5-Alpha-Reductase Inhibitor for Benign Prostatic Hyperplasia: A Review of Volume-Selected Therapy and Safe Prostate Cancer Detection

Abstract

Benign prostatic hyperplasia (BPH) is a common cause of male lower urinary tract symptoms (LUTS). The value of 5-alpha-reductase inhibitor (5-ARI) therapy depends mainly on prostate enlargement and the risk of progression. Dutasteride, either alone or in fixed-dose combination with tamsulosin, reduces intraprostatic dihydrotestosterone, decreases prostate volume over several months, and lowers the long-term risk of AUR and BPH-related surgery in appropriately selected men. Dutasteride lowers mean prostate-specific antigen (PSA) by approximately 50% after 6 months, which can mask a rise in PSA if one is not careful. Documentation of the pre-treatment PSA, establishment of an on-treatment nadir or baseline, and systematic evaluation of any confirmed rise in PSA are necessary to avoid missing progression of prostate cancer. Large chemoprevention trials reduced the overall detection of prostate cancer but reported small numerical excesses of high-grade tumors, leading to regulatory warnings. Later bias-adjusted analyses, long-term follow-up, systematic reviews, and population cohorts suggest that this signal is mainly related to detection and PSA monitoring rather than to a clear increase in prostate cancer-specific mortality. This article reviews guidelines, regulatory recommendations, trials, and recent observational studies to support a practical framework: reserving dutasteride-based therapy for men with demonstrable enlargement or a high progression risk; documenting baseline PSA, digital rectal examination, and a prostate-size proxy before treatment; establishing a 6-month PSA baseline; and using a rise-from-nadir and magnetic resonance imaging (MRI)-first diagnostic pathways when cancer is suspected. Safe prescribing depends on appropriate patient selection and careful PSA monitoring.