Dihydrotestosterone and the Concept of 5-Alpha-Reductase Inhibition in Human Benign Prostatic Hyperplasia

The document discusses the role of dihydrotestosterone (DHT) in human benign prostatic hyperplasia (BPH) and the use of 5alpha-reductase inhibitors, such as finasteride, in its treatment. DHT, which is not elevated in BPH but remains at normal levels in the prostate with aging, is produced from testosterone by two isoenzymes of 5alpha-reductase, with type 2 being dominant in the prostate. Finasteride, which primarily inhibits type 2 5alpha-reductase, reduces serum DHT by about 70% and prostate DHT by 85-90%. However, dual inhibitors like GI198745 may offer more effective suppression of DHT. Two large international multicenter phase III trials have shown finasteride to be safe and effective for BPH treatment over 12 months, with noncontrolled extensions up to 5 years indicating long-term benefits such as reduced risk of acute urinary retention or surgery, especially in men with large prostates. Further clinical evaluation of dual inhibitors could clarify the roles of type 1 and 2 5alpha-reductase in BPH and other androgen-dependent diseases.