This year, researchers presented nearly 20 studies that improved our picture of how common chronic nonbacterial prostatitis (chronic pelvic pain syndrome or CPPS) is, pointed the way toward new CPPS therapies and diagnostic techniques, demonstrated the impact of CPPS on men’s mental health and sex lives, continued the search for the cause of CPPS, and helped clarify the cause of bacterial prostatitis.
HOW COMMON IS CPPS?
INCIDENCE AND CLINICAL CHARACTERISTICS OF NIH TYPE III PROSTATITIS IN A MANAGED CARE POPULATION
J. Quentin Clemens, Chicago, IL; Richard T. Meenan, Maureen C. O’Keeffe Rosetti, Sara Y. Gao, Portland, OR; Elizabeth A. Calhoun, Chicago, IL
Researchers estimated the incidence of chronic prostatitis type III (chronic pelvic pain syndrome or CPPS) in the population to be 3.0 per 1,000 men per year, according to their analysis of records of an HMO population.. This incidence is very close to the incidence of 3.1 per 1,000 person-years reported in a 1998 study. When men without pain symptoms were excluded from this analysis, the incidence was 2.6 per 1,000 person-years. If those who had symptoms for less than 3 months were excluded, the incidence was 1.2 per 1,000 person-years. The researchers determined the incidence by looking at the number of claims with the codes for “chronic prostatitis” and “prostatitis not otherwise specified” and also confirming the diagnoses in the actual medical charts of a sample of those men. The team then categorized the type of prostatitis diagnosed based on the NIH definitions: type I/II (caused by infection), type III (based on at least one of the pain or urinary symptoms in the NIH-Chronic Prostatitis Symptom Index [CPSI]), or type IV (inflammation that happens to be found in a prostate biopsy sample when a man has no symptoms). Among the 303 men who got their diagnoses in the HMO, 58 had type I/II, 198 had type III, 33 had type IV, and 23 didn’t fit the categories. Prostatitis, the researchers concluded, is a common condition.
ARE URINARY TRACT INFECTIONS ASSOCIATED WITH PROSTATITIS SYMPTOMS: RESULTS FROM THE BOSTON AREA COMMUNITY HEALTH (BACH) SURVEY
Nicholas A. Daniels, San Francisco, CA; Carol L. Link, Watertown, MA; Michael J. Barry, Boston, MA; John B. McKinlay, Watertown, MA
Prostatitis symptoms occur in about 4% of men age 30 to 79 years and correlate strongly with a history of urinary tract infection (UTI) and age, according to an analysis of the Boston Area Community Health (BACH) survey. Race—black, white, Hispanic—and socioeconomic status make no difference. This analysis included the first 1,559 men that age who answered questionnaires, which included pain and urinary symptom questions from the NIH-CPSI. Of those men, 79 reported symptoms. Among those age 30 to 39 years, 1.22% had symptoms; of those 40 to 49, 2.21% had symptoms; in the 50 to 59 group, 8.08% had symptoms; and in the 60 to 79 group, 7.72% had symptoms. That meant that 30- to 39-year-olds had 0.16 times the odds of 60- to 79-year-olds of having prostatitis symptoms. Of men who had had a UTI, 12.60% had prostatitis symptoms versus 2.98% who had not had UTIs, giving those who had UTIs 3.8 times greater odds of having prostatitis symptoms.
MIP-1α AND MCP-1: NOVEL BIOMARKERS FOR CHRONIC PROSTATITIS
Jeffrey A. Stern, Chicago, IL; Alisa E. Koch, Phillip L. Campbell, Ann Arbor, MI; J. Richard Landis, Philadelphia, PA; Anthony J. Schaeffer, Chicago, IL
Two cytokines could become useful biomarkers for diagnosing CPPS. These researchers found that levels of the two cytokines in expressed prostatic secretions from men with CPPS distinguish them from healthy men. Known as macrophage inflammatory protein-1α (MIP-1α) and monocyte chemoattractant protein-1 (MCP-1), these cytokines may also play a role in the actual disease process. MIP-1α attracts the types of white blood cells known as a macrophages and T lymphocytes, and MCP-1 attracts mononuclear phagocytes. The researchers looked for these two cytokines in specimens from 12 healthy men, 25 men with category IIIA prostatitis or inflammatory CPPS (who show white blood cells in the specimens), and 28 men with type IIIB prostatitis or noninflammatory CPPS. The mean levels of MIP-1α in those groups were 148.88 pg/mL, 1162.85 pg/mL, and 1384.05 pg/mL, respectively, and the mean levels of MCP-1 were 599.43 pg/mL, 3302.21 pg/mL, and 1927.88 pg/mL, respectively. The levels in both CPPS groups were significantly higher than in the healthy men. Using a cutoff point of 69.99 pg/mL for MIP-1α and a cutoff point of 1061.84 for MCP-1 yielded a sensitivity of 88.7% and specificity of 80% for detecting CPPS.
VALIDATION OF THE PRE AND POST MASSAGE TEST (PPMT) FOR THE EVALUATION OF THE PATIENT WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS)
J Curtis Nickel, Kingston, ON, Canada; Yanlin Wang, Philadelphia, PA; Daniel Shoskes, Weston, FL; Kathleen Propert, Philadelphia, PA; The NIH Chronic Prostatitis Collaborative Research Network, Bethesda, MD
The classic Meares-Stamey four-glass test is a standard for assessing the inflammatory and microbiological status of the lower urinary tract in men who have chronic prostatitis symptoms. Nevertheless, it’s almost never used except in research settings, mainly because of the time and expense. But it is important for urologists to look for bacteria and white blood cells when they’re trying to make a diagnosis so they can prescribe antibiotics or anti-inflammatory agents appropriately. For this reason, NIH Chronic Prostatitis Collaborative Research Network investigators compared an easier method with the traditional method to see if the easier-to-perform test would still be useful. Whereas the traditional test includes bacterial cultures of initial voided urine (VB1), midstream urine (VB2), expressed prostatic secretions (EPS), and a postprostatic massage urine specimen (VB3), the simplified test includes cultures of just EPS and VB3. The researchers looked at data from 353 men who enrolled in the NIH Chronic Prostatitis Cohort (CPC) study and had complete data on the four-glass test. They compared the results of all four cultures with the those from just EBS and VB3 specimens. In 96% to 98% of cases, the simplified test came up with the same results as the classic test. The simplified test, by definition, had high (100%) specificity (in other words, very good at identifying white cells and bacteria) but had lower (75%) sensitivity than the classic test (in other words, not as good at picking up white cells and bacteria in everyone who had them). Even though the sensitivity is lower, the researchers concluded that this simplified test is a reasonable one for community physicians to do when they are first trying to diagnose and decide how to treat men with chronic prostatitis symptoms.
THE STANFORD PROTOCOL FOR MALE PELVIC PAIN: INTEGRATION OF MYOFASCIAL TRIGGER POINT RELEASE AND PARADOXICAL RELAXATION TRAINING
Rodney U. Anderson, Christine Chan, Stanford, CA; Timothy Sawyer, Los Gatos, CA; David Wise, Sebastopol, CA
This team evaluated a new approach to treatment of CPPS with the Stanford University-developed protocol of physical therapy (myofascial muscular release) directed mainly at the pelvic floor in conjunction with a cognitive behavioral therapy called paradoxical relaxation. In this type of relaxation training, patients focus on their tension, yet try to relax from it. The team treated 138 men with CPPS not helped by other treatments with this approach as the only therapy for at least one month. Patients had physical therapy weekly and had individual instruction in the relaxation technique weekly for up to 8 weeks with a recommendation for daily home practice with instructional audiotapes. The team assessed how the men were doing with the NIH-CPSI, a Pelvic Pain Syndrome Survey (PPSS), and the Global Response Assessment (GRA) questionnaire. More than half of patients treated with this protocol had clinical improvements and a 25% or better decrease in pain and urinary symptom scores assessed by the PPSS. Among men who had at least 50% improvement, median scores decreased 69% for pain and 80% urinary symptoms. Both scores decreased significantly by a median of 8 points when the 25%-or-better improvement was first seen. After a median of five treatments, GRA scores improved moderately or markedly for 72% of patients. Both the PPSS and NIH-CPSI scores showed similar levels of improvement after treatment. The median pretreatment NIH-CPSI total score of 24 decreased significantly—by a median of 11 points (46%) for patients who were markedly improved and by 8 points (24%) for those who were moderately improved. The researchers believe their study shows that this therapeutic protocol can give men with CPPS pain and urinary symptom relief comparable with that of traditional therapy.
ANTI-NANOBACTERIAL THERAPY IN MEN WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME AND PROSTATIC STONES
Daniel Shoskes, Kim Thomas, Eyda Gomez, Weston, FL
Often, patients with CPPS have prostatic stones, but the link with symptoms has been unclear. Nanobacteria, however, have been implicated in causing these stones. In 16 men with CPPS and these types of stones who didn’t get better with other treatments, Dr. Shoskes and his team tried a treatment in a suppository that includes 500 mg of tetracycline, a proprietary blend of neutraceuticals, and EDTA (comET, Nanobac Life Sciences). The researchers were able to evaluate results in 15 men. Among those, NIH-CPSI scores improved significantly, declining from a mean of 25.7 to 13.7, with a decline in every symptom subgroup; 12 patients (80%) had at least 25% improvement and 8 (53%) at least 50% improvement. The researchers found nanobacterial antigens or antibodies in blood samples from 60% of the men and in urine samples from 40%. Among 10 patients who underwent transrectal ultrasound after therapy, stones shrank or disappeared in 5. It wasn’t clear whether the men improved because the stone-producing nanobacteria were affected or for some other reason. The investigators called for prospective, controlled trials.
THALIDOMIDE AS THERAPY FOR THE CHRONIC PELVIC PAIN SYNDROME (CPPS)
Federico Guercini, Elisabetta Costantini, Cinzia Pajoncini, Antonella Giannantoni, Massimo Porena, Rome, Italy
Many studies suggest that CPPS might have an autoimmune origin, including those that show men with CPPS have elevated levels of cytokines. Infliximab, etanercept, and thalidomide are cytokine-modulating drugs, but because the first two have severe side effects, this team decided to test thalidomide, which does not have severe side effects in men, as a CPPS treatment. They pitted the drug against placebo in men who had CPPS and abnormal levels of the cytokines IL2, IL6, IL8, IL10, and TNF-alpha in sperm. Fifteen patients received oral thalidomide 100 mg/day for 4 weeks, which was increased to 200 mg/day for 8 more weeks. Another 15 received placebo. The researchers assessed symptoms in the men with the NIH-CPSI at the start of the study and at 4, 12, and 16 weeks of follow up. Cytokine levels in the treatment group were significantly reduced throughout the follow up compared with baseline levels but didn’t change in the placebo group. Symptom scores, however, did not change significantly with treatment or with placebo.
CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME RECURRENCE AFTER INITIAL EFFECTIVE PHYTOTHERAPEUTIC TREATMENT
Andreas E. Reissigl, Bregenz, Austria; Bob Djavan, Vienna, Austria; Josef Pointner, Stefan Obwexer, Bregenz, Austria
Men with CPPS and no evidence of inflammation (type IIIB) who had been in a trial of treatment with Permixon (Serenoa repens or saw palmetto) were re-evaluated 3 years after their treatment. Although they had improvements at 6 and 12 months during the trial, those effects didn’t last over the long term after therapy was discontinued. Fifty-five of the 72 men in the original study answered the NIH-CPSI questionnaire. By 6 months, 78.2% of the men had at least mild (30% to 50%) improvement, and 71.8% did at 12 months, but only 32.5% showed that degree of improvement 3 years later. Also, by 6 months in the original study, 42.5% of the men had significant (50% or better) improvement, and by 12 months, 44.2% did, but only 19% had that level of improvement 3 years later. Short-term monotherapy doesn’t have a continuous effect in CPPS patients, the researchers concluded.
A RANDOMIZED-PLACEBO CONTROLLED PILOT STUDY OF TAMSULOSIN, NAPROXEN, AND COMBINATION IN CATEGORY IIIA/IIIB CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME
Richard D. Batstone, Redcliffe, Australia; Julie Lynch, Andrew Doble, Cambridge, United Kingdom
Contrary to current thinking in North America about the benefits of multimodal therapy for CPPS, these Australian and UK researchers did not find any benefit of combination therapy—at least the combination of the alpha blocker tamsulosin and the anti-inflammatory naproxen. After a 4-week washout period, 83 patients were randomized to receive placebo/placebo, tamsulosin (400 mcg daily)/placebo, naproxen (500 mg twice daily)/placebo, or tamsulosin/naproxen. Neither researchers nor patients knew which received which treatment. Researchers assessed how patients were doing with the NIH-CPSI and considered them to be responders by 25% and 50% improvements in the score. The median improvements in scores at 4 and 6 weeks were 2 and 3 points in the placebo group, 2.5 and 7 points in the tamsulosin group, 2 and 4.5 in the naproxen group, and 3 and 3 in the combination group. At 6 weeks, the number of patients with 25% and 50% responses, respectively, to treatment at 6 weeks were 4/20 and 1/20 in the placebo group, 6/20 and 3/20 in the tamsulosin group, 7/22 and 4/22 in the naproxen group, and 1/21 and 0/21 in the combination group. Patients did better with single agents than with the combination. In fact, the combination was no better than placebo. Also, those who took the combination had more adverse effects than the other men.
EFFICACY OF ALFUZOSIN 10MG OD IN MEN WITH LUTS, BPH AND PROSTATITIS-LIKE SYMPTOMS
J. Curtis Nickel, Kingston, ON, Canada; Mostafa Elhilali, Montreal, PQ, Canada; Guy Vallancien, Paris, France
Painful ejaculation is one of the most prevalent, differentiating, and bothersome symptoms in men with CPPS. These researchers studied the effects of the alpha blocker alfluzosin on this and other symptoms by comparing its effects in men with lower urinary tract symptoms (LUTS) alone with the effects in men who also had pain or discomfort with ejaculation. This open-label study (researchers and patients new they were getting the medication) of 4,857 sexually active men from Europe, Asia, Africa, Canada, Middle-East, Latin America assessed the effects of alfuzosin 10 mg/day over 6 months. Of those men, 997 (20.5%) had pain/discomfort on ejaculation and 889/997 (89.2%) considered it to be a problem. Under alfuzosin treatment, men with painful ejaculation had significantly greater improvements in LUTS (-8.3 vs -6.7), bother (-1.9 vs -1.4), and sexual dysfunction (-0.8 vs -0.3) than men without pain. Placebo-controlled studies, the researchers noted, are needed to confirm the beneficial effect of alfuzosin in CPSS.
PRACTICES FOR CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME: A NATIONWIDE POSTAL SURVEY OF UROLOGISTS IN SOUTH KOREA
Soo Woong Kim, Ja H. Ku, Jae-Seung Paick, Seoul, Republic of Korea
Urologists in South Korea do not follow textbook algorithms for diagnosis and treatment of CPPS, concluded these researchers who surveyed the country’s urologists. Of 850 randomly selected urologists, 302 returned surveys, and 275 surveys were used for analysis. Although more than 50% of the urologists believed that chronic prostatitis has a multifactorial etiology, 52% thought CPPS to be bacterial in nature, nevertheless. The most commonly used tests were urinalysis (95.3%), expressed prostatic secretions (89.5%), and digital rectal examination (81.1%). Only a few urologists used specific lower urinary tract cultures. Only 12.7% assessed symptoms with the NIH-CPSI. First choices for therapy included antibiotics (96.4%), alpha blockers (71.6%), and Sitz baths (70.5%). When initial treatment was unsuccessful, urologists often prescribed a second course of either alpha blockers (69.5%) or antibiotics (57.8%) anyway. Practices in university hospitals were much less likely than primary clinics to prescribe antibiotics as secondary treatment. The belief that cultures helped diagnose CPPS also influenced prescribing antibiotics as secondary treatment.
CONDITIONS ASSOCIATED WITH CPPS
CHRONIC PROSTATITIS IS AN INDEPENDENT RISK FACTOR FOR ERECTILE DYSFUNCTION
Stanley Zaslau, Dale Riggs, Barbara Jackson, Stanley Kandzari, Morgantown, WV
Chronic prostatitis is an independent risk factor for erectile dysfunction (ED), say these researchers, who based their conclusion on an Internet-based and in-clinic survey of chronic prostatitis patients, healthy patients, and patients who had other urologic problems, including ED. The survey used was the Sexual Health Inventory for Men (SHIM). Patients with chronic prostaitis had significantly lower total scores and also lower confidence that they could keep an erection than other patients. Patients with prostatitis (mean age 41.5 years) were younger than those seen for other urologic complaints (mean age 41 years) and older than healthy controls (mean age 25 years). The researchers recommended that chronic prostatitis patients should be asked about and offered treatment for ED in addition to their chronic prostatitis.
COPING WITH DEPRESSION IN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME: A KEY TO TREATMENT OF THE PAIN?
Dean Tripp, J. Curtis Nickel, Kingston, ON, Canada; Mary McNaughton-Collins, Boston, MA; Yanlin Wang, J. Richard Landis, Philadelphia, PA; The NIH Chronic Prostatitis Collaborative Research Network, Bethesda, MD
The most common comorbid disorder in chronic pain is depression. It is also a prominent and common, yet usually unrecognized, condition in men with CPPS. These researchers studied depression as well as “catastrophizing,” the degree of social support, and urinary symptoms and pain in 150 men with CPPS who were enrolled in the NIH Chronic Prostatitis Cohort study at seven tertiary care clinical centers. The researchers found that, although pain, catastrophizing, and social support strongly predicted depression, the pain coping factors added significantly to the depression after accounting for the other effects. In particular, pain guarding and asking for assistance were significant predictors of greater depression. Physicians treating men with CPPS may be able to advise patients to avoid the pain-coping strategies associated with greater depression.
WHAT CAUSES CPPS?
INCONSISTENT LOCALIZATION OF GRAM-POSITIVE BACTERIA TO PROSTATE-SPECIFIC SPECIMENS FROM PATIENTS WITH CHRONIC PROSTATITIS
Donald E. Riley, Susan O. Ross, Ajit P. Limaye, John N. Krieger, Seattle, WA
Some argue that Gram-positive bacteria, which are not the types that typically cause UTIs, play a role in causing chronic prostatitis because some studies have found large (more than 10-fold) increases of these types of bacteria in expressed prostatic secretions (EPS) or post-prostate massage urine (VB3) of patients. Others say that most of these bacteria don’t cause disease and would normally be there. This team checked for those types of bacteria in 130 cultures from 59 patients (who had no common sexually transmitted disease organisms and who had not taken antimicrobials or anti-inflammatory drugs recently). Thirty five of those cultures from 29 patients had 10-fold increases in Gram-positive bacteria. Among patients who had more than one set of cultures done, 39% had negative results, and 37% had inconsistent results. Among the patients who had more than two studies done, no one patient had the same type of bacteria show up in any of the studies. These investigators concluded that Gram-positive bacteria have only a limited role in causing chronic prostatitis. That’s consistent with their observation that Gram-positive bacteria have rarely been identified in prostate biopsy tissue from patients with chronic prostatitis symptoms.
Mn-SOD POLYMORPHISM IN CHRONIC PELVIC PAIN SYNDROME PATIENTS
Elif D. Buyuktuncer, Serdar Arisan, Murat Can Kiremitci, Hatice Tigli, Narcin Palavan Unsal, Turhan Caskurlu, Erbil Ergenekon, Istanbul, Turkey
A certain variant (called a polymorphism) in how a particular amino acid sequence of manganese superoxide dismutase (MnSOD) is coded genetically seems to occur more often in type IIIA CPPS patients than in healthy patients. Part of the DNA sequence for Mn-SOD has been associated with damage to mitochondria and some type of signal protein. These researchers think the Val(16)Ala polymorphism of Mn-SOD may play a role in causing CPPS.
INTRAPROSTATIC LYMPHOCYTES IN OLD WISTAR (W) RATS WITH SPONTANEOUS AND EXPERIMENTAL ESTROGEN-INDUCED PROSTATITIS (EEP)
Eugene V. Vykhovanets, Martin I. Resnick, Susan R. Marengo, Cleveland, OH
These researchers profiled the types of white blood cells that infiltrate the prostate, which might provide clues as to how spontaneous prostate inflammation develops. They used estrogen to induce a prostatitis in rats and also looked for spontaneous inflammation, which tends to occur in older animals. The profiles were similar in the two types of prostate inflammation. Specifically, the CD4+/CD8+ T-cell ratio was increased and levels of CD4+α/βTCR+CD161a+ NKT-cells were decreased in rats with inflammation. Also, expression of CD45RC in CD4+ T-cells was twice as high in prostate glands (but three times lower in spleens) in rats with prostate inflammation. Because this technique for inducing inflammation doesn’t provoke a whole-body immune response, it could be a good way to study the immunological aspects of prostatitis, the researchers said. They also hypothesized that an imbalance between the CD4+CD45RC+ T-subset, which can start a cell-mediated immune response, and the CD4+CD161a+ NKT-cells, which are known to suppress autoimmunity, may play a role in the development of spontaneous prostate inflammation.
CLINICAL SIGNIFICANCE OF ANTI-MICROBIAL THERAPY IN CHRONIC PROSTATITIS ASSOCIATED WITH NON-TRADITIONAL UROPATHOGENS
J. Curtis Nickel, Kingston, ON, Canada; Neringa Zadeikis, Michael Spivey, Shu-Chen Wu, Raritan, NJ
It isn’t clear what it means when urologists find bacteria associated with the prostate that aren’t ones traditionally thought to cause urinary tract infections in men with chronic bacterial prostatitis. To find out whether these bacteria are significant, these researchers looked at the changes in the traditional and nontraditional bacteria before and after men were treated with the antibiotics levofloxacin or ciprofloxacin in a randomized, double-blind trial. Of 261 men, 136 (52%) had traditional uropathogens (Escherichia coli, Enterococcus faecalis), and 125 (48%) had nontraditional bacteria (coagulase-negative Staphylococcus and Streptococcus) at the test-of-cure visit (5 to 12 days after end of therapy). Bacterial eradication rates were similar in the two groups (74.3% in those with traditional uropathogens and 77.6% in those with nontraditional bacteria). The success of antibiotic treatment was also similar in the two groups, 76.5% and 71.2%, respectively. In both groups, symptom improvement correlated significantly with bacterial eradication. There were no differences between the antibiotics in how well they eradicated bacteria or reduced symptoms. This study supports the theory that bacteria not traditionally thought of as uropathogens are important in causing chronic bacterial prostatitis, and men who show these bacteria in EPS and VB3 specimens and have symptoms need to be treated.
CLINICAL OUTCOME OF ACUTE PROSTATITIS, A MULTICENTER STUDY
In Rae Cho, K. S. Lee, J. S. Jeon, S. S. Park, L. C. Sung, Choong Hee Noh, Koyang/ Kyunggido, Republic of Korea; Won Jae Yang, Young Deuk Choi, S. J. Hong, Seung Choul Yang, Seoul, Republic of Korea; Jin Seon Cho, Anyang/ Kyunggido, Republic of Korea; H. S. Ahn, Se Joong Kim, Suwon/ Kyunggido, Republic of Korea; Hong Sup Kim, Chungju, Republic of Korea; K. Song, Daejoun, Republic of Korea; D. H. Seong, Jun Kyu Suh, Incheon, Republic of Korea; K. S. Lee, Kyungju, Republic of Korea; Dong H. Lee, Yun Seob Song, Seoul, Republic of Korea; Y. S. Kim, Koyang/ Kyunggido, Republic of Korea
This retrospective analysis of patient records from 11 South Korean hospitals shows how acute prostatitis is typically diagnosed and treated in that country. The most common chief complaint was high fever, and the most common causative organism was Escherichia coli. The patients’ mean age was 54.9 years, and the mean hospital stay was 7.5 days, with a maximum of 3 weeks. PSA was elevated in 78% of patients. Intravenous antibiotic therapy included cephalosporin, aminoglycoside, and quinolone antibiotics. Alpha blockers were added in 54% of cases. Oral quinolone and celpahlosporin antibiotics and alpha blockers were prescribed for a mean of 4.9 weeks after discharge, with 21% of patients taking medication for 8 weeks and 8% for 12 weeks. Chronic prostatitis findings were noted in 5% to 8% of patients.