Health and Prostate

Treating Benign Prostatic Hyperplasia with Finasteride

The androgens testosterone and dihydrotestosterone (DHT) control the development and function of the prostate gland. Testosterone is converted to DHT – the active androgen in many tissues, including prostate and skin – by the enzyme 5-alpha-reductase. Inhibiting 5-alpha-reductase markedly reduces prostate dihydrotestosterone, which decreases the size of the prostate in men with benign prostatic hyperplasia and improves urine flow. There are several 5-alpha-reductase inhibitors in clinical trial, one of which – finasteride (Proscar/Merck) – is approved in the United States for benign prostatic hyperplasia. There are two types of 5-alpha-reductase, and they are produced from different genes on different chromosomes and have different structures (there is only a 50% homology in amino acid sequence). Type 1 is found in all skin; type 2 is found mainly in genital skin. Finasteride blocks primarily type 2. It does not bind the androgen receptor, does not block other steroid hormones, and has no other hormonal effects.

With the recommended dosage of 5 mg once daily, finasteride reduces prostatic dihydrotestosterone by about 90%. The drug has a long biological half-life; DHT may not return to baseline for 2 weeks after finasteride is discontinued. Serum half-life is short by comparison (8 hours in elderly men and 6 hours in middle-aged men). Finasteride reduces semen volume by 25%, but has no effect on sperm count, motility, or morphology. The drug also reduces prostate-specific antigen by 50% in men with BPH within 3 months of initiating therapy. It appears to reduce prostate-specific antigen in men with prostate cancer, which raises concerns about whether finasteride may mask prostate cancer. The drug is excreted in urine and feces; no dosage reduction is necessary in elderly patients or in those with renal failure.

In a large clinical trial involving 895 men with benign prostatic hyperplasia treated for 1 year with finasteride (1 mg or 5 mg) or with placebo, prostate volume decreased by 18% and 19% in the 1-mg and 5-mg finasteride groups, respectively, while urinary flow increased by 22 to 23%. Overall symptoms improved in all three groups, but improvement was significant only in the 5-mg group. Merck recently won approval for labeling changes for finasteride to indicate that the drug works faster and in a greater percentage of patients than was previously thought. (Rittmaster RS. N Engl J Med. 1994;330:120-125. Additional information is available from the manufacturer.)

Treating Benign Prostatic Hyperplasia with Alpha1-blockers

Alpha1-adrenergic blocking agents were developed for the treatment of hypertension, but were found to relieve the symptoms of benign prostatic hyperplasia by relaxing muscles in the bladder and prostate. The first alpha1-blocker to receive FDA approval for benign prostatic hyperplasia was terazosin (Hytrin/Abbott), followed more recently by doxazosin (Cardura/Pfizer). Both drugs provide long- lasting relief of symptoms. In clinical studies of doxazosin involving more than 900 patients with BPH, the drug was significantly superior to placebo for improving symptoms and urinary flow rate. Relief was seen as early as 1 week after the initiation of therapy and was maintained for up to 2 years. In terazosin trials, the drug improved obstructive and irritative symptoms by more than 50% in 1483 men with benign prostatic hyperplasia.

Recently, a report was released describing a study of terazosin in 2,084 men (aged 55 and over) with severe benign prostatic hyperplasia, which is usually treated with surgery. The men were randomized to receive either terazosin (1053 men) or placebo (1031 men) and followed for one year. On average, symptom severity and quality of life were the same in both groups before treatment, but symptoms improved by 38% in patients in the terazosin group compared with 18% in the placebo group. Terazosin produced a 21% improvement in urinary flow compared to 7% with placebo. More patients withdrew from the placebo group because of lack of efficacy (25% withdrawal rate, compared with 11% in the terazosin group), but more withdrew from the terazosin group as the result of side effects (16%, compared with 11% in the placebo group). The most common side effects were dizziness and weakness.

Overall, improvement on terazosin was twice that with placebo. Although terazosin is usually prescribed for patients with moderate benign prostatic hyperplasia, results of this study suggest that drug therapy is an effective alternative to surgery for patients with severe BPH. The drug should also be considered for men with benign prostatic hyperplasia who have hypertension or are at risk for heart attack. A separate analysis of the data showed that 10 of 1031 men in the placebo group suffered heart attacks during the year of the study, compared with just one of 1053 men in the terazosin group. (Annual Meeting of the American Urological Association in Las Vegas, 1996.)