Benign prostatic hyperplasia is an androgen-dependent disease which afflicts a large percentage of males over the age of fifty, and is usually treated by surgery. Dihydrotestosterone, a 5 alpha-reduced metabolite of testosterone, has been implicated as a causative factor in the progression of the disease, largely through the clinical study of males who are genetically deficient in the dihydrotestosterone-producing enzyme, steroid 5 alpha-reductase. As a result, inhibition of this enzyme has become a pharmacological strategy for the treatment of benign prostatic hyperplasia as well as other dihydrotestosterone-related disorders such as acne and male pattern baldness. In this review, Brian Metcalf and colleagues focus on the chemical and kinetic mechanisms of steroid 5 alpha-reductase, and known inhibitors of this enzyme, and discuss the rationale behind the design of a mechanistically distinct class of steroid 5 alpha-reductase inhibitors.
Metcalf BW, Levy MA, Holt DA