Finasteride reduced symptoms in men with benign prostatic hyperplasia
ACP J Club. 1993 Mar-April;118:46. doi:10.7326/ACPJC-1993-118-2-046
Gormley GJ, Stoner E, Bruskewitz RC, et al. The effect of finasteride in men with benign prostatic hyperplasia. N Engl J Med. Oct
To determine the effectiveness of finasteride (1 mg/d and 5 mg/d) for decreasing prostate size, improving urinary flow, and reducing symptoms in men with benign prostatic hyperplasia.
1-year, randomized, double-blind, placebo-controlled trial.
30 clinical centers in North America.
895 men (age range 40 to 83 y) with symptoms of urinary obstruction, an enlarged prostate gland, maximal urinary-flow rates of < 15 mL/s, and a voided volume of ≥ 150 mL. Exclusion criteria were a residual urinary volume of > 350 mL, prostate-specific antigen concentration of ≥ 40 µg/L, or evidence of prostatic cancer, urinary tract infection, chronic prostatitis, or neurogenic bladder. Follow-up was 99%.
297 men were randomized to receive finasteride, one 5-mg tablet/d; 298, to finasteride, one 1-mg tablet/d; and 300, to placebo.
Main outcome measures
Patients filled out questionnaires and were examined monthly to measure compliance, urinary flow and symptoms, and adverse effects. Laboratory tests were done every 3 months, and prostatic volume was checked after 3, 6, and 12 months.
Withdrawals at 1 year were 13% in the high-dose group, 9% in the low-dose group, and 12% in the placebo group. Using an intention-to-treat analysis, at 1 year, total and nonobstructive-symptom scores were lower for patients in the high-dose finasteride group compared with placebo (P < 0.05 for all comparisons). Obstructive-symptom scores were lower in both finasteride groups (P < 0.05) compared with placebo. Comparing patients in the 5-mg, 1-mg, and placebo groups, the prostate had shrunk 19%, 18%, and 3% of baseline size, respectively (P < 0.001), and maximal urinary flow had increased 1.6, 1.4, and 0.2 mL/s (P < 0.05). Decreased libido (5%, 6%, and 1%, respectively) and ejaculatory disorders (4%, 4%, and 2%) occurred more often with finasteride. More patients taking low-dose finasteride reported impotence (3%, 5%, and 2%, respectively). The groups did not differ for other side effects or for prostate cancer and surgery. Finasteride changed blood hormone levels (lower dihydrotestosterone and slightly higher serum testosterone and luteinizing hormone).
Finasteride for benign prostatic hyperplasia appeared to reduce urinary symptoms, increase urinary flow, and decrease prostate size, with the largest effect in the high-dose group. Risk for sexual dysfunction was approximately 3% above that of placebo.
Source of funding: Merck Research Laboratories.
For article reprint: Dr. G.J. Gormley, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA. FAX 215-328-2434.
*Information supplied by author
Traditionally, men with uncomplicated benign prostatic hyperplasia have been managed with prostatectomy or "watchful waiting." Recently, less invasive treatments, including balloon dilation, α-blockers, and finasteride, have been used in everyday practice. These treatments appear to be less effective than prostatectomy, but patients may prefer them because they have fewer adverse effects. Unfortunately, few well-designed trials have been available to guide selection among these options.
Gormley and colleagues are to be congratulated for doing the largest clinical trial of a benign prostatic hyperplasia treatment. Finasteride, a 5-α reductase inhibitor, moderately reduced prostate size over 1 year. The absolute improvements in peak urinary flow and symptom score were, however, relatively small. The overall consistency of the results mitigate methodologic concerns about the multiple statistical comparisons made.
The message for clinicians is not so clear. The data presented do not allow an assessment of the clinical significance of the improvements seen with high-dose finasteride. The trial presents no evidence that finasteride reduces the long-term risk for benign prostatic hyperplasia complications. Whereas the benefits of finasteride are clearly less than those of prostatectomy, comparisons with other less invasive treatments are not possible. Although sexual adverse effects appear to be relatively infrequent over 1 year, long-term adverse effects are undefined. Concerns have been raised about the effect of finasteride on prostate-specific antigen interfering with prostate cancer detection, but there is no evidence that the information value of prostate-specific antigen is actually reduced or even that any delays in detection would increase cancer mortality. For now, clinicians can offer finasteride to men such as those enrolled in this study with confidence that it is better than placebo but not without questions about long-term outcomes that also plague other benign prostatic hyperplasia treatments.
Michael J. Barry, MD
Harvard Medical School Boston, Massachusetts, USA