Finasteride reduced symptoms and need for surgery for benign prostatic hyperplasia
ACP J Club. 1998 Jul-Aug;129:11. doi:10.7326/ACPJC-1998-129-1-011
McConnell JD, Bruskewitz R, Walsh P, et al., for the Finasteride Long-Term Efficacy and Safety Group. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. N Engl J Med. 1998 Feb 26;338:557-63.
Among men with benign prostatic hyperplasia (BPH), can finasteride reduce symptoms, development of acute urine retention, and the need for surgery over the long term?
4-year, randomized, double-blind, placebo-controlled trial.
95 study centers.
3040 men (mean age 64 y) who had BPH with moderate to severe lower urinary tract symptoms, decreased maximal urine flow rates, and an enlarged prostate gland. Exclusion criteria were use of α-adrenergic-antagonist drugs or antiandrogens; history of chronic prostatitis, recurrent urinary tract infections, or prostate or bladder cancer or surgery; or a serum prostate-specific antigen concentration ≥ 10 ng/mL. Follow-up was 91%.
After a 1-month run-in period, men were allocated to finasteride, 5 mg/d (n = 1524), or placebo (n = 1516) for 4 years.
Main outcome measures
Main outcome was a symptom score of 0 to 34, based on a self-administered questionnaire about the frequency of symptoms (including nocturia; impairment of size and force of urine stream; urination frequency; delayed, strained, or interrupted urination; and incomplete emptying of the bladder). Secondary outcomes were surgery for BPH and acute urine retention.
Men who received finasteride had greater mean decreases in symptom scores than men who received placebo (2.6 vs 1.0, P < 0.001). Fewer men in the finasteride group had surgery (P < 0.001) or developed acute urine retention (P < 0.001)(Table). The incidence of adverse effects was higher for the finasteride group than for the placebo group for decreased libido (P = 0.002), impotence (P < 0.001), decreased ejaculate volume (P < 0.001), ejaculation disorder (P = 0.002), breast enlargement or tenderness (both P = 0.03), and rash (P = 0.04).
Among men with moderate-to-severe benign prostatic hyperplasia, finasteride reduced symptoms, the need for surgery, and acute urine retention.
Source of funding: Merck.
For correspondence: Dr. J.D. McConnell, University of Texas Southwestern Medical Center, Department of Urology (J8-148), 5323 Harry Hines Boulevard, Dallas, TX 75235-9110, USA. FAX 214-648-3398.
Table. Finasteride vs placebo for benign prostatic hyperplasia*
|Outcomes at 4 years||Finasteride||Placebo||RRR (95% CI)||NNT (CI)|
|Surgery||4.6%||10.1%||54.9% (40.7 to 65.7)||18 (13 to 27)|
|Acute urine retention||2.8%||6.6%||57.9% (40.1 to 70.4)||27 (19 to 43)|
*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
Most patients with bothersome lower urinary tract symptoms try a course of pharmacologic therapy before considering surgery for BPH. The pharmacologic armamentarium includes α-adrenergic blockers (e.g., terazosin, doxazosin, and tamsulosin) and the 5α-reductase inhibitor finasteride. In short-term studies, finasteride has had a modest effect on symptoms for men with enlarged prostates (1); however, in one head-to-head Veterans Affairs trial, an α-blocker provided superior symptom relief across a spectrum of prostate sizes (2).
McConnell and colleagues provide the longest follow-up for any controlled trial of BPH therapy. For a period of 4 years, the superiority of finasteride over placebo for mean symptom reduction among men with large prostates was modest. On the other hand, finasteride resulted in an impressive relative reduction in the rate of prostatectomy and acute urine retention. The former finding is especially interesting, as most prostatectomies are done for symptom relief, and the magnitude of the reduction in surgery seems out of proportion to finasteride's average effect on symptoms.
Whether the numbers needed to treat to prevent these events are acceptable is in the eye of the beholder. Most men would prefer to avoid surgery or urine retention, but neither is particularly risky. As is true for virtually all decision making regarding BPH, informed patients should participate in the choice.
These results will logically lead to cost-effectiveness analyses of finasteride prophylaxis. They also raise the question of whether combination therapy with an α-blocker and finasteride would provide optimal medical management for men with large prostates. Although the Veterans Affairs trial showed no advantage of combination therapy over terazosin alone for symptom relief (2), many of these men had smaller prostates and were followed for only 1 year.
Michael J. Barry, MD
Massachusetts General HospitalBoston, Massachusetts, USA
1. Boyle P, Gould AL, Roehrborn CG. Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology. 1996;48:398-405.
2. Lepor H, Williford WO, Barry MJ, et al. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. N Engl J Med. 1996;335:533-9.