A one-two punch for combating BPH

The latest word on treatment is that combined
alpha-blockers and dual 5-alpha-reductase
inhibitors is better that either drug alone

By Mairi McKinnon

An aging man's odds of developing benign prostatic hyperplasia (BPH) are better than good: half of all men show evidence of the condition at age 60, and after age 85 prevalence rockets to over 80%. An overgrown prostate can cause serious problems if left untreated, including acute urinary retention, incontinence, infection and permanent bladder, kidney and urethral damage. Research efforts have recently been stepped up to look for safe non-surgical options.

Evidence is settling on long-term combined therapy for BPH, using alpha-blockers plus a dual 5-alpha-reductase inhibitor (5 A-RI). The latest comes from the Medical Therapy of Prostatic Symptoms (MTOPS) study, in December in the New England Journal of Medicine. MTOPS found that after an average of 4.5 years, combined finasteride (Proscar) and alpha-blockade using doxazosin (Cardura) was far more effective than either one used alone, or a placebo, in improving urinary-renal symptoms and risk of disease progression in a study of more than 3,000 men. But the study's authors also concluded that while finasteride by itself lowered the long-term risk of acute urinary retention and surgical intervention, there was no such association with the alpha-blocker.

By themselves, alpha-blockers are the most commonly prescribed drug for the urinary retention symptoms of BPH, but not much is known about their immediate effects. How effective are they? The November issue of Urology published the answer: a U.S. randomized, placebo-controlled trial headed by Dr Leonard S. Mark reported that 10 mg of alfuzosin (Uroxatral) OD significantly increased peak urinary flow as soon as eight hours after the initial dose (3.2 mL/s, compared to 1.1 mL/s for placebo). No serious adverse events were reported (three patients treated with alfuzosin experienced dizziness, compared to only one on placebo).

More research is now getting underway. A promising multicentre trial -- combination of Avodart [dutasteride] and tamsulosin (COMBAT) -- is evaluating the efficacy and safety of dutasteride 0.5 mg, a 5 A-RI, alone and in combination with alpha-blockade using tamsulosin (Flomax) 0.4 mg OD. Funded by GlaxoSmithKline, it will run for four years and enroll 4,500 men over age 50 with confirmed BPH, have PSA levels between 1.5-10 ng/mL, a prostate volume of 30 cc or greater and moderate to severe urinary symptoms. Candidates cannot have had previous prostate surgery or a history of prostate cancer or chronic prostatitis. This study differs from MTOPS in one key respect: according to trial investigator Dr. Claus Roehrborn from the University of Texas Southwestern Medical Center in Dallas, "the dutasteride and tamsulosin study will shed new light on the long-term effects of combination therapy for a particular group of patients -- those at higher risk for disease progression."