The clinical applications of five-alpha reductase inhibitors

INTRODUCTION Five-alpha reductase (5-AR) deficiency was first identified by Imperato-McGinley and Walsh as the cause of pseudohermaphroditism in two separate studies. The discoveries led to the development of finasteride (inhibitor of type 2 isoenzyme of 5-AR) and dutasteride (inhibitor of type 1 and type 2 isoenzymes of 5-AR. Both drugs have been proven effective for the treatment of benign prostatic hyperplasia and improve voiding symptoms, reduce the risk of urinary retention and the need for prostate surgery. Five-alpha reductase inhibitors 5-ARIs have been demonstrated to be chemopreventive agents and reduce the risk of prostate cancer, although the risk of selecting out or mediating higher grade prostate cancer remains uncertain. A lower dose of finasteride has been shown to be effective in the treatment of male pattern baldness.

A Medline search was performed using mesh terms, benign prostatic hypertrophy, prostate cancer, male pattern baldness, female and 5-AR.

The Prostate Long Term Efficacy and Safety Study (PLESS) was a randomized double-blind study that established that finasteride resulted in a 22% increase in maximum flow rate and a 19% decrease in prostate volume. Further studies demonstrated that finasteride caused a significant reduction in the risk of the need for surgery and urinary retention in a 4 year period. Additional studies showed similar beneficial results with dutasteride. The potential benefits of 5-ARIs as chemopreventive agents were examined in the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) studies. In the 7 year PCPT trial, 18.4% of the finasteride group developed prostate cancer compared to 24.4% in the placebo group. In the 4 year REDUCE trial, there was a 22.8% reduction of prostate cancer at the conclusion of the study. Despite the reduction of prostate cancer in both the PCPT and REDUCE trials, each study showed an increased risk of prostate cancer in the treatment arms. The explanation for these observations remains an area of investigation. Low dose finasteride has also been used successfully for the treatment of male pattern baldness.

The use of 5-ARIs has been a major advance in urologic clinical practice. Urologists should be familiar with the underlying pharmacology of 5-ARIs as well as the clinical indications for their use.