5α-reductase inhibitors in benign prostatic hyperplasia and prostate cancer risk reduction

Androgens play a key role in the development and maintenance of normal and aberrant prostatic growth. It is now understood that DHT is the primary androgen in the prostate; DHT is synthesized from testosterone under the catalysis of the 5α-reductase isoenzymes. Inhibition of these isoenzymes therefore represents a rational approach for the development of pharmacological therapy for BPH and prostate cancer. This led to the discovery and clinical development of first finasteride, a type-2 5ARI, and subsequently dutasteride, a dual 5ARI. Both compounds have demonstrated benefits in the treatment of symptomatic BPH and in the prevention of long-term disease progression. Both agents are safe and well tolerated, and are therefore suitable for long-term clinical use. Finasteride has also demonstrated efficacy in the primary risk reduction of prostate cancer, while the ongoing REDUCE study is evaluating the effects of dutasteride in a similar setting, but with a different risk profile. The effect of dutasteride in reducing progression in low-risk, localized prostate cancer is also being investigated in the ongoing REDEEM study. Given that type-1 5α-reductase appears to play a role in the development and progression of prostate cancer, these ongoing studies will add much to our understanding of dual 5α-reductase inhibition in the prostate cancer setting.

Conflict of interest

Dr Rittmaster is an employee of GlaxoSmithKline.