Growing older has its perks -- heftier income, respect of one's peers -- and its drawbacks such as, for men, a steady enlargement of the prostate gland.
Soon, men with this problem may have a broader set of therapeutic options.
A 2003 study already has revolutionized the standard of care men get for this common condition. And new ideas about treating the symptoms of prostate gland enlargement now have doctors treating men with drugs better known for their effects on erectile dysfunction and wrinkled skin.
Viagra and Botox are just two of several drugs being studied for treating problems with urination and benign prostatic hyperplasia, the term for overgrown but noncancerous prostates that occur in most men as they age.
The oft-reported numbers are startling: At least 2 of 3 sixtysomething men have symptoms of an enlarged prostate gland, the organ that produces semen. Symptoms can be merely bothersome -- the need to urinate often, poor urine flow and incomplete emptying of the bladder. Or they can be serious enough to require treatment: bladder and kidney dysfunction; stones or infection in the bladder; and urinary retention -- inability to urinate at all.
Drug use is fairly recent
Using drugs to treat enlarged prostates is fairly new. "Twenty years ago, we never used medications," says Dr. Steven Kaplan, a urologist at Weill Cornell Medical College in New York. Instead, when the condition became advanced, surgeons would cut away excess tissue.
Then a five-year study of 3,047 men published in the New England Journal of Medicine in 2003 caused a shift in medical practice. It found that a combination of two drugs helped relieve symptoms and halted the progression of the condition. "Now medications are the standard of care," says Kaplan, a coauthor of that research. Surgery is now reserved for men with very large prostates or intractable symptoms.
One of the drugs tested in that study is doxazosin (Cardura), which relaxes muscle in the prostate and bladder. This helps men maintain a steady urine stream and empty their bladders more completely.
The other drug, finasteride (Proscar), blocks the synthesis of a hormone thought to spur prostate growth and can reduce prostate size.
Study coauthor Dr. Claus Roehrborn, a urologist at the University of Texas Southwestern Medical Center in Dallas, says that interim results from a second long-term study of 4,800 men have corroborated the superiority of combination therapy, although with different drugs -- the alpha blocker dutasteride (Avodart), a drug in the same class as doxazosin, and tamsulosin (Flomax), which, like finasteride, is in a class of drugs called 5-alpha-reductase inhibitors.
Doctors agree that alpha blockers are primarily responsible for ameliorating symptoms. But preventing the big risks, urinary retention and surgery, requires the combination.
And new approaches are under study. "What used to be a two-horse race has just exploded," Kaplan says.
Prostate health is by definition a man's issue. Yet one of the most promising new treatment drugs is borrowed from women's troubles with urinary urgency, termed "overactive bladder" by doctors. Doctors avoided the drugs in the past, fearing that supressing bladder activity would increase the risk of urinary retention in men. That fear has not been borne out in several studies, including a 2006 trial of more than 800 men published in the Journal of the American Medical Assn. In it, tolterodine (Detrol LA), used to treat urinary incontinence, decreased urinary symptoms associated with an enlarged prostate. Side effects were minimal, and rates of urinary retention were low and unaffected by drug treatment.
No study has shown that drugs for overactive bladder are better than combination therapy, but they may be helpful in men whose symptoms are due to a bladder issue rather than the effect of the prostate leaning on the bladder, researchers say.
Another new drug development comes from anecdotal reports that men taking drugs for erectile dysfunction were urinating better. In response, drug companies, including Pfizer (which markets Viagra) and GlaxoSmithKline (which markets Levitra) and Eli Lilly & Co. (which markets Cialis) are studying their erectile dysfunction drugs in men with benign prostatic hyperplasia.
One of these studies, of vardenafil (GlaxoSmithKline's Levitra), was published earlier this year in European Urology. In it, 222 German men were given either vardenafil or a placebo for eight weeks. Those receiving the drug reported improved urination equivalent to that obtained with Flomax, as well as improved erectile function and quality of life.
And Roehrborn this month will present results from an Eli Lilly-funded clinical trial at an American Urologist Assn. meeting showing that tadalafil (Cialis) was as effective or better than the alpha blocker drugs in improving enlarged prostate symptoms.
Roehrborn says prescribing these drugs for benign prostatic hyperplasia may help remove the stigma of erectile dysfunction. "Think about the psychology. Men take it for a medical condition, a legitimate reason. But because they take it daily, their sexual function is adequate 24/7."
Another development in the works: Botulinum toxin (Botox), which causes muscle paralysis and is used cosmetically to treat wrinkles. A small 2006 study of 41 men, published in the journal BJU International, found improvement in lower urinary tract symptoms and quality of life when Botox was injected into the prostate. Prostate size decreased by an average of 15%, but even in subjects whose prostates did not shrink, urinary function was normalized. Additional Botox studies are underway, including one sponsored by the National Institutes of Health and led by Dr. Kevin McVary, a urologist at Northwestern University Feinberg School of Medicine in Chicago.
For now, McVary says, standard treatment means that a patient with many symptoms who desires treatment should be offered an alpha blocker. If the gland is large, he should also be offered a 5-alpha-reductase inhibitor to avoid long-term consequences. Developing an enlarged prostate is the first time many men confront the likelihood of taking drugs every day for the rest of their lives. "People still have this notion that they can 'make the disease go away,' " Roehrborn says. They cannot, he adds. "You stop the medication, the prostate actually physically grows back," he says.
But future medications will be applied with more precision, Kaplan predicts. "You have to tailor the therapy to the size of the prostate, as well as the type of symptoms," he says. "Some prostates do better by shrinking them; some prostates do better by relaxing the muscle. . . . I think the challenge is to figure out which drugs work for which patients."
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Age, genetics and hormones are the usual causal suspects in benign prostatic hyperplasia, but now some data suggest that the condition is a consequence of our Western lifestyle. In a 2006 study of 422 men published in the Journal of Clinical Endocrinology and Metabolism, Dr. J. Kellogg Parsons, a urologist at UC San Diego, found that men who were obese had an increased risk of prostate enlargement, with severely obese men at 3.5 times higher risk.
In another paper published this year in European Urology, Parsons pooled data from 11 studies involving about 43,000 men and found that those who engaged in regular physical activity had about a 25% lowered risk of enlarged prostates.
It's emerging evidence, Parsons says, "that the same risk factors that are contributing to cardiovascular disease, obesity and diabetes likely are contributing in some way to [benign prostatic hyperplasia]."
For now, the evidence is based on studies comparing lifestyles of men who do or don't develop enlarged prostates. More convicing, but not yet done, would be studies in which groups of men are put on diet and exercise regimens and then tracked to see whether rates of enlarged prostates differ. Still, Parsons counsels his patients on lifestyle factors for prostate health. "We don't have definitive data, but there's very little downside," he says.
Jill U. Adams
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Saw palmetto findings are conflicting
Extract of saw palmetto, the Serenoa repens plant, has long been promoted as a way to prevent the prostate from growing large.
"There are studies that show it works and there are studies that show it doesn't work. And if you look at it very, very closely, the studies where it doesn't work are the good studies -- randomized, multi-center, controlled studies," says Dr. Claus Roehrborn, a urologist at the University of Texas Southwestern Medical Center in Dallas. "My take on it is, it ain't working."
A 2002 review of saw palmetto studies published in the Cochrane Database of Systematic Reviews found moderate effects of saw palmetto on symptoms and urine-flow measures. Yet the review was critical of the methodologies used in the studies: Of the 21 included in the review, only 13 compared the effects of saw palmetto with a placebo group, and only one used a symptom scale in line with internationally accepted standards. Studies were generally done on a small number of subjects and lasted 13 weeks on average.
A large study published in the New England Journal of Medicine in 2006 gave 225 men either saw palmetto or a placebo for a year and found no effect on self-reports of urinary symptoms or quality of life or on objective measures such as prostate size or urine-flow rate.
It's possible that higher doses of the extract may provide better or more consistent results, says Dr. Kevin McVary, a urologist at Northwestern University Feinberg School of Medicine in Chicago. McVary is working on a National Institutes of Health-funded study to address that unknown.
-- Jill U. Adams