The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme?

Abstract

Normal growth and function of the prostate are contingent on the reduction of testosterone to dihydrotestosterone (DHT) by 5-alpha reductase (5-AR) enzymes types 1 and 2. It has been theorized that an overabundance of DHT may be implicated in the pathogenesis of both benign prostatic hyperplasia (BPH) and prostate cancer. Inhibitors of 5-AR such as dutasteride and finasteride may therefore have an important role in the prevention and treatment of BPH and prostate cancer. Dutasteride provides greater suppression of DHT than finasteride, thereby underlying the hypothesis that inhibition of both type 1 and type 2 would provide correspondingly greater protection than inhibition of type 2 alone. We review the potential significance of the 5-AR inhibitors in reducing the risk of prostate cancer according to the basic biology of prostate disease.

Fig. 1.

Mean area of moderate- to high-intensity staining, as a percentage of total epithelial or tumour area, for 5-AR1 and 5-AR2 in benign prostatic hyperplasia (BPH), benign tissues adjacent to cancer (Adj. Ben.), and low-, moderate- or high-grade cancer. Reproduced with permission from the Journal of Urology.

Fig. 2.

Dual 5-alpha reductase inhibition results in greater serum dihydrotestosterone (DHT) suppression. Percentage changes from baseline in DHT over time are shown as arithmetic means. Data were derived from the Journal of Clinical Endocrinology and Metabolism.