5α-Reductase inhibitor treatment of prostatic diseases: background and practical implications

Abstract

This literature review discusses the theoretical background of 5a-reductase inhibitor (5ARI) treatment and the resulting clinical implications. A Medline-based search for peer-reviewed articles addressing 5ARIs, benign prostatic hyperplasia and prostate cancer was performed. The 5ARIs Finasteride and Dutasteride, which specifically inhibit the production of dihydrotestosterone by acting as competitive inhibitors of 5a-reductase, are clinically well tolerated and represent an effective treatment option for benign prostatic obstruction. Finasteride is the first compound which has a proven efficacy in chemoprevention of prostate cancer. The aim of this review was to elucidate, if there are sufficient data available to point out clinically relevant differences between the drugs. Both compounds achieve a significant reduction of prostate volume, an improvement of symptoms and a lower risk of acute urinary retention. Whether the different pharmacokinetic and pharmacodynamic properties of Finasteride and Dutasteride are of clinical importance cannot be judged at this time.

Geranylated Coumarins From Thai Medicinal Plant Mammea siamensis With Testosterone 5α-Reductase Inhibitory Activity

“…Of the isolated coumarins, mammeasins E (2, 22.6 µM), A (4, 19.0 µM), and B (5, 24.0 µM), kayeassamins E (9, 33.8 µM), F (10, 15.9 µM), and G (11, 17.7 µM), surangin C (13, 5.9 µM), and mammeas A/AA (17, 19.5 µM), E/BB (22, 16.8 µM), and A/AA cyclo F (34, 23.6 µM) were active 5α-reductase inhibitors. Although the intensity of the 5α-reductase inhibitory activity of these coumarins is moderate compared to a positive control having a steroid skeleton finasteride, to the best of our knowledge, there are few reports of the 5α-reductase inhibitors with non-steroidal skeletons (Dörsam and Altwein, 2009;Aggarwal et al, 2010;Chaudhary and Turner, 2010;Wu and Kapoor, 2013). Therefore, these active coumarins may be useful candidates for seed compounds of new non-steroidal 5αreductase inhibitors.…”

Epidemiology of Prostate Cancer

“…Finasteride and dutasteride are effectively used for the treatment of benign prostatic hyperplasia [284-286] and were studied in clinical trials as potential chemopreventive agents.…”

Novel hormonal approaches in prostate cancer

“…Peripheral androgen blockade (PAB), combining antiandrogen monotherapy with a 5α-reductase inhibitor such as fi nasteride or dutasteride, preserves circulating testosterone levels and results in milder side effects compared with CAB or ADT alone [40]. The evidence supporting the combination of an antiandrogen and 5α-reductase inhibitor comes from only nonrandomized phase 2 clinical trials.…”