The Prostatitis Foundation
 

Prostatitis Research at the American Urological Association Meeting 2003

The American Urological Association’s 2003 Annual Meeting included research presentations on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in a poster session on infections and inflammation of the prostate, urethra, and genitalia, as well as in other poster sessions.

During a typical poster session, researchers’ work is mounted on poster boards throughout a conference room. Attendees can view these exhibits and talk with the researchers about their studies. Then, one researcher (designated by the asterisk) from each team gives a brief presentation of they study and answers questions from the audience.

This year, research addressed possible causes, diagnosis, classification and characterization of the disease, symptoms and quality of life, and potential treatments.

CAUSES
Infection?

LEVELS OF 16S BACTERIAL DNA IN SEMEN BY REAL TIME PCR DO NOT CORRELATE WITH CLINICAL DIAGNOSIS OR TREATMENT RESPONSE IN CATEGORY III CHRONIC PROSTATITIS
Daniel A. Shoskes*, Chantale Lapierre, Weston, FL; Scott Zeitlin, Los Angeles, CA

Could CP/CPPS be caused by some bacteria that just can’t be grown in a culture? These researchers used a different way of looking for evidence of bacteria in semen; instead of trying to grow bacteria, the researchers measured the amount of one kind of genetic material from bacteria. In 28 men who had CP/CPSS, 22 had detectable genetic material from bacteria, but the amount of material didn’t correspond with anything about their condition before treatment, including white cell counts and conventional cultures. Fifteen of the 28 men were given antibiotics, and of those, 7 improved; 8 of the 28 got quercetin, and of those, 7 improved, but again, there was no correlation with improvement and levels of bacterial genetic material in the semen. These investigators think that antibiotics could have helped the men either because they killed bacteria or because they had anti-inflammatory effects.

THE 2001 GIESSEN COHORT STUDY ON PATIENTS WITH CPPS/CP - AN EVALUATION OF INFLAMMATORY STATUS AND EVIDENCE OF BACTERIA 10 YEARS AFTER A FIRST ANALYSIS

Henning Schneider*, Martin Ludwig, Hamid M. Hossain, Thorsten Diemer, Wolfgang Weidner, Giessen, Germany

These German researchers looked for infectious bacteria of various kinds in men with symptoms of prostatitis. Of the 168 men they saw, 81% met the criteria for CP/CPPS. Only seven men (4%) had evidence of chronic bacterial prostatitis. Although the researchers found many different kinds of bacteria in low numbers in the men with symptoms, true chronic bacterial prostatitis was rare. In addition, there was little evidence of sexually transmitted microorganisms.

DOES ABACTERIAL PROSTATITIS REALLY EXIST?
Federico Guercini*, Rome, Italy; Sandra Mazzoli, Florence, Italy; Elisabetta Costantini, Cinzia Pajoncini, Massimo Porena, Perugia, Italy

These researchers think that hard-to-find-and-eliminate infections could cause what looks like chronic abacterial prostatitis. When they tested 56 men diagnosed with abacterial prostatitis with urethral swabs, they found no infection. But then the clinicians took samples directly from the men’s prostates and found infectious organisms in 79% of them. Twenty one men (38%) had more than two species of microorganisms identified, and 9 (15%) had more than three.

Estrogen exposure/autoimmune disease?

PROSTATITIS INDUCED BY EARLY ESTROGENIC EXPOSURE IN THE RAT IS PARTIALLY BLOCKED BY PROLACTIN SUPPRESSION
Jason Gilleran*, Gail Prins, Oliver Putz, Chicago, IL

Abnormal exposure of the prostate to estrogen and prolactin are thought to play a role in chronic prostatitis, possibly by bringing about a kind of autoimmune response. This kind of hormone exposure has been associated with autoimmune diseases in other contexts. These researchers exposed rats at birth to an inert oil or an estrogen, then right before puberty, some were given a drug that suppresses the hormone prolactin and others to a placebo. The researchers looked at the size of the prostate lobes, testes, spleen, adrenal glands, and thymus glands in adulthood and also the structure of the prostate glands, the animals’ immune responses, and white blood cell populations. The rats exposed to estrogen who got the prolactin-suppressing drug didn’t have different organ sizes but did show that the inflammatory response of their white blood cells was partially suppressed. All the rats exposed to estrogen early, regardless of whether prolactin was suppressed, had abnormal-appearing epithelial cells in the prostate as adults. There may be an effect of estrogen on the prostate. The researchers think that early, abnormal estrogen exposure may affect inflammation and immune cell infiltration of the prostate gland in men.

Genetic?

POSSIBLE FUNCTION OF SHORT TANDEM REPEATS FOR GENETIC TESTING IN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME PATIENTS
Donald Riley*, John Krieger, Seattle, WA

These researchers found some evidence that men who get CP/CPPS may have a genetic predisposition to it. The DNA sequences called short tandem repeats (STRs) near the androgen receptor gene may be involved. The study showed that these STRs may actually perform a function in cells, pointing to their potential role.

DIAGNOSING, CLASSIFYING, AND CHARACTERIZING PROSTATITIS

MALE INTERSTITIAL CYSTITIS—TIME FOR A CHANGE?
Jordan D Dimitrakov*, Plovdiv, Bulgaria; Dorian Y. Dikov, Lagny-sur-Marne Cedex, France

Do men with nonbacterial prostatitis and prostatodynia really have interstitial cystitis instead? Previous studies using cystoscopy with hydrodistention have shown that up to 70% of men with these diagnoses have bladder abnormalities that meet the NIH-NIDDK criteria for IC. These researchers tested 300 men with confirmed chronic pelvic pain for interstitial cystitis. Testing included cystoscopy with hydrodistention, the potassium sensitivity test, and measurements of potential markers of interstitial cystitis in prostatic secretions and urine. Those markers included nerve growth factor (NGF), tryptase, heparin-binding epidermal growth factor-like growth factor (HB-EGF), and epidermal growth factor (EGF). Of the 300 men, 240 (80%) had interstitial cystitis, confirmed by the characteristic glomerulations seen on the bladder wall during cystoscopy with hydrodistention. All patients with interstitial cystitis had some degree of erectile dysfunction and burning or pain during and/or after ejaculation. The levels of NGF and tryptase were significantly higher and the HB-EGF levels were significantly lower in the interstitial cystitis patients than in with healthy controls. NGF, HB-EGF, and tryptase may be promising new markers for evaluating men with pelvic pain. Any young man who has burning and/or pain after ejaculation should be evaluated for interstitial cystitis, say these researchers.

EVALUATION OF THE CYTOKINES MACROPHAGE INFLAMMATORY PROTEIN-1 ? AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 AS INDICATORS OF INFLAMMATION IN PROSTATIC SECRETIONS
Jeffrey A. Stern*, Alisa E Koch, Phillip L. Campbell, Anthony J. Schaeffer, Chicago, IL

Certain proteins secreted by immune system cells, called cytokines, may play a role in inflammation. Measuring the levels of some cytokines, say these researchers, could help provide an objective way to measure inflammation. Specifically, they looked at levels of macrophage inflammatory protein-1? (MIP-1?) and monocyte chemoattractant protein-1 (MCP-1) in expressed prostatic fluid of healthy men and men with inflammatory and noninflammatory chronic pelvic pain syndrome (CPPS). These cytokines are known to increase the activity of or attract different types of white blood cells. Although they found both cytokines in all the groups, levels were highest in men with inflammatory CPPS. There was no difference in levels between men with noninflammatory CPPS and the control group for either cytokine. These cytokines, say the researchers, may play a role in recruiting the white blood cells that flock to the inflamed prostate.

THE USE OF INTRAPROSTATIC NITRIC OXIDE MEASUREMENTS TO DIFFERENTIATE BETWEEN INFLAMMATORY AND NON-INFLAMMATORY ABACTERIAL CHRONIC PROSTATITIS.
Abolfazl Hosseini*, Ingrid Ehrèn, Peter Wiklund, Stockholm, Sweden

The NIH classification of chronic prostatitis distinguishes between inflammatory and noninflammatory types. Often, the only way to determine whether inflammation is present is to look for white blood cells in prostatic secretions in urine obtained through prostatic massage and the “four-glass” test. These researchers tried another way to measure inflammation—looking for levels of nitric oxide (NO) gas in the portion of the urethra in the prostate by collecting samples of air there in a catheter. Levels of the gas have been used to judge the degree of inflammation in other problems, such as asthma, colitis, rheumatoid arthritis, and lower urinary tract inflammation. The levels of NO did, indeed, correlate with amount of white cells.

SEMINAL MARKERS OF INFLAMMATION IN CHRONIC PELVIC PAIN SYNDROME (CPPS): SUGGESTION FOR APPROPRIATE CUTPOINTS
Martin Ludwig*, Andreas Vidal, Thorsten Diemer, Wolfgang Pabst, Klaus Failing, Wolfgang Weidner, Giessen, Germany

Is there an easier way to distinguish inflammatory from noninflammatory prostatitis than looking for white blood cells in prostate secretions in urine obtained with prostatic massage and the “four-glass” test? These researchers looked for white blood cells and levels of elastase, an inflammation marker, in ejaculate and compared the results with those of the four-glass test. The two types of tests correlated well, helping distinguish inflammatory from noninflammatory prostatitis. On the other hand, they concluded that the World Health Organization (WHO) cutoff for having significant amounts of white blood cells in the ejaculate is too low. These researchers think it should be 0.113 million/mL peroxidase-positive leukocytes (PPL) rather than the WHO’s 1 million/mL. The elastase level also correlated well with the PPL count.

TOTAL PROSTATE-SPECIFIC ANTIGEN IS ELEVATED AND STATISTICALLY, BUT NOT CLINICALLY SIGNIFICANT IN PATIENTS WITH CHRONIC PELVIC PAIN SYNDROME/PROSTATITIS
Robert B. Nadler*, Anthony J. Schaeffer, Chicago, IL; Jill S. Knauss, Kathleen J. Propert, Richard Landis, Philadelphia, CA; Stephen D. Mikolajczyk, San Diego, CA; Richard B. Alexander, Baltimore, MD

Prostate-specific antigen (PSA) levels don’t indicate whether a man has CP/CPSS, and if a man does have a high PSA, he should be evaluated for prostate cancer, say these researchers. They looked at three different PSA measurements (total, free, and percent free) in 424 CP/CPSS patients and 114 men the same age with no symptoms. Total PSA was slightly higher in men with CP/CPSS, but there were no real differences in any other measurement.

SYMPTOMS AND QUALITY OF LIFE

PAIN AND AFFECTIVE DISTRESS AS PREDICTORS OF QUALITY OF LIFE IN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS)
Dean A. Tripp*, J. Curtis Nickel, Kingston, ON, Canada; Richard J. Landis, Jill S. Knauss, Philadelphia, PA; and the CPCRN, Bethesda, MD

Researchers at seven different centers in the United States and Canada looked at how psychological factors and physical symptoms affect the quality of life in men CP/CPSS. The 488 men studied were enrolled in the NIH Chronic Prostatitis Cohort (CPC) study. The most important factors in qualify of life were the degree of urinary symptoms, psychological distress, and pain, with pain topping the list. Psychological distress came in second. The man’s age and whether he was living with a partner weren’t significant factors in quality of life. These researchers say it is important to learn how psychological distress and pain are related for men with CP/CPSS.

SEXUAL DYSFUNCTION IN YOUNG PATIENTS WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME
Juza Chen*, Alexander Greenstein, Mario Sofer, Haim Matzkin, Tel-Aviv, Israel

Many symptoms of CP/CPPS are well described, but it isn’t known how much younger men with CP/CPPS may suffer with sexual dysfunction. In 147 patients with CP/CPPS aged 18 to 50 years (average 30 years) in Israel, 95 said they had some degree of erectile dysfunction. Fifty-two had ejaculatory dysfunction, 30 had pain during ejaculation, 25 had premature ejaculation, and 5 had unejaculation. Forty seven patients said their sexual satisfaction was impaired and 40 said they had decreased sexual arousal. This degree of sexual dysfunction is above what is expected for this age group.

TREATMENT

LEVOFLOXACIN TREATMENT FOR CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS) IN MEN: A RANDOMIZED PLACEBO CONTROLLED MULTICENTER TRIAL
J. Curtis Nickel*, Joe Downey, Janet Clark, and The Canadian Prostatitis Research Group, Kingston, ON, Canada

Do antibiotics work for CP/CPSS? A multicenter Canadian study aimed to find out. Sixty five men who had CP/CPSS (that is, no infection identified in the prostate), were included in the study. Their ages ranged from 36 to 78 years (average 56), and they had had symptoms for as little as 7 months and as long as 32 years (average about 7 years). For six weeks, 36 men were given 500 mg/day of the antibiotic levofloxacin (Levaquin), and the other 29 were given a placebo. The researchers looked at how they rated their symptoms at 3, 6, and 12 weeks. The differences looked significant at the three-week mark, with levofloxacin recipients doing better, but after that, the difference between the groups wasn’t significant.

ALFUZOSIN TREATMENT FOR CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS): A PROSPECTIVE RANDOMIZED PLACEBO CONTROLLED STUDY
Aare Mehik*, Oulu, Finland; Peeter Alas, Oulainen, Finland; J. Curtis Nickel, Kingston, ON, Canada; Ari Sarpola, Pekka Hellstrom, Oulu, Finland

Alpha blockers, often used to treat benign prostate enlargement, help ease symptoms for men with CP/CPSS. These Finnish researchers had information from 61 patients to evaluate: 19 took the alpha blocker alfuzosin (Xatral, available in Europe and not the United States), 16 took a placebo, and 26 underwent standard therapy for six months, and then were followed up six months later. The patients rated their symptoms using the Chronic Prostatitis Symptom Index (CPSI). After six months of therapy, the men taking alfuzosin had a significantly better reduction in pain than the men in the other two groups, but there wasn’t a significant difference between the groups in terms of voiding or quality of life scores. Six months later the condition of the men in the alfuzosin and placebo groups deteriorated compared with that of the men undergoing standard therapy. Side effects of the alfuzosin therapy were mild, with mild gastrointestinal symptoms and a decrease in the volume of ejaculate for a few of the men. The researchers concluded this alpha blocker offers modest but real benefits and that it takes several months for the benefits to appear.

LONG-TERM EFFECTIVENESS OF TERAZOSIN THERAPY FOR CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS)
Phaik Yeong Cheah, Men Long Liong, Kah Hay Yuen, Wing Seng Leong*, Chu Leong Teh, Timothy Khor, Penang, Malaysia; Jin Rong Yang, Kuala Lumpur, Malaysia; Hin Wai Yap, Penang, Malaysia; John N Krieger, Seattle, WA

The alpha blocker terazosin (Hytrin) seems to help men with CP/CPSS avoid relapse. In this study, men had already been participated in a 14-week blinded study of the alpha blocker versus placebo. Then, the men who didn’t respond to therapy or who had a relapse got further therapy with either terazosin or standard treatment (not in a blinded fashion) and were followed up for another six months. Five of 23 men who took terazosin (22%) had a relapse, whereas 6 of 12 men (50%) who took placebo had a relapse. In addition, in those who didn’t respond to treatment before or who had had a relapse, the men who got additional terazosin had about a threefold better chance of improving than men who chose no further treatment.

MYCOPHENOLATE MOFETIL IN THE TREATMENT OF CPPS: A DOUBLE-BLIND PLACEBO-CONTROLLED STUDY
Jordan D. Dimitrakov*, Plovdiv, Bulgaria; Dorian Y. Dikov, Lagny-sur-Marne Cedex, France

Because they had read about clinicians having some success treating chronic prostatitis with an immunosuppressive drug, these researchers decided to study the drug, mycophenolate mofetil (CellCept), more formally in 200 men with CPPS. This drug is usually used to combat rejection in kidney transplant patients. One group of men received the drug 500 mg twice daily for 4 weeks, and the other group got placebo. The ones who got the drug did significantly better: After one month, 85% of the men who received mycophenolate mofetil said their pain was improved, compared with 25% of the men who got the placebo. Six months later, 65% of the men who got the drug said they were still better, compared with only 15% of those who got the placebo. In addition, the levels of proinflammatory cytokines, which are proteins involved in inflammation, were decreased significantly in the men who received mycophenolate compared with the men who got placebo. Side effects were mild and well-tolerated, including headache, transitory skin rash, and nausea.

MULTICENTER AUSTRIAN TRIAL ON SAFETY AND EFFICACY OF PHYTOTHERAPY IN THE TREATMENT OF CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME
Andreas Reissigl*, Josef Pointner, Bregenz, Austria; Michael Marberger, Mesut Remzi, Vienna, Austria; Juergen Brunner, Stefan Obwexer, Bregenz, Austria; Bob Djavan, Vienna, Austria

European researchers tested a saw palmetto (Serenoa repens) extract, called Permixon, on men with CP/CPPS symptoms. (Permixon is used in Europe for benign prostatic hyperplasia or BPH.) Although the men who got Permixon were better for a while after the therapy ended, the effects didn’t last long-term. Thirty-two men received the extract for 6 weeks, and 24 did not. Researchers looked at how the men were doing 6 and 12 weeks after that based on the patients’ overall assessment, scores on the NIH Chronic Prostatitis Symptom Index (CPSI), safety data, PSA levels, and prostate volume. Overall, 75% of the men who got Permixon had at least mild improvement, compared with 20% of the control group, and 55% of Permixon patients said they had moderate or marked improvement compared with 16% of the control patients. At 6 weeks, Permixon patients showed a 30% reduction in their total NIH-CPSI scores, but at 12 weeks, there was no difference between the groups. Prostate volume did not change significantly in either group. In the control group, PSA did not differ from baseline, but Permixon patients had a median decrease in PSA of 22% at 6 weeks. It seems that this treatment may be helpful, and if men do get benefit from it, they may need to keep taking it.

COOLED THERMOTHERAPY (TUMT) FOR CHRONIC ABACTERIAL PROSTATITIS 6 MONTHS AFTER TREATMENT
Christof Kastner*, Redhill, Surrey, UK; Werner Hochreiter, Berne, Switzerland; Juan Cabezas, Christian Huidobro, Santiago, Chile; Paul D. Miller, Redhill, UK

Transurethral microwave thermotherapy of the prostate as a treatment for CP/CPPS has been only variable successful. A newer kind of thermotherapy with a system that cools the urethra to control was tried in 40 patients who had had intractable symptoms for the last three to six months. For one patient, therapy was stopped because of pain, but better pain killers then allowed him to undergo therapy later. Thirty five of the 40 patients had had a 6-month evaluation at the time of the study, and for them, the mean pain score on the NIH Chronic Prostatitis Symptom Index (CPSI) went from 11.3 before treatment to 3.5, the urinary score went from 4.7 to 2.2, and the quality of life score from 7.2 to 3.1—all statistically significant improvements. Only two patients had any score that got worse by more than one point. Complications were called minimal and transient, including urinary tract infection, acute urinary retention, and lower urinary tract symptoms early after treatment. One case of dry orgasm was reported. The other patients either stayed the same or improved in terms of fertility, sexual activity, libido, and erectile function. A larger trial is being planned to see if the effects last.

 

 

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