Drug Combination for Benign Enlarged Prostate Clearly Superior to Reduce Symptoms, Keep Men From Catheterization and the OR

Monday, December 15, 2003

ROCHESTER, Minn. — A combination drug treatment for men with noncancerous enlarged prostate can significantly abate urination issues and help avoid surgery or catheterization for at least five years in the majority of sufferers, according to a national, multicenter study in which Mayo Clinic participated.

This study included 3,047 men at 17 medical centers who were randomized in a double-blind trial to placebo, doxazosin, finasteride or combination therapy with doxazosin plus finasteride, and then followed for five years. The study found the combination treatment reduced the risk of the condition worsening to the point where invasive therapy was needed by two-thirds compared to placebo and also reduced urination symptoms far more effectively than the single drug treatments or placebo. The study results will be published in the Thursday, Dec. 18 issue of New England Journal of Medicine, http://content.nejm.org/.

"The results are very good news because they show that combination treatment for benign prostate enlargement with two different drugs is twice as effective as single drugs alone," says Michael Lieber, M.D., Mayo Clinic urologist and principal investigator at the Mayo Clinic study site. "For men who have lower urinary tract symptoms, the combination of the two drugs together gives the most reduction of the symptoms and also keeps them from getting worse so men can avoid having to have prostate surgery or a catheter.

"We've known for a long time that the two drugs improved symptoms. What's new with this study is that it went five years into the future and showed that the things men are trying to avoid — they don't want to have prostate surgery, they don't want to be catheterized and they don't want their symptoms to progress — are prevented by the drugs, which stop progression of the condition."

This condition, formally called benign prostatic hyperplasia, affects one-half of men over age 60 and approximately 80 percent of men age 80 and older. Starting around the age of 40, it is normal for a man's prostate gland to enlarge. This growth can cause problems, however, if it starts to block the urethra and impede urine flow. Previously, urination issues due to enlarged prostate have been treated with two kinds of medications: alpha-adrenergic-receptor antagonists — also called alpha-blockers, — however, is whether these medications, used together or singly, not only alleviate symptoms but prevent them from worsening and requiring a much more invasive fix for the condition.

The researchers found that the risk of clinical progression, or worsening of the disease, was reduced 39 percent by the drug doxazosin and 34 percent reduced by the drug finasteride, compared with a placebo. Combining the two drugs, however, proved to have a much more significant effect: it reduced the risk of the condition worsening by 66 percent compared with a placebo. Worsening of the condition includes acute urinary retention, urinary incontinence, renal insufficiency or recurrent urinary tract infection.

Men with benign prostate enlargement experience symptoms such as frequent need to urinate, urgency to urinate, having to urinate again immediately after urination and poor bladder emptying.

"One of the typical things that we see in urology is as men get older — in their 60s and 70s — they start getting up at night to urinate, perhaps three, four or five times," explains Dr. Lieber. "When they get up, they have trouble falling back to sleep. They also disturb the sleep of their wives, and that often gets them in to see the urologist. It does impede lifestyle during the daytime, too, because the men often have urination frequency and urgency issues. So, all of the time they're thinking about where the bathroom is so they can get there quickly."

When quality of life starts to erode significantly, men tend to seek medical attention, according to Dr. Lieber. "What prompts most of the men to come in to see a physician is that their symptoms get severe enough that it's upsetting their lives, such as being afraid that they can't get to the toilet in time and that they're going to wet their clothing."

Doxazosin or finasteride alone also reduced men's symptoms of enlarged prostate. A combination of the two drugs had an even more powerful effect on symptom reduction. Major symptoms addressed include urinary flow rate, serum PSA levels and prostate volume.

After four years of treatment, urinary flow compared with patients given placebo was improved by 4.0 milliliters per second for patients given doxazosin alone, 3.2 milliliters per second for patients given finasteride alone, and 5.1 milliliters per second for patients given the two drugs combined. Serum PSA levels at the four-year mark were reduced by 50 percent in patients given finasteride alone or the combination therapy, compared with an increase in PSA level of 15 percent in those given placebo alone and 13 percent in those given doxazosin alone. Finally, at an average follow-up time of 4.5 years, men who had large prostate volumes at the start of treatment who received finasteride alone or the two-drug combination had a median decrease in prostate volume of 19 percent; the volume increased by a median of 24 percent in those given placebo or doxazosin alone.

Some side effects are associated with the two drugs, but they only trouble about 5 to 10 percent of men prescribed them, says Dr. Lieber. Side effects of doxazosin include dizziness, weakness or nasal stuffiness; finasteride can cause decrease in sexual interest or trouble with erections.

Duration of the combination treatment's effectiveness in reducing symptoms and need for more invasive treatment beyond five years is unknown, but Dr. Lieber is hopeful the relief would last double that time. "The study only went for five years, but for the men who were getting combination treatment, even at five years the rate of their progressing and needing surgery was so low, that we're optimistic it could be extended for another five years."

Men appropriate for the combination or single-drug treatments for benign prostate enlargement have moderate to severe urination symptoms and are unhappy with their quality of life. Men who have larger prostates are better treated by these medicines than men who have smaller prostates, Dr. Lieber indicates.

Dr. Lieber encourages men not to put off talking to their physicians about urination symptoms, as the treatment is unlikely to be invasive. "A man should see his primary care doctor or his urologist when his symptoms are troublesome enough, because we have medical therapy. Most men are happy to take pills, but they really don't want to have surgery if they can avoid it. So, it's important for men to know that single drugs or a combination of drugs are available that can help."

For more information about noncancerous enlarged prostate, see www.mayoclinic.com. For information on future enlarged prostate research studies, call the Mayo Clinic Urology Research Unit at 507-284-3369.

Lisa Copeland
507-284-5005 (days)
507-284-2511 (evenings)
e-mail: newsbureau@mayo.edu

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