天博体育

Michael P. O鈥橪eary, M.D., M.P.H., looks at what may be ahead

Prostatitis gets little press, but it鈥檚 an all-too-common genitourinary condition in men. It accounts for about 1.8 million visits to the doctor鈥檚 office in the United States each year. Depending on how you define the term, 9% to 16% of men experience prostatitis. It鈥檚 also an 鈥渆qual opportunity鈥� disorder. Unlike benign prostatic hyperplasia (BPH) and prostate cancer, which predominantly affect older men, prostatitis affects men of all ages.

Despite its commonness, little is known about what sparks prostatitis or, more importantly, how to treat it. Frustrated patients visit one doctor after another in search of a remedy, but they usually leave disappointed. Relative to other prostate conditions, little research has been conducted on prostatitis. But a few bright spots may be emerging.

What is prostatitis?

The term prostatitis, which translates to inflammation of the prostate, refers to a loose assemblage of syndromes characterized by urinary problems 鈥� for example, burning or painful urination, urgency, and trouble voiding 鈥� difficult or painful ejaculation, and pain in the perineum or lower back. The National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health, classifies prostatitis into four categories, each with its own treatment approach (see Table 1).

Category I and Category II refer to acute and chronic bacterial prostatitis, respectively. They are both associated with an infection of the prostate. Acute prostatitis begins abruptly with high fever, chills, joint and muscle aches, and profound fatigue. In addition, you may have pain around the base of the penis and behind the scrotum, pain in the lower back, and the feeling of a full rectum. As the prostate swells, you may find it more difficult to urinate. Unlike the acute form, chronic bacterial prostatitis is a subtle, low-grade infection that can begin insidiously and persist for weeks or even months. Together, these conditions, which can be treated with antibiotics, account for about 5% to 10% of prostatitis cases.

Category III prostatitis, also known as chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), accounts for almost all other cases of prostatitis. (Category IV is rare; it has no symptoms and usually requires no treatment.) It鈥檚 characterized by episodes of pain and discomfort that come and go unpredictably, as well as the urinary difficulties and sexual dysfunction mentioned above. Quality of life takes a beating, too. The pain can be disabling, causing a man to withdraw from activities and become depressed.

A major difficulty is that in most cases doctors are unable to definitively diagnose CP/CPPS or identify a causative agent. Not surprisingly, with so little to go on, treatment is empiric 鈥� guided by a doctor鈥檚 clinical experience and instincts rather than hard evidence of what actually works, which isn鈥檛 much. Patients often find that the 鈥渟tandard鈥� treatments provide little or only temporary relief.

The 鈥渢hree A鈥檚鈥�

Known as the 鈥渢hree A鈥檚,鈥� traditional treatments for chronic nonbacterial prostatitis/chronic pelvic pain syndrome are antibiotics, anti-inflammatory medications, and alpha blockers.

The use of antibiotics remains controversial. For starters, few men with CP/CPPS test positive for bacterial infection. This suggests that antibiotics aren鈥檛 likely to be helpful, and randomized clinical trials bear this out. (See 鈥淚neffectiveness of antibiotics.鈥�) Even so, many doctors still prescribe a single course of antibiotics lasting several weeks, arguing that a negative test for bacteria doesn鈥檛 mean that bacteria aren鈥檛 present. Also, some antibiotics have anti-inflammatory properties, but work differently from other anti-inflammatory medications. This means they may help some men even when symptoms aren鈥檛 caused by a bacterial infection.

Repeat courses of antibiotics probably aren鈥檛 helpful. Even though they generally have few side effects, they aren鈥檛 without risk. They can cause nausea, vomiting, and diarrhea; interfere with other medications; and trigger allergies.

Anti-inflammatory medications, notably aspirin or NSAIDs such as ibuprofen, help some men cope with the pain of CP/CPPS. Yet only one controlled study supports the use of NSAIDs as the primary treatment for CP/CPPS. Most doctors agree that if NSAIDs are used, they should be taken for a limited period of time, to control pain, and preferably with another medication, such as an alpha blocker.

Alpha blockers (see Table 2) are most commonly prescribed to treat high blood pressure and BPH. However, they may also be prescribed for CP/CPPS. That鈥檚 because the prostate and bladder are rich in alpha receptors. By blocking these cellular structures, alpha blockers help relax muscles in the prostate and urinary tract, allowing urine to flow more freely.

Four randomized, placebo-controlled trials initially demonstrated the effectiveness of alpha blockers in easing the symptoms of CP/CPPS, based on the NIH鈥揅hronic Prostatitis Symptom Index (see Figure 1, above). A 2003 study randomly assigned 86 men with CP/CPPS to receive either terazosin (Hytrin) or a placebo for 14 weeks. Of participants taking the drug, 60% had a greater than 50% drop in their average symptom score, compared with 37% for participants taking a placebo. A subsequent study by the same researchers concluded that the beneficial effect lasted up to 38 weeks.

Another 2003 study evaluated the effectiveness of alfuzosin (Uroxatral) in 37 men diagnosed with CP/CPPS who were randomly assigned to receive either the drug or a placebo. After six months, the men who took alfuzosin had a statistically significant drop in their symptom score compared with the men who took a placebo. At that point, therapy was discontinued, and over the next six months, the beneficial effect of alfuzosin wore off.

In 2004, researchers tested the alpha blocker tamsulosin (Flomax) in 58 men with CP/CPPS who randomly received either the drug or a placebo for six weeks. As a group, the men treated with tamsulosin experienced statistically significant improvement in their symptoms compared with the men who received the placebo. The effect was greater in men with moderate-to-severe CP/CPPS than in those with mild symptoms.

Another study compared tamsulosin, the antibiotic ciprofloxacin (Cipro), both drugs together, and a placebo. In contrast, this trial found no benefit from the alpha blocker. Researchers speculated that the lack of improvement was due to the fact that many participants had had symptoms for a long time and had previously tried several treatments, including alpha blocker therapy. (See 鈥淎lpha blocker research.鈥�)

Given the contradictory findings of the studies, as well as the fact that the studies were small, the Chronic Prostatitis Collaborative Research Network (CPCRN), which includes dozens of researchers, launched a larger randomized, placebo-controlled trial of alfuzosin. Two hundred and seventy-two men from the United States, Canada, and Malaysia enrolled in the trial. They were randomly assigned to take 10 milligrams (mg) of alfuzosin per day or a placebo for 12 weeks. Participants who had previously taken alfuzosin or another alpha blocker were excluded from the study. The result: alfuzosin was no better than a placebo in treating CP/CPPS. In both groups, 49.3% of the men had a decrease of at least four points in their total NIH鈥揅hronic Prostatitis Symptom Index score. The findings were published in The New England Journal of Medicine in December 2008. (See 鈥淎lfuzosin for CP/CPPS?鈥�)

The news was surprising and disappointing to urologists and their patients. Experts had thought that alfuzosin would probably be the most effective of the alpha blockers in treating CP/CPPS. But doctors continue to prescribe the medication because they have so few pharmacological options to offer patients. That may change, however.

On the horizon

Researchers are assessing the effectiveness of two other drugs 鈥� silodosin (Rapaflo) and pregabalin (Lyrica) 鈥� for the treatment of CP/CPPS. And nontraditional techniques, including biofeedback, which involves becoming more aware of the body鈥檚 signals, and myofascial trigger release, a type of massage therapy, are bringing much-needed relief to some medically savvy men. But most patients know little about these options.

Harvard鈥檚 Dr. O鈥橪eary is a urologist at Brigham and Women鈥檚 Hospital in Boston and a professor of surgery at Harvard Medical School. He is one of the world鈥檚 foremost authorities on CP/CPPS, and one of the researchers involved in the CPCRN, a consortium funded by the National Institute of Diabetes and Digestive and Kidney Diseases. In this interview, conducted in August 2009, Dr. O鈥橪eary talks about clinical trials under way for CP/CPPS and explains why biofeedback and myofascial trigger release might be worth looking into.

Lots of physicians were surprised by the outcome of the alfuzosin study. We were not expecting a negative result. Was the study poorly designed?

I think it was a well-designed trial. I may be biased because I鈥檓 one of the authors of the study, but The New England Journal of Medicine doesn鈥檛 publish poorly designed trials. My explanation is that alfuzosin just doesn鈥檛 work. As you know, we found that the placebo was just as effective as the drug at relieving symptoms. We did assess a number of secondary outcomes, such as general pain, urinary urgency, anxiety and depression, and erectile function. But the only difference we found between the two groups was in ejaculatory function, which improved significantly in the alfuzosin group. Otherwise, it was a completely negative trial 鈥� and another trial suggesting that alpha blockers probably don鈥檛 work.

Are any other drug trials under way at the moment for prostatitis?

We鈥檙e doing one right now on a drug called silodosin (Rapaflo), which is another alpha blocker. It鈥檚 being funded by a pharmaceutical company, and I鈥檓 a little surprised that they decided to go through with it after they saw the negative results of the alfuzosin trial and some negative findings related to tamsulosin. But it鈥檚 a brand-new drug and we really don鈥檛 have a lot of data on it. That might be why they are moving ahead with it.

Has the trial started? How many men do they hope to enroll?

The trial started in the fall of 2008, and the researchers aim to enroll 150 men who have had pelvic pain for at least three months. As with the alfuzosin study, men who have previously taken alpha blockers aren鈥檛 eligible. And it鈥檚 also a multicenter, double-blind, placebo-controlled trial. Participants will receive either 4 or 8 mg of silodosin or a placebo daily for 12 weeks. After that, the researchers will look at changes in the total symptom score. They will also look at changes related to pain and urinary symptoms, but those are secondary outcomes. I鈥檓 not involved in the trial, but we have enrolled a few patients in it.*

It will be interesting to see what happens, given that the other large alpha blocker studies have been negative.

That鈥檚 true. But I should say that I still prescribe alfuzosin even though the placebo response rate was so high. After all, what have you got to lose? These men are in pain, and they don鈥檛 have many other options at the moment.

Are researchers studying any other drugs that might ease prostatitis symptoms?

Yes. There鈥檚 the pregabalin (Lyrica) trial. Pregabalin is used to treat fibromyalgia.

People with fibromyalgia experience pain and stiffness in tendons, ligaments, and muscles, perhaps because of overly active nerves. What does that have to do with prostatitis?

Many experts hypothesize that severe, abnormal tension and overly active nerves in the muscles of the pelvic floor [see Figure 2] could explain the pain, discomfort, and urinary problems associated with prostatitis. Given that pain and muscle stiffness are symptoms of both conditions, and that pregabalin is effective in treating fibromyalgia, it seemed worth trying in men with prostatitis.

Tell us about the trial. Any encouraging findings?

Like the other trials I鈥檝e mentioned, it was a randomized, double-blind, placebo-controlled trial. We randomly assigned 324 men with pelvic pain for at least three of the previous six months to receive either pregabalin or a placebo daily for six weeks. The dose started at 150 mg, increased to 300 mg after two weeks, and then finally to 600 mg two weeks after that. The primary endpoint was a drop of at least six points in the total score on the NIH鈥揅hronic Prostatitis Symptom Index. After six weeks, 47.2% of the men assigned to take the drug reported a drop of at least six points in their total symptom score compared with 35.8% of the men assigned to take the placebo. That鈥檚 not a statistically significant difference, so technically, the trial was negative.

But it was positive for a number of the secondary endpoints. For example, 31% of the men who took pregabalin reported that their condition had markedly or moderately improved from the start of the trial, compared with just 19% of the men in the placebo group. The pregabalin group also showed more improvement than the placebo group in terms of pain. That was really encouraging. It suggests that pregabalin may be effective in some men with prostatitis. This was another CPCRN study. The findings were presented at the American Urological Association鈥檚 annual meeting in April 2009.

Do you prescribe pregabalin to your patients?

You bet 鈥� you鈥檝e got nothing to lose by trying it. Virtually every patient I see who鈥檚 already been to another physician has been given long courses of antibiotics; that just doesn鈥檛 work. So we try alpha blockers, and if they don鈥檛 work, we try pregabalin. I use pregabalin for patients who mainly experience pain because that was one of the secondary endpoints of the trial that was positive.

Do you have any trouble getting insurance companies to cover the cost?

Yes, absolutely. Pregabalin isn鈥檛 approved for the treatment of prostatitis, so insurance won鈥檛 cover it. It鈥檚 not cheap.* But most of the men I see are so miserable that they鈥檙e willing to try it and pay for it themselves.

What about nonpharmacological therapies?

I don鈥檛 know very much about biofeedback. I have had some patients who鈥檝e tried it. As far as I know, they鈥檝e had no great successes in terms of controlling pain. But the patients who are dysfunctional voiders definitely benefit from a behavioral technique like biofeedback. The challenge is to find professionals who know how to do it properly.

There has been growing interest in myofascial trigger release, or the so-called Stanford protocol, since the publication of a case study analysis back in 2005 in The Journal of Urology, which just published results of another study on it in the August 2009 issue. It wasn鈥檛 a large study 鈥� only 47 participants 鈥� and women were included, because they can develop chronic pelvic pain syndrome, too. Participants were randomly assigned to have weekly sessions of either traditional massage or myofascial therapy for 10 weeks. Although their goal was to determine whether such a study would generate solid data that might be the basis for a larger trial, the researchers also made some interesting observations. For example, 57% of those who received myofascial therapy reported that they were 鈥渕arkedly improved鈥� or 鈥渕oderately improved鈥� versus just 21% in the group that received ordinary massage. [See 鈥淢yofascial physical therapy for CP/CPPS.鈥漖

I don鈥檛 know whether they鈥檒l find funding for a full-scale trial of myofascial therapy, but these results were definitely encouraging. And I鈥檝e had a number of patients who say the treatment is definitely beneficial.

What criteria do you use to refer patients for myofascial therapy?

I鈥檓 willing to refer almost anyone who is suffering with chronic pelvic pain and hasn鈥檛 responded to standard pharmacological therapy 鈥� and that鈥檚 a lot of people. There simply isn鈥檛 much that works, so this is cause for optimism.

Originally published October 2009; last reviewed Feb. 23, 2011.