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Therapeutics

Terazosin reduced BPH symptoms and finasteride did not

ACP J Club. 1997 Jan-Feb;126:15. doi:10.7326/ACPJC-1997-126-1-015


Source Citation

Lepor H, Williford WO, Barry MJ, et al., for the Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. N Engl J Med. 1996 Aug 22;335:533-9.


Abstract

Objective

To determine whether terazosin, finasteride, or both are safe and effective for men with benign prostatic hyperplasia (BPH).

Design

1-year, randomized, double-blind, placebo-controlled trial.

Setting

U.S. Veterans Affairs medical centers.

Patients

1229 men who were 40 to 80 years old (mean age 65 y) and had symptomatic BPH. Inclusion criteria were scores of ≥ 8 on the American Urological Association (AUA) Symptom Index, a mean peak urinary-flow rate of ≤ 15 mL/s, and a minimal residual volume after voiding of 125 mL. Exclusion criteria were use of many medications, including the study drugs, α-blockers, β-blockers, and antiandrogen drugs, or numerous medical conditions.

Intervention

After a 4-week run-in period, men were allocated to placebo (n = 305); finasteride, 5 mg/d at bedtime (n = 310); terazosin, 15 mg/d (n = 305); or both (n = 309). The terazosin dose was titrated from 1 mg at day 1 to 15 mg by day 15. Follow-up was 82%.

Main outcome measures

AUA symptom scores and peak urinary-flow rates.

Main results

Analysis was by intention to treat. Compliance ranged from 94% to 98% at 1 year, and symptom scores were lower (improved) in the terazosin and the combination groups compared with the finasteride and placebo groups (P < 0.001 for all comparisons except terazosin vs combination, P = 1.00, and finasteride vs placebo, P = 0.63). Symptom scores improved in the first 13 weeks and then remained stable. Peak urinary-flow rates increased more in the terazosin group (by 2.7 mL/s) and the combination group (by 2.3 mL/s) than in the finasteride group (by 1.6 mL/s) and the placebo group (by 1.6 mL/s) (P < 0.001 for all comparisons except terazosin vs combination, P = 0.15, and finasteride vs placebo, P = 0.07). The increases in peak urinary-flow rates occurred by week 4, and the rates stayed stable thereafter. Dizziness and pos-tural hypotension were increased in the terazosin and combination groups (P < 0.001), impotence was increased in the finasteride and combination groups (P = 0.05), ejaculatory abnormality was increased in the combination group (P < 0.001), and decreased libido occurred in the finasteride and combination groups (P = 0.05).

Conclusions

Terazosin was more effective than placebo for reducing symptoms and increasing peak urinary-flow rates in men with benign prostate hyperplasia; finasteride was not. The combination of terazosin and finasteride was no more effective than terazosin alone.

Sources of funding: Department of Veteran Affairs Medical Research Service; Merck and Company; Abbott Laboratories.

For article reprint: Dr. H. Lepor, Department of Urology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA. FAX 212-263-6303.


Commentary

Drug treatment is an attractive alternative to surgery for patients with symptoms of BPH. Several clinical trials have shown that long-acting α1-adrenergic blockers and finasteride, a 5α-reductase inhibitor, are modestly effective in relieving the symptoms of BPH.

In this randomized controlled trial, Lepor and colleagues compared the α1-adrenergic blocking agent terazosin with finasteride alone, a terazosin-finasteride combination, and placebo. The study appears to be valid: Patients and providers were blinded to treatment allocations, the baseline characteristics of all 4 groups were similar, compliance was excellent, few losses to follow-up occurred throughout the 1-year study, and the patients were analyzed in the groups to which they were assigned (intention-to-treat analysis). The outcomes (symptom scores and urinary-flow rates) are clinically relevant, but it would have been helpful if the authors had included information on improvement in residual volumes after voiding, which can be easily ascertained in an office practice.

The improvements seen with terazosin alone were modest, but finasteride was no better than placebo in relieving symptoms or increasing urinary-flow rates. With the exception of dizziness and postural hypo-tension, the side effects of terazosin were mild. Men receiving finasteride were more likely to report sexual dysfunction. A global assessment would have been helpful in showing whether patients considered the benefits of the treatment to outweigh the side effects.

Random variation could easily explain the apparent discrepancy between the lack of benefit from finasteride in this study and the small improvement in symptoms and urinary-flow rates seen among men receiving finasteride in the multicenter study reported in 1992 (1). Our approach is to start men with symptomatic BPH on therapy with an α1-blocker. We recommend surgery instead of adding finasteride if our patients' symptoms and residual volumes after voiding are not sufficiently alleviated by single-agent therapy.

Peter S. Millard, MD, PhD
William J. Meinert Jr, MDEastern Maine Medical CenterBangor, Maine, USA


Reference

1. Gormley GJ, Stoner E, Bruskewitz RC, et al. The effect of finasteride in men with benign prostatic hyperplasia. N Engl J Med. 1992;327:1185-91.