Combination therapy significantly delays progression of benign prostatic hyperplasia

December 17, 2003

A five-year, multicenter study, published today in The New England Journal of Medicine, provides the first scientific evidence that combining alpha-blocking doxazosin with the drug finasteride is significantly more effective than using either treatment alone, said Dr. John McConnell, UT Southwestern's executive vice president for health system affairs and lead author of the study. The clinical trial involved more than 3,000 men and 20 major medical centers across the United States and is the largest study of its kind ever conducted.

Use of finasteride alone or the combination therapy significantly reduced the risk of acute urinary retention and the need for surgical intervention. A surprising finding of the study was that the alpha blocker doxazosin was not effective in reducing the long term risk of acute urinary retention or need for surgical therapy.

"Although we had predicted that combination therapy would be more effective than either drug alone, the magnitude of risk reduction was surprising," said Dr. McConnell, the former UT Southwestern chairman of urology who is internationally known for leading the development of clinical practice guidelines for the treatment of BPH in 1994. Dr. McConnell also directs the National Institutes of Health's George M. O'Brien Urologic Research Center at UT Southwestern.

These findings culminate three decades of research at UT Southwestern that began with Dr. Jean Wilson's discovery of the role of the enzyme 5-alpha reductase in benign growth of the prostate. The enzyme would later be the target for the drugs finasteride and dutasteride. The class of drugs inhibit the 5-alpha reductase enzyme, significantly lowering the level of the primary male hormone in the prostate, dihydrotestosterone, without affecting the level of testosterone elsewhere in the body.

"Dr. Wilson's discovery set in motion a whole new era of treatment," Dr. McConnell said. "What we have shown in this trial is that while the alpha blocker (doxazosin) clearly contributes to symptom relief and a reduction in symptom worsening, use of finasteride to shrink the prostate and prevent further prostate growth is required to reduce the long-term complications of the disease, like the development of urinary retention or the need for invasive therapy."

The double-blind study followed 3,047 men with BPH over a four-and-a-half-year period. Study subjects were randomly given either doxazosin, finasteride, the combination therapy or a placebo. The combination of the two drugs "significantly delayed the clinical progression of BPH as compared with each drug individually among men with symptomatic BPH," the study concluded. In general, both drugs were well-tolerated by patients. Sexual function side effects occur in approximately 10 percent of men taking finasteride. Dizziness, low blood pressure, and fatigue can occur with alpha blockers like doxazosin.

"A 66 percent reduction in the risk of anything in medicine is pretty substantial," said Dr. Claus Roehrborn, UT Southwestern's chairman of urology and a trial investigator. "This is good news. The fly in the ointment is that two tablets cost more than one, so there is a cost factor."

In June, another study published in The New England Journal of Medicine demonstrated that the drug finasteride reduces the risk of prostate cancer by 25 percent.

BPH is a noncancerous enlargement of the prostate affecting more than half of all men over 60 in the United States. Symptoms can include frequent or urgent need to urinate, slowing of the urinary stream and hesitancy in urinating. With disease progression, some men can develop recurrent urinary tract infection and acute urinary retention. Surgery is still standard therapy for men who have developed complications of BPH.
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The study was funded by the National Institute of Diabetes, Digestive and Kidney Diseases. Other participating medical centers included Yale University School of Medicine, the Mayo Medical School and Northwestern University Feinberg School of Medicine.

UT Southwestern Medical Center

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