The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia

N Engl J Med. 2003 Dec 18;349(25):2387-98. doi: 10.1056/NEJMoa030656.

Abstract

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5-alpha Reductase Inhibitors*
  • Adrenergic alpha-Antagonists / adverse effects
  • Adrenergic alpha-Antagonists / therapeutic use*
  • Analysis of Variance
  • Disease Progression
  • Double-Blind Method
  • Doxazosin / adverse effects
  • Doxazosin / therapeutic use*
  • Drug Therapy, Combination
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Finasteride / adverse effects
  • Finasteride / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Prostatic Hyperplasia / classification
  • Prostatic Hyperplasia / drug therapy*
  • Prostatic Hyperplasia / surgery
  • Severity of Illness Index

Substances

  • 5-alpha Reductase Inhibitors
  • Adrenergic alpha-Antagonists
  • Enzyme Inhibitors
  • Finasteride
  • Doxazosin