As a man matures, his prostate gland goes through two main periods of growth. The first occurs early in puberty, when the prostate doubles in size. At around age 25, the gland begins to grow again. It is this second growth phase that often results, years later, in benign prostatic hyperplasia (BPH) . Fortunately, BPH rarely causes symptoms before the age of 40, but more than 50% of men in their 60s and 90% of men in their 70s and 80s have some symptoms of BPH.

The prostate gland is a walnut-sized gland located at the neck of the bladder where it surrounds the urethra. It is enclosed in a layer of tissue called the prostatic capsule. As the prostate continues to grow, the prostatic capsule stops it from expanding, causing the gland to squeeze the urethra like a clamp on a garden hose. This can cause the bladder wall to thicken and become irritable. When this happens, the bladder may begin to contract even when it contains only small amounts of urine, causing more frequent urination. In some cases, the bladder may even lose the ability to empty itself, causing urine to remain in the bladder. This sets the stage for the symptoms of BPH, which include:

  • Difficulty urinating
  • Weak stream
  • Dribbling at end of urination
  • Sensation of incomplete bladder emptying
  • Urge to urinate frequently, especially at night
  • Deep discomfort in lower abdomen

In more severe cases, BPH can lead to acute urinary retention (the loss of the bladder’s ability to empty itself), urinary incontinence , or recurrent urinary tract infections (UTIs) .

Treatment of BPH usually involves a trial of medications before surgery is considered. Traditionally, most men are prescribed either an alpha-blocker (to reduce muscle spasms in the bladder and relax the urethra) or a 5 alpha-reductase inhibitor (to reduce the size of the prostate itself). Now, a new study, published in the December 18, 2003 issue of the New England Journal of Medicine, suggests that combining these two drugs is both safe and effective in reducing the clinical progression of BPH.

About the study

The researchers enrolled 3047 men, all of whom were age 50 or older and had symptoms of BPH that ranged from nonexistent to severe. Each participant was randomly assigned to one of four treatment groups:

  • Placebo
  • Doxazosin (Cardura) 4-8 mg (the alpha-blocker)
  • Finasteride (Propecia) 5 mg (the 5 alpha-reductase inhibitor)
  • Combination therapy with doxazosin and finasteride

Every three months, the researchers assessed the participants’ vital signs, urologic symptoms, urinary flow rate, compliance with treatment, and any adverse events they may have been experiencing. The participants also underwent digital rectal exams (DREs), prostate specific antigen tests (PSA; to screen for prostate cancer), and urinalysis annually. Their primary objective was to compare the effects of placebo, doxazosin, finasteride, and combination therapy measures on the overall clinical progression of BPH.

The findings

The researchers followed the men in the study for an average of 4.5 years. They found that the risk of overall clinical progression of BPH (the development of acute urinary retention, urinary incontinence, and renal insufficiency ) was reduced by 39% by doxazosin, 34% by finasteride, and 66% by combination therapy with both drugs. The rate of overall clinical progression was 10% in both the doxazosin and finasteride groups and 5% in the combination therapy group.

The most common adverse events seen in the combination therapy group were the same as those for the individual drugs except that certain adverse events (abnormal ejaculation, peripheral edema (swelling), and difficulty breathing occurred more frequently in those taking both drugs.

How does this affect you?

The researchers concluded that long-term combination therapy with doxazosin and finasteride is safe and reduced the risk of overall clinical progression of BPH significantly more than treatment with either drug alone. They also found that combination therapy and finasteride alone reduced the long-term risk of the more severe symptoms of BPH including acute urinary retention and the need for invasive therapy.

These findings are no doubt welcome news for the many men who suffer from BPH, particularly those who feel the quality of their lives or their ability to take care of themselves have been adversely affected. Hopefully, the widespread adoption of this combination therapy will reduce the number of surgeries and ongoing medical difficulties for men at particularly high risk for these complications.