Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia.
Level 5 - mechanism / opinion, no new human data
Narrative review of physiology and previously published trial evidence
PubMed 12022710 · doi:10.1007/s00345-002-0248-5
What was done
This narrative review synthesizes the role of dihydrotestosterone (DHT) and 5alpha-reductase isoenzymes in benign prostatic hyperplasia (BPH). It discusses mechanism and clinical findings from two large multicentre phase III trials (12 months of randomized controlled data plus uncontrolled extensions up to 5 years) and a meta-analysis of six randomized clinical trials of finasteride, as well as data on the dual type 1 and 2 inhibitor GI198745.
What was found
Finasteride suppresses serum DHT by approximately 70% and intraprostatic DHT by 85% to 90%. Suppression of both type 1 and 2 isoenzymes with GI198745 yields greater and more consistent serum DHT reduction than selective type 2 inhibition. Long-term finasteride reduced acute urinary retention and surgical intervention, showing the highest efficacy in men with enlarged prostates.
Why it matters
The paper outlines the pharmacological rationale for dual 5alpha-reductase inhibition, highlighting that suppressing both isoenzymes may provide clinical advantages over selective type 2 blockade in BPH.
Limits
The abstract describes a narrative review rather than a systematic review or primary study, providing no overall sample size (n) or exact numerical risk reductions for clinical endpoints. Head-to-head clinical trial data between dual and selective inhibitors were not yet available.
Cited by
- contradicts Finasteride inhibits two of the three 5-alpha reductase isoenzymes, resulting in approximately 60 to 70% inhibition of systemic DHT.