The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia.
BACKGROUND
Benign prostatic hyperplasia is commonly treated with alpha-adrenergic-receptor antagonists (alpha-blockers) or 5alpha-reductase inhibitors. The long-term effect of these drugs, singly or combined, on the risk of clinical progression is unknown.


METHODS
We conducted a long-term, double-blind trial (mean follow-up, 4.5 years) involving 3047 men to compare the effects of placebo, doxazosin, finasteride, and combination therapy on measures of the clinical progression of benign prostatic hyperplasia.


RESULTS
The risk of overall clinical progression--defined as an increase above base line of at least 4 points in the American Urological Association symptom score, acute urinary retention, urinary incontinence, renal insufficiency, or recurrent urinary tract infection--was significantly reduced by doxazosin (39 percent risk reduction, P<0.001) and finasteride (34 percent risk reduction, P=0.002), as compared with placebo. The reduction in risk associated with combination therapy (66 percent for the comparison with placebo, P<0.001) was significantly greater than that associated with doxazosin (P<0.001) or finasteride (P<0.001) alone. The risks of acute urinary retention and the need for invasive therapy were significantly reduced by combination therapy (P<0.001) and finasteride (P<0.001) but not by doxazosin. Doxazosin (P<0.001), finasteride (P=0.001), and combination therapy (P<0.001) each resulted in significant improvement in symptom scores, with combination therapy being superior to both doxazosin (P=0.006) and finasteride (P<0.001) alone.


CONCLUSIONS
Long-term combination therapy with doxazosin and finasteride was safe and reduced the risk of overall clinical progression of benign prostatic hyperplasia significantly more than did treatment with either drug alone. Combination therapy and finasteride alone reduced the long-term risk of acute urinary retention and the need for invasive therapy.
McConnell
John D
JD
University of Texas Southwestern Medical Center, Dallas, TX 75390-9110, USA.
Roehrborn
Claus G
CG
Bautista
Oliver M
OM
Andriole
Gerald L
GL
Dixon
Christopher M
CM
Kusek
John W
JW
Lepor
Herbert
H
McVary
Kevin T
KT
Nyberg
Leroy M
LM
Clarke
Harry S
HS
Crawford
E David
ED
Diokno
Ananias
A
Foley
John P
JP
Foster
Harris E
HE
Jacobs
Stephen C
SC
Kaplan
Steven A
SA
Kreder
Karl J
KJ
Lieber
Michael M
MM
Lucia
M Scott
MS
Miller
Gary J
GJ
Menon
Mani
M
Milam
Douglas F
DF
Ramsdell
Joe W
JW
Schenkman
Noah S
NS
Slawin
Kevin M
KM
Smith
Joseph A
JA
D058891:5-alpha Reductase Inhibitors; D000317:Adrenergic alpha-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000704:Analysis of Variance; D018450:Disease Progression; D004311:Double-Blind Method; D017292:Doxazosin / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018120:Finasteride / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011470:Prostatic Hyperplasia / Q000145:classification / Q000188:drug therapy* / Q000601:surgery; D012720:Severity of Illness Index
D058891:5-alpha Reductase Inhibitors; D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D018120:Finasteride; D017292:Doxazosin