The role of dihydrotestosterone in benign prostatic hyperplasia

Abstract

This article examines the role of the androgen dihydrotestosterone (DHT) in the healthy and diseased prostate and considers the implications of the data on DHT for therapeutic approaches to benign prostatic hyperplasia (BPH). Development and maintenance of the normal prostate, as well as development of BPH, depend on a functional androgen-signaling axis, components of which include: (1) testosterone synthesis in the testes and adrenal glands; (2) conversion of testosterone to DHT; (3) transport of DHT to target tissues; and (4) binding of DHT to the androgen receptor with consequent modulation of genes. DHT plays a beneficial role in the developing prostate but it can be detrimental in the adult prostate in that it causes pathologic prostate growth. The role of DHT in other adult tissues is uncertain. DHT has not been shown to perform beneficial functions unique from testosterone in the adult male, and it is believed that its fundamental effect is to amplify testosterone's weaker hormonal signal. Increased understanding of the cellular mechanisms by which the androgen-signaling axis functions has led to advances in treatment for prostate disease. In BPH, the 5alpha-reductase inhibitors--the only class of therapy to act at the pathophysiologic substrate of the disease--arrest the disease process, reduce prostate volume, improve symptoms, and reduce the risk of acute urinary retention and BPH-related surgery. The availability of dutasteride, the first dual (Type 1/Type 2) 5alpha-reductase inhibitor, offers the opportunity for rapid and consistent inhibition of DHT.