with placebo; however, these agents were not shown to reduce the risk of long-term complications or disease progression. Studies of the 5ARIs have reported significant reductions compared with placebo in the relative risk for AUR and enlarged prostate-related surgery, slowing of disease progression, and relief of symptoms. In studies of dutasteride, improvements in symptom scores were greater after 4 years of therapy compared with 2 years (−6.4 vs −4.3 points, respectively) and flow rates were better (2.6 vs 2.3 mL/sec). Six-year data for finasteride showed maintenance of the decreased risk for AUR and enlarged prostate-related surgery. Use of combination therapy with an α-blocker and a 5ARI may be of benefit in patients who require immediate relief of symptoms, with discontinuation of the α-blocker after several months of therapy. 5ARIs were generally well tolerated, with sexual dysfunction the most frequently reported adverse effect, although in only a small proportion of men (1%–8%).Conclusions:The use of 5ARI therapy is a rational approach to symptom management and prevention of long-term negative outcomes in men with enlarged prostates.V 3