The Benefits of Dual Inhibition of 5α Reductase

In humans, androgens balance cell proliferation and apoptosis, ensuring normal growth and development of the prostate, but also driving pathologic gland enlargement in benign prostatic hyperplasia (BPH) and prostate cancer. The two main androgens are testosterone and dihydrotestosterone (DHT). Reducing testosterone levels results in significant sexual side-effects, whereas reducing DHT does not result in any major safety or tolerability issues. DHT is synthesised from testosterone by the 5α-reductase enzyme, of which there are two isozymes, type I and type II. Expression of both of these isozymes is increased in BPH. Two 5α-reductase inhibitors (5ARIs) are available for BPH management; the dual inhibitor dutasteride inhibits type I and type II 5α reductase, whereas finasteride inhibits only the type II isoenzyme. Pharmacologic studies indicate that the dual 5ARI dutasteride results in greater suppression of DHT than the type II inhibitor. A phase 2, double-blind, placebo-controlled study conducted in men with BPH demonstrated that maximal DHT suppression is achieved in a larger proportion of patients with dutasteride than with finasteride. Dutasteride demonstrates sustained improvement in symptom score and maximal flow rate with no increase in prostate volume up to 4 yr.