Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia.
OBJECTIVE
We reviewed the physiological and pathogenic role of dihydrotestosterone (DHT), evidence for the beneficial effects of decreasing DHT through 5alpha-reductase inhibition and the effects of altering the androgen balance with these agents.


METHODS
A review of the relevant literature was done using published studies identified from the MEDLINE database.


RESULTS
The androgens DHT and testosterone have complementary roles in male physiology. Each is mediated through the intracellular androgen receptor. It has been hypothesized that DHT may provide an amplification mechanism for testosterone, which could be a beneficial adaptation in men with low circulating testosterone. The recognition of the central role of DHT in benign prostatic hyperplasia (BPH) has changed the way the disease is viewed and has led to the introduction of 5alpha-reductase inhibitors, which can prevent and retard the progression of BPH by suppressing DHT synthesis. The 5alpha-reductase inhibitors decrease prostate volume. In doing so they improve symptoms and urinary flow, and decrease the risks of acute urinary retention and the need for BPH related surgery. The predominant drug related adverse events with 5alpha-reductase inhibitors are reproductive events, that is typically decreased libido, impotence and ejaculatory dysfunction. These events occur in a minority of men and tend to decrease with a longer treatment duration.


CONCLUSIONS
DHT appears to have an obligatory role in the development of BPH. The role of 5alpha-reductase inhibitors in the treatment of BPH has been firmly established with an adverse events profile that is suitable for long-term use.
Andriole
Gerald
G
Division of Urological Surgery, Washington University in St. Louis, St. Louis, Missouri 63110, USA.
Bruchovsky
Nicholas
N
Chung
Leland W K
LW
Matsumoto
Alvin M
AM
Rittmaster
Roger
R
Roehrborn
Claus
C
Russell
David
D
Tindall
Donald
D
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D013196:Dihydrotestosterone / Q000037:antagonists & inhibitors* / Q000097:blood; D000068538:Dutasteride; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018120:Finasteride / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000201:enzymology; D016896:Treatment Outcome; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000201:enzymology
D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D004791:Enzyme Inhibitors; D013196:Dihydrotestosterone; D018120:Finasteride; D000068538:Dutasteride