Anti-inflammatory Drugs, the Prostate, and the Bladder

For young men, a full bladder is no big deal; a quick trip to the bathroom is all it takes to return to empty. But for many older gents, it's an altogether different matter. In most cases, the issue is benign prostatic hyperplasia (BPH), an enlargement of the gland that pinches the urethra, slowing the flow of urine and often causing bothersome symptoms such as an urgent need to void, frequent urination, incomplete emptying of the bladder, dribbling, and nighttime urination.

The treatment of BPH has come a long way, thanks to major advances in medical and minimally invasive surgical therapies. There is also hope that experimental new treatments such as Botox injections will soon become available. But despite all these options, every man with BPH should avoid anything that might make the situation worse.

Medications are high on the list of potential culprits. The most common offenders are over-the-counter remedies for colds and allergies. Decongestants such as pseudoephedrine tighten the sphincter muscles at the base of the bladder, and antihistamines such as chlorpheniramine weaken the contractions of the bladder muscle. In some cases, these simple medications may make it impossible for a man to void. Doctors call it acute urinary retention. The bladder fills to capacity, often holding more than a quart of urine. A small amount of urine may force its way out, but the trickle is not enough to relieve the pressure, which is very painful.

Acute urinary retention is a urological emergency, requiring prompt placement of a Foley catheter to drain the bladder. Next comes aggressive treatment of BPH so the catheter can be removed. Most men return to unassisted urination, but all men who face the threat of acute urinary retention should do everything possible to prevent the problem.

A study from the Netherlands raises the possibility that another commonly used group of medications may belong on the worry list, but an American study offers a different perspective.

The Dutch Treatment Study

Dutch researchers have been maintaining a database of information from the electronic medical records of about 500,000 patients. The information is quite complete, including age, gender, symptoms, diagnoses, medications, and hospital treatments.

Focusing on men 45 years of age and older, researchers identified 536 cases of acute urinary retention. For comparison, the scientists also investigated 5,348 men who were matched to the cases for age and the amount of time they had been under scrutiny.

The risk of acute urinary retention was twice as high in men taking nonsteroidal anti-inflammatory drugs (NSAIDs) as in men who were not using them. The likelihood of acute urinary retention was greatest in men who had recently started taking an NSAID and in those using high doses of the medication; their risk was 3.3 times higher than that of men who were not taking NSAIDs.

NSAIDs are common medications that are used for many medical problems. To see if urinary retention was linked to an NSAID or to underlying conditions, the scientists checked a long list of problems, including medications that affect the bladder and prostate, urinary tract infection and inflammation, kidney stones, surgery and immobility, neurological disorders, BPH, and prostate cancer. Even after considering all these factors, the link between NSAIDs and acute urinary retention held up.

The Men of Minnesota

To evaluate the long-term effects of NSAIDs on the prostate, scientists in Minnesota evaluated 2,447 men between 1990 and 2002. None of the volunteers had a history of urological disease. Every two years, the men provided detailed information about NSAID use and BPH symptoms; at the same time, each man's peak urinary flow rate was measured at home. A randomly selected group of 634 men also underwent PSA measurement and transrectal ultrasound (TRUS) exams to measure prostate size.

When the results were tallied, daily NSAID use was linked to a reduced risk of developing BPH symptoms and slow urinary flow rates. Men taking NSAIDs daily also appeared to have smaller prostate glands and lower PSA levels.

Reconciling the Studies

At first glance, the Dutch and American studies appear contradictory. But a closer look suggests that NSAIDs may be both friend and foe, depending on the stage of BPH and the part of the urinary tract that's vulnerable.

The American study recruited men without urologic disease and evaluated the onset of BPH symptoms. There is emerging, though still incomplete, evidence that inflammation may play a role in the development of BPH. If that's the case, regular NSAID use might slow the process and delay the onset of symptoms.

In contrast, the Dutch study excluded only men who had had radical cystectomies or previous episodes of urinary retention. Instead of evaluating the onset of symptoms, the scientists evaluated late-symptom, acute urinary retention. And they found that men who had recently begun taking NSAIDs were at the highest risk of urinary retention. As a result, the men with acute retention may have been developing BPH for years before they started taking NSAIDs — and the NSAIDs may have caused trouble by acting on the bladder, not the prostate.

Why NSAIDs?

It's a new idea, but it fits with what doctors know about bladder function. The bladder tissue produces chemicals called prostaglandins, which enhance the contractions of the detrusor muscle that empties the bladder. NSAIDs treat pain and inflammation by inhibiting prostaglandin production. But as an unintended consequence, NSAIDs may also make it harder for the bladder to empty, especially when it's already challenged by BPH.

What to Do

The table above lists NSAIDS and closely related medications that both reduce inflammation and cut prostaglandin production.

It's a long list that includes many important medications. Should younger men consider them to prevent BPH, and should older men with BPH shun them altogether?

No and no. For one thing, these studies are the first of their kind, and they need to be confirmed. In addition, the Dutch study exonerated low-dose aspirin, so men taking aspirin for cardiac protection need not be concerned. And all men would be wise to use NSAIDs judiciously, taking the lowest effective dose for the shortest duration necessary. It's good advice for women and younger men, too, since these precautions can reduce the risk of other NSAID complications, such as gastric irritation and bleeding, elevated blood pressure, kidney dysfunction, fluid retention, and cardiovascular events.

In both the Netherlands and the United States, men with BPH should think before they flush. If they note an increase in BPH symptoms while taking an NSAID, they should inform their doctors and reduce or avoid NSAIDs, possibly by substituting a pain reliever such as acetaminophen (Tylenol and other brands), which does not affect prostaglandins in the bladder.

When you've got to go, you want to be able to go.