Prostatitis Category III: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Category III: CP/CPPS

Signs and Symptoms

In chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) there is pelvic pain of unknown cause, lasting longer than 3 months,[1] as the key symptom. Symptoms may wax and wane. Pain can range from mild discomfort to debilitating. Pain may radiate to back and rectum, making sitting difficult. Dysuria, arthralgia, myalgia, unexplained fatigue, abdominal pain, constant burning pain in the penis, and frequency may all be present. Frequent urination and increased urgency may suggest interstitial cystitis (inflammation centred in bladder rather than prostate). Ejaculation may be painful, as the prostate contracts during emission of semen, although nerve- and muscle-mediated post-ejaculatory pain is more common, and a classic sign of CP/CPPS. Some patients report low libido, sexual dysfunction and erectile difficulties. Pain after ejaculation is a very specific complaint that distinguishes CP/CPPS from men with BPH or normal men.

Theories of Etiology

Theories behind the disease include autoimmunity, for which there is scant evidence, neurogenic inflammation and myofascial pain syndrome. In the latter two categories, dysregulation of the local nervous system due to past trauma, infection or an anxious disposition and chronic albeit unconscious pelvic tensing lead to inflammation that is mediated by substances released by nerve cells (such as substance P). The prostate (and other areas of the genitourinary tract: bladder, urethra, testicles) can become inflamed by the action of the chronically activated pelvic nerves on the mast cells at the end of the nerve pathways. Similar stress-induced genitourinary inflammation has been shown experimentally in other mammals.[2] However, there is no correlation between inflammation on histological examination of the prostate and the National Institutes of Health Chronic Prostatitis Symptom Index.[3]

The bacterial infection theory that for so long had held sway in this field was shown to be unimportant in a 2003 study from the University of Washington team led by Dr Lee and Professor Richard Berger. The study found that one third of both normal men and patients had equal counts of similar bacteria colonizing their prostates.[4] This view was endorsed by Dr Anthony Schaeffer, Professor and Chairman of the Department of Urology at Feinberg School of Medicine, in a 2003 editorial of The Journal of Urology, in which he stated that "these data suggest that bacteria do not have a significant role in the development of the chronic pelvic pain syndrome",[5] and a year later with his colleagues he published studies showing that antibiotics are essentially useless for CP/CPPS.[6][7] Since the publication of these studies, the focus has shifted from infection to neuromuscular and psychological etiologies for chronic prostatitis (CP/CPPS); a 2005 study showed that stress is correlated to cat III prostatitis.[8]

Additional theories and observations include:

Possible Role of Unculturable Bacteria in CPPS

A 2007 Croatian study, without controls, suggested that prostatitis syndrome patients may be infected with a wide variety of microbes. The study used McCoy culture and Lugol stain or by immunofluorescent typing with monoclonal antibodies to come to these findings.[9] If this study refers to men with CPPS, it is not in line with major studies from other centres.[4][10]

CPPS as a Form of Interstitial Cystitis

Some researchers have suggested that CPPS is a form of interstitial cystitis. A large multicenter prospective randomized controlled study showed that Elmiron was slightly better than placebo in treating the symptoms of CPPS, however the primary endpoint did not reach statistical significance.[11] Other therapies shown more effective than Elmiron in treating interstitial cystitis, such as quercetin and Elavil (amitriptyline), can help with chronic prostatitis.

Effect of Cold Exposure

Studies in 2007 showed that CPPS is associated with cold weather and exposure to cold.[12][13]

Diagnosis

There are no definitive diagnostic tests for CP/CPPS. This is a poorly understood disorder, even though it accounts for 90%-95% of prostatitis diagnoses.[14] It is found in men of any age, with the peak onset in the early 30s. CP/CPPS may be inflammatory (category IIIa) or non-inflammatory (category IIIb). In the inflammatory form, urine, semen, and other fluids from the prostate contain pus cells (dead white blood cells or WBCs), whereas in the non-inflammatory form no pus cells are present. Recent studies have questioned the distinction between categories IIIa and IIIb, since both categories show evidence of inflammation if pus cells are ignored and other more subtle signs of inflammation, like cytokines, are measured. In 2006, Chinese researchers found that men with categories IIIa and IIIb both had significantly and similarly raised levels of anti-inflammatory cytokine TGFß1 and pro-inflammatory cytokine IFN-γ in their expressed prostatic secretions when compared with controls; therefore measurement of these cytokines could be used to diagnose category III prostatitis.[15]

Normal men have slightly more bacteria in their semen than men with CPPS.[10] The traditional Stamey 4-glass test is invalid for diagnosis of this disorder, and inflammation cannot be localized to any particular area of the lower GU tract.

Men with CP/CPPS are more likely than the general population to suffer from chronic fatigue syndrome (CFS),[16] and irritable bowel syndrome (IBS). Prostate specific antigen levels may be elevated, although there is no malignancy.

Experimental tests that could be useful in the future include tests to measure semen and prostate fluid cytokine levels. Various studies have shown increases in markers for inflammation such as elevated levels of cytokines, myeloperoxidase, and chemokines.

Treatment

A 2007 review article by Dr Potts and Payne in the Cleveland Clinic Journal of Medicine states:[17]

"Indeed, chronic abacterial prostatitis (also known as chronic pelvic pain syndrome) is both the most prevalent form and also the least understood and the most challenging to evaluate and treat. This form of prostatitis may respond to non-prostate-centered treatment strategies such as physical therapy, myofascial trigger point release, and relaxation techniques."

Physical and Psychological Therapy

For chronic nonbacterial prostatitis (Cat III), also known as CP/CPPS, which makes up the majority of men diagnosed with prostatitis, a treatment called the Stanford Protocol,[18] developed by Stanford University School of Medicine Professor of Urology Rodney Anderson and psychologist David Wise in 1996, has recently been published. This is a combination of medication (using tricyclic antidepressants and benzodiazepines), psychological therapy (paradoxical relaxation, an advancement and adaptation, specifically for pelvic pain, of a type of progressive relaxation technique developed by Edmund Jacobson during the early 20th century), and physical therapy (trigger point release therapy on pelvic floor and abdominal muscles, and also yoga-type exercises with the aim of relaxing pelvic floor and abdominal muscles).[19] [20] While these studies are encouraging, definitive proof of efficacy would require a randomized, sham controlled, blinded study, which is not as easy to do with physical therapy as with drug therapy.

Cat. III prostatitis may have no initial trigger other than anxiety, often with an element of Obsessive Compulsive Disorder or other anxiety-spectrum problem. This is theorized to leave the pelvic area in a sensitized condition resulting in a loop of muscle tension and heightened neurological feedback (neural wind-up). Current protocols largely focus on stretches to release overtensed muscles in the pelvic or anal area (commonly referred to as trigger points), physical therapy to the area, and progressive relaxation therapy to reduce causative stress. Biofeedback physical therapy to relearn how to control pelvic floor muscles may be useful.[21]

Aerobic exercise can help those sufferers who are not also suffering from chronic fatigue syndrome (CFS) or whose symptoms are not exacerbated by exercise.[22]

Food Allergies

Anecdotal evidence suggests that food allergies and intolerances may have a role in exacerbating CP/CPPS, perhaps through mast cell mediated mechanisms. Specifically patients with gluten intolerance or celiac disease report severe symptom flares after sustained gluten ingestion. Patients may therefore find an exclusion diet helpful in lessening symptoms by identifying problem foods. Studies are lacking in this area.

Pharmacological Treatment

There is a substantial list of medications used to treat this disorder.[23]

  • Alpha blockers (tamsulosin, alfuzosin) are moderately helpful for many men with CPPS;[24] duration of therapy needs to be at least 3 months.[25]
  • Quercetin has shown effective in a randomized, placebo-controlled trial in chronic prostatitis using 500 mg twice a day for 4 weeks.[26] Subsequent studies showed that quercetin, a mast cell inhibitor, reduces inflammation and oxidative stress in the prostate.
  • Pollen extract (Cernilton) has also been shown effective in randomized placebo controlled trials.[27][28][29]
  • Commonly used therapies that have not been properly evaluated in clinical trials are dietary modification, gabapentin, and amitriptyline.
  • Therapies shown to be ineffective by randomized placebo/sham controlled trials: levaquin (antibiotics), alpha blockers for 6 weeks or less, transurethral needle ablation of the prostate (TUNA).
  • At least one study suggests that multi-modal therapy (aimed at different pathways such as inflammation and neuromuscular dysfunction simultaneously) is better long term than monotherapy.[30]

Prognosis

In recent years the prognosis for CP/CPPS has improved greatly with the advent of multimodal treatment, phytotherapy and protocols aimed at quieting the pelvic nerves through myofascial trigger point release and anxiety control.

References

  1. Luzzi, GA. (2002). "Chronic prostatitis and chronic pelvic pain in men: aetiology, diagnosis and management". J Eur Acad Dermatol Venereol. 16 (3): 253-256.
  2. Alexacos N, Pang X, Boucher W, Cochrane DE, Sant GR, Theoharides TC (1999). "Neurotensin mediates rat bladder mast cell degranulation triggered by acute psychological stress". Urology. 53 (5): 1035–40. PMID 10223502.
  3. Nickel JC, Roehrborn CG, O'leary MP, Bostwick DG, Somerville MC, Rittmaster RS (2007). "Examination of the relationship between symptoms of prostatitis and histological inflammation: baseline data from the REDUCE chemoprevention trial". J. Urol. 178 (3 Pt 1): 896–900, discussion 900–1. doi:10.1016/j.juro.2007.05.041. PMID 17632164.
  4. 4.0 4.1 Lee JC, Muller CH, Rothman I; et al. (2003). "Prostate biopsy culture findings of men with chronic pelvic pain syndrome do not differ from those of healthy controls". J. Urol. 169 (2): 584–7, discussion 587–8. doi:10.1097/01.ju.0000045673.02542.7a. PMID 12544312.
  5. Schaeffer AJ (2003). "Editorial: Emerging concepts in the management of prostatitis/chronic pelvic pain syndrome". J Urol. 169 (2): 597-598. PMID 12544315.
  6. Alexander RB, Propert KJ, Schaeffer AJ; et al. (2004). "Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial". Ann. Intern. Med. 141 (8): 581–9. PMID 15492337.
  7. Nickel JC, Downey J, Clark J; et al. (2003). "Levofloxacin for chronic prostatitis/chronic pelvic pain syndrome in men: a randomized placebo-controlled multicenter trial". Urology. 62 (4): 614–7. PMID 14550427.
  8. Ullrich PM, Turner JA, Ciol M, Berger R (2005). "Stress is associated with subsequent pain and disability among men with nonbacterial prostatitis/pelvic pain". Annals of behavioral medicine : a publication of the Society of Behavioral Medicine. 30 (2): 112–8. doi:10.1207/s15324796abm3002_3. PMID 16173907.
  9. Skerk V, Krhen I, Cajić V, Markovinović L, Puntarić A, Roglić S, Zekan S, Ljubin-Sternak S, Zidovec Lepej S, Vince A. (2007). "The Role of Chlamydia trachomatis in Prostatitis Syndrome - Our Experience in Diagnosis and Treatment". Acta Dermatovenerol Croat. 3: 135–140, . PMID 17868538.
  10. 10.0 10.1 Leukocytes and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome compared to asymptomatic controls J Urol. 2003 Sep;170(3):818-22 (Nickel JC, Alexander RB, Schaeffer AJ)
  11. Nickel JC, Forrest JB, Tomera K; et al. (2005). "Pentosan polysulfate sodium therapy for men with chronic pelvic pain syndrome: a multicenter, randomized, placebo controlled study". J. Urol. 173 (4): 1252–5. doi:10.1097/01.ju.0000159198.83103.01. PMID 15758763.
  12. Hedelin H, Jonsson K (2007). "Chronic prostatitis/chronic pelvic pain syndrome: Symptoms are aggravated by cold and become less distressing with age and time": 1–5. doi:10.1080/00365590701428517. PMID 17853027.
  13. Hedelin H, Jonsson K (2007). "Chronic abacterial prostatitis and cold exposure": 1–6. doi:10.1080/00365590701365123. PMID 17853032.
  14. Habermacher GM, Chason JT, Schaeffer AJ. (2006). "Prostatitis/chronic pelvic pain syndrome". Annu Rev Med. 57: 195-206.
  15. Ding XG, Li SW, Zheng XM, Hu LQ. (2006). "[IFN-gamma and TGF-beta1, levels in the expressed prostatic secretions of patients with chronic abacterial prostatitis]". Zhonghua Nan Ke Xue. 12 (11): 982-984.
  16. Leslie A Aaron; et al. (2001). "Comorbid Clinical Conditions in Chronic Fatigue, A Co-Twin Control Study". J Gen Intern Med. 16 (1): 24-31.
  17. Potts J, Payne RE (2007 May). "Prostatitis: Infection, neuromuscular disorder, or pain syndrome? Proper patient classification is key". Cleve Clin J Med. 74 (Suppl 3): S63-71. Check date values in: |year= (help)
  18. "The Stanford Protocol" (html). 2005. Retrieved 2006-12-09.
  19. Trigger Points and Relaxation in the Treatment of Prostatitis J Urol. 2005 Jul;174(1):155-60 (Anderson RU, Wise D, Sawyer T, Chan C.)
  20. Sexual Dysfunction in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Improvement After Trigger Point Release and Paradoxical Relaxation Training J Urol. 2006 Oct;176(4 Pt 1):1534-8; discussion 1538-9 (Anderson RU, Wise D, Sawyer T, Chan C.)
  21. Cornel EB; et al. (2005). "The effect of biofeedback physical therapy in men with Chronic Pelvic Pain Syndrome Type III". Eur Urol. 47 (5): 607-11.
  22. Giubilei G, Mondaini N, Minervini A, Saieva C, Lapini A, Serni S, Bartoletti R, Carini M. (2007). "Physical Activity of Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome Not Satisfied With Conventional Treatments-Could it Represent a Valid Option? The Physical Activity and Male Pelvic Pain Trial: A Double-Blind, Randomized Study". J Urol. 177 (1): 159-65.
  23. "Pharmacological treatment options for prostatitis/chronic pelvic pain syndrome" (html). 2006. Retrieved 2006-12-11.
  24. "...tamsulosin did not substantially reduce symptoms in men with long-standing CP/CPPS who had at least moderate symptoms." Alexander RB, Propert KJ, Schaeffer AJ, Landis JR, Nickel JC, O'Leary MP, Pontari MA, McNaughton-Collins M, Shoskes DA, Comiter CV, Datta NS, Fowler JE Jr, Nadler RB, Zeitlin SI, Knauss JS, Wang Y, Kusek JW, Nyberg LM Jr, Litwin MS; Chronic Prostatitis Collaborative Research Network. (2004). "Ciprofloxacin or tamsulosin in men with chronic prostatitis/chronic pelvic pain syndrome: a randomized, double-blind trial". Ann Intern Med. 141 (8): 581-9.
  25. "...treatment duration should be long enough (more than 3 months)"Yang G; et al. (2006). "The effect of alpha-adrenergic antagonists in chronic prostatitis/chronic pelvic pain syndrome: a meta-analysis of randomized controlled trials". J Androl. 27 (6): 847-52.
  26. Shoskes, DA; et al. (1999). "Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial". Urology. 54 (6): 960-3.
  27. Suzuki T; et al. (1992). "[Clinical effect of Cernilton in chronic prostatitis]". Hinyokika Kiyo. 38 (4): 489-94.
  28. Yan, H; et al. (2004). "[Efficacy of Prostat in the treatment of NIH category IIIA prostatitis]". Zhonghua Nan Ke Xue. 10 (12): 930-1.
  29. Elist J (2006). "Effects of pollen extract preparation Prostat/Poltit on lower urinary tract symptoms in patients with chronic nonbacterial prostatitis/chronic pelvic pain syndrome: a randomized, double-blind, placebo-controlled study". Urology. 67 (1): 60-3.
  30. Potts JM (2005). "Therapeutic options for chronic prostatitis/chronic pelvic pain syndrome". Curr Urol Rep. 6 (4): 313-7.

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