Two drugs commonly used to treat benign prostatic hyperplasia (BPH)
<www.niddk.nih.gov/health/urolog/pubs/prostate/index.htm> are more
effective in combination than alone to prevent progression of this
condition, according to results of a multi-center National Institutes of
Health clinical trial being presented at the American Urological Association
(AUA) meeting in Orlando on May 28.

The Medical Therapy of Prostatic Symptoms (MTOPS) Trial found that compared
to placebo the 5 alpha-reductase inhibitor finasteride (Proscar) and alpha-1
receptor blocker doxazosin (Cardura) together reduced the risk of BPH
progression by 67 percent. The risk of progression was reduced by 39
percent with doxazosin alone and by 34 percent with finasteride alone.

An estimated 9 million men suffer from BPH symptoms, and about 400,000 have
surgery each year to remove some of the enlarged gland, which impairs the
flow of urine through the urethra. Symptoms include urinary urgency,
frequency, and nighttime urination.

"This is the kind of clear-cut result we all strive for when we launch a
clinical trial," says Leroy M. Nyberg Jr., Ph.D., M.D., whose urology
research program at the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) funded the study. "The evidence supporting
combination therapy in selected patients is so strong that I expect to see
major changes in medical practice in the near future."

Physicians at 17 medical centers
<www.niddk.nih.gov/welcome/releases/05-28-02centers.pdf>treated
about 3,000 men age 50 and up for an average of 4.5 years. The men all had
BPH and were evenly divided into four groups that took either 5 mg
finasteride, 4 mg or 8 mg doxazosin, both drugs, or a placebo. The aim of
the trial was to prevent BPH progression, defined primarily as either a
significant worsening of symptoms, recurring urinary tract infection,
urinary retention, incontinence or invasive therapy such as surgery.

Compared to placebo, the risk of urinary retention was reduced by 79 percent
with combination therapy, by 67 percent with finasteride and by 31 percent
with doxazosin (not significantly different from placebo), and the risk of
invasive therapy was reduced by 69 percent with the combination, by 64
percent with finasteride and by 8 percent with doxazosin (not significantly
different from placebo).

"Combination therapy not only provides better long-lasting symptom relief,
but because finasteride reduces prostate size, patients have fewer episodes
of urinary retention and invasive treatments," says MTOPS trial leader John
McConnell, M.D., professor of urology and executive vice president of the
University of Texas Southwestern Medical Center in Dallas. "In addition,
the study clearly demonstrates which patients are at increased risk of
progression and most likely to benefit from treatment, which we will discuss
at the AUA meeting."

When MTOPS began, doctors were prescribing each drug individually for BPH
symptoms. But some doctors were concerned that while single-drug therapy
provided partial relief, symptoms might worsen over time or the prostate
might continue to enlarge, blocking the flow of urine and damaging the
bladder and kidneys.

"In MTOPS, the rates of urinary tract infection and urinary incontinence
were low in all drug treatment groups, and no patient in any group developed
kidney problems from BPH. So we are very pleased," says Nyberg.

Investigators plan to publish study data later this year. The abstract for
Dr. McConnell's AUA presentation is available at
<www.niddk.nih.gov/welcome/releases/05-28-02abstract.pdf>.

STUDY SPONSORS: The National Institute of Diabetes and Digestive and Kidney
Diseases and National Center on Minority Health and Health Disparities
funded the study, and Pfizer Inc., New York City; and Merck & Co., Rahway,
New Jersey, donated products.