Health and Prostate

Lepor H, Williford WO, Barry MJ, Brawer MK, Dixon CU.
The efficacy of terazosin, finasteride or both in benign prostate hyperplasia.
N Engl J Med 1996; 335:533-9.

Research question

There are two main types of medications for the treatment of benign prostate hyperplasia (BPH): the first are α-adrenergic-antagonist drugs (eg, terazosin) that relax the smooth muscle in the prostate and the second are 5-α-reductase inhibitors (eg, finasteride) that block formation of dihydrotestosterone and thereby shrink the prostate. Which works better? Does a combination of the two drugs work best?

Type of article and design

Randomized, controlled trial of therapy.

Relevance to family physicians

In the last few years you could hardly open a medical journal without being bombarded with information about finasteride (Proscar). Many of us were using terazosin (Hytrin) also to treat BPH patients who had symptoms or were tired of “watchful waiting.” Terazosin is cheaper, is covered on most provincial formularies, and works faster, but we often wondered which drug was more effective and whether a combination could be used for treatment-resistant cases to prevent surgery. In the United States in 1990, more than 329000 men had transurethral prostatectomies (TURPs). A TURP is very effective but patients are understandably concerned about the side effects of surgery. Benign prostatic hyperplasia is extremely common and becomes more common with age. It can have a deleterious effect on quality of life, especially in the context of such conditions as chronic disease and depression.

Overview of study and outcomes

This study recruited 1686 men, aged 45 to 80 years, who had symptomatic benign prostate hyperplasia and were seen at Veterans Affairs medical centres. During a 4-week lead-in time, the men received a placebo and were evaluated twice using the American Urological Association’s (AUA) symptom index; to be eligible, men had to score at least 8 points out of 35.

Uroflometry, residual volume after voiding, serum concentrations of prostate-specific antigen (PSA), urine culture and sensitivity, and transrectal ultrasound examinations were all performed. No threshold level of prostatic enlargement was required (which fits with current evidence that severity of BPH is not simply a function of size). Exclusion criteria were use of similar medications to those being tested, symptoms of severe coronary artery disease, orthostatic hypotension, prostate cancer, history of prostate surgery, and active urinary or kidney disease. This left 1229 men (73% of those recruited) who were mostly white, averaged approximately 65 years old, had prostatic volumes of 37 cm³, had PSAs of 2 to 3, and had AUA symptom scores of an average 16 out of 35.

Results

The men at each site, randomized to finasteride, terazosin, combination therapy, or placebo, were evaluated at 2, 4, and 8 weeks and then every 6 weeks for 1 year for AUA symptom scores and peak urinary flow rates. Symptom scores in each of the four groups had decreased at 1 year by 2.6 (placebo), 3.2 (finasteride), 6.1 (terazosin), and 6.2 (combination) points (P < 0.001). Peak urinary flow rates had increased by mean values of 1.4, 1.6, 2.7, and 3.2 mL/sec, respectively (P < 0.001). Adverse effects caused 1.9% of the placebo group, 6.2% of the finasteride group, 7% of the terazosin group, and 9.4% of the combination group to drop out. As expected, dizziness was significantly more frequent in the terazosin group. Impotence and decreased libido were significantly more frequent among finasteride subjects. Combination therapy had these side effects and significantly more ejaculatory abnormalities.

Analysis of methodology

This sophisticated, four-arm, randomized trial had good follow up and compliance. Groups were similar at the start of the trial and were treated equally with intention-to-treat analysis.

Application to clinical practice

This study is interesting in that it tells us that a drug that many physicians are prescribing is no better than placebo.

This conflicts with some previous data, and the editorial accompanying the study tells why: benign prostate hyperplasia is not a homogeneous process and size does not predict symptoms. This study had no threshold size of prostate whereas the previous two studies positive for finasteride were restricted to men with larger prostates (60 mL² and 47 mL², respectively). Given the mechanism of shrinking or debulking with finasteride, those with larger prostates might well do better than they did with placebo.

What is the clinical significance of a 3- to 4-point reduction out of 35 in an AUA symptom score? It might be worthwhile for patients with severe symptoms who are getting up at night repeatedly to urinate, but perhaps not for patients with milder symptoms who wish to avoid the adverse effects of terazosin. Including some patient-oriented outcomes might have been helpful to further assess the benefits of treatment against the adverse effects of medications. Quality-of-life measurements might have been helpful also to assess how lower scores and increased flow allowed better social functioning, especially for elderly or chronically ill men.

Bottom line

Terazosin is probably the first-line drug of choice for benign prostate hyperplasia given its effectiveness, low cost, and rapid action.

Finasteride did no better than placebo in this trial. Patients who are treatment resistant and have large prostates might choose finasteride as a final alternative if they wish to delay surgery. The mixed results of this trial indicate the heterogeneous nature of this disease process and dispel the myth that all symptoms of BPH are simply the result of an enlarging prostate.