Chronic prostatitis/chronic pelvic pain syndrome
|Chronic nonbacterial prostatitis|
|Classification and external resources|
Chronic nonbacterial prostatitis or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a pelvic pain condition in men, and should be distinguished from other forms of prostatitis such as chronic bacterial prostatitis and acute bacterial prostatitis. This condition was formerly known as prostatodynia (painful prostate). CP/CPPS and interstitial cystitis are sometimes referred to jointly as "UCPPS" (urologic chronic pelvic pain syndrome).
- 1 Signs and symptoms
- 2 Cause
- 3 Diagnosis
- 4 Treatment
- 5 Epidemiology
- 6 Prognosis
- 7 Research
- 8 Society and culture
- 9 References
- 10 External links
Signs and symptoms
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pelvic or perineal pain without evidence of urinary tract infection, lasting longer than 3 months, as the key symptom. Symptoms may wax and wane. Pain can range from mild to debilitating. Pain may radiate to the back and rectum, making sitting uncomfortable. Pain can be present in the perineum, testicles, tip of penis, pubic or bladder area. 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). Post-ejaculatory pain, mediated by nerves and muscles, is a hallmark of the condition, and serves to distinguish CP/CPPS patients from men with BPH or normal men. Some patients report low libido, sexual dysfunction and erectile difficulties.
A 2016 review paper found that although the peripheral nervous system is responsible for starting the condition, the central nervous system (CNS) is responsible for continuing the pain even without continuing input from the peripheral nerves.
Nerves, stress and hormones
The symptoms of CP/CPPS appear to result from an interplay between psychological factors and dysfunction in the immune, neurological and endocrine systems.
Theories behind the disease include stress-driven hypothalamic-pituitary-adrenal axis dysfunction and adrenocortical hormone (endocrine) abnormalities, 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. However, there is no correlation between inflammation on histological examination of the prostate and the National Institutes of Health Chronic Prostatitis Symptom Index.
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. This view was endorsed by Dr Anthony Schaeffer, Professor and Chairman of the Department of Urology at Northwestern University, 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", and a year later with his colleagues he published studies showing that antibiotics are essentially useless for CP/CPPS. Since the publication of these studies, the research focus has shifted from infection to neuromuscular, behavioral, psychological, and genetic cause for UCPPS (CP/CPPS and IC/PBS), where the interplay between the lower urinary tract and other physiological systems is stressed. UCPPS is now studied as a systemic disorder. In support of this approach, a 2005 study showed that stress is correlated to Cat III prostatitis.
Overlap with BPS/IC
Some researchers have suggested that CPPS is a form of bladder pain syndrome/interstitial cystitis (BPS/IC). In 2007 the NIDDK began to group IC/PBS and CP/CPPS under the umbrella term Urologic Chronic Pelvic Pain Syndromes (UCPPS). Therapies shown to be effective in treating IC/PBS, such as quercetin, have also shown some efficacy in CP/CPPS. Recent research has focused on genomic and proteomic aspects of the related conditions.
Patients may experience pain with bladder filling, which is also a typical sign of IC.
The ambient temperature appears to play a role as cold is frequently reported as causing symptom aggravation and heat is often reported to be ameliorating. It appears that cold is one of the factors that can trigger a process resulting in CP/CPPS. Cold also causes aggravation of symptoms and can initiate a relapse. A survey showed that the occurrence of prostatitis symptoms in men living in northern Finland —a cold climate—is higher than that reported in other parts of the world. This could be partly caused by the cold climate.
Anecdotal evidence suggests that food allergies and intolerances may have a role in exacerbating CP/CPPS, perhaps through mast cell mediated mechanisms. There is also some evidence of an association between urologic pain syndromes, such as IC/BPS and CP/CPPS, with non-celiac gluten sensitivity in some patients. Patients may therefore find an elimination diet helpful in lessening symptoms by identifying problem foods. Studies are lacking in this area.
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. It is found in men of any age, with the peak incidence in men aged 35–45 years. CP/CPPS may be inflammatory (Category Ⅲa) or non-inflammatory (Category Ⅲb), based on levels of pus cells in expressed prostatic secretions (EPS), but these subcategories are of limited use clinically. 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 TGFβ1 and pro-inflammatory cytokine IFN-γ in their EPS when compared with controls; therefore measurement of these cytokines could be used to diagnose category Ⅲ prostatitis. A 2010 study found that nerve growth factor could also be used as a biomarker of the condition.
For CP/CPPS patients, analysis of urine and expressed prostatic secretions for leukocytes is debatable, especially due to the fact that the differentiation between patients with inflammatory and non-inflammatory subgroups of CP/CPPS is not useful. Serum PSA tests, routine imaging of the prostate, and tests for Chlamydia trachomatis and Ureaplasma provide no benefit for the patient.
Extraprostatic abdominal/pelvic tenderness is present in >50% of patients with chronic pelvic pain syndrome but only 7% of controls. Healthy men have slightly more bacteria in their semen than men with CPPS. The high prevalence of WBCs and positive bacterial cultures in the asymptomatic control population raises questions about the clinical usefulness of the standard 4-glass test as a diagnostic tool in men with CP/CPPS. The use of the four-glass test by American urologists is now rare, with only 4% using it regularly.
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.
Some conditions have similar symptoms to chronic prostatitis: Bladder neck hypertrophy and urethral stricture may both cause similar symptoms through urinary reflux (inter alia), and can be excluded through flexible cytoscopy and urodynamic tests.
A distinction is sometimes made between "IIIa" (Inflammatory) and "IIIb" (Noninflammatory) forms of CP/CPPS, depending on whether pus cells (WBCs) can be found in the expressed prostatic secretions (EPS) of the patient. Some researchers have questioned the usefulness of this categorisation, calling for the Meares–Stamey four-glass test to be abandoned.
In 2007, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) began using the umbrella term Urologic Chronic Pelvic Pain Syndromes (UCPPS), for research purposes, to refer to pain syndromes associated with the bladder (i.e. interstitial cystitis/painful bladder syndrome, IC/PBS) and the prostate gland (i.e. chronic prostatitis/chronic pelvic pain syndrome, CP/CPPS).
Older terms for this condition are "prostatodynia" (prostate pain) and non-bacterial chronic prostatitis.
UPOINT symptom classification
A classification system called "UPOINT" was developed by urologists Shoskes and Nickel to allow clinical profiling of a patient's symptoms into six broad categories:
- Urinary symptoms
- Psychological dysfunction
- Organ-specific symptoms
- Infectious causes
- Neurologic dysfunction
- Tenderness of the pelvic floor muscles
The UPOINT system allows for individualized and multimodal therapy.
Chronic pelvic pain syndrome is difficult to treat.
Category III prostatitis may have no initial trigger other than anxiety, often with an element of OCD, panic 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 pain wind-up). Current protocols largely focus on stretches to release overtensed muscles in the pelvic or anal area (commonly referred to as trigger points) including digital intrarectal massage, physical therapy to the area, and progressive relaxation therapy to reduce causative stress.
Aerobic exercise can help those sufferers who are not also suffering from chronic fatigue syndrome or whose symptoms are not exacerbated by exercise. Acupuncture has reportedly benefited some patients.
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 Wise–Anderson Protocol (aka the "Stanford Protocol"), 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)
- 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).
Biofeedback physical therapy to relearn how to control pelvic floor muscles may be useful. Biofeedback is satisfactory for treatment of chronic prostatitis (with mainly voiding problems) during puberty.
- Treatment with antibiotics is controversial. Some have found benefits in symptoms while others have questioned the utility of a trial of antibiotics. Antibiotics are known to have anti-inflammatory properties and this has been suggested as an explanation for their partial efficacy in treating CPPS. Antibiotics such as quinolones, tetracyclines and macrolides have direct anti-inflammatory properties in the absence of infection, blocking cytokines such as interleukin-1 (IL-1), interleukin-8 and tumor necrosis factor (TNF), which coincidentally are the same cytokines found to be elevated in the semen and EPS of men with chronic prostatitis.
- The effectiveness of alpha blockers (tamsulosin, alfuzosin) is questionable in men with CPPS. A 2006 meta analysis found that they are moderately beneficial when the duration of therapy was at least 3 months.
- An estrogen reabsorption inhibitor such as mepartricin improves voiding, reduces urological pain and improves quality of life in patients with chronic non-bacterial prostatitis.
- Therapies that have not been properly evaluated in clinical trials although there is supportive anecdotal evidence include: gabapentin, benzodiazepines and amitriptyline.
The annual prevalence in the general population of chronic pelvic pain syndrome is 0.5%. 38% of primary care providers, when presented with a vignette of a man with CPPS, indicate that they have never seen such a patient. However, the overall prevalence of symptoms suggestive of CP/CPPS is 6.3%. The role of the prostate was questioned in the cause of CP/CPPS when both men and women in the general population were tested using the (1) National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) —with the female homolog of each male anatomical term use on questionnaires for female participants— (2) the International Prostate Symptom Score (IPSS), and (3) additional questions on pelvic pain. The prevalence of symptoms suggestive of CPPS in this selected population was 5.7% in women and 2.7% in men, placing in doubt the role of the prostate gland. New evidence suggests that the prevalence of CP/CPPS is much higher in teenage males than once suspected.
In recent years the prognosis for CP/CPPS has improved with the advent of multimodal treatment, phytotherapy, protocols aimed at quieting the pelvic nerves through myofascial trigger point release and anxiety control, and chronic pain therapy.
In a preliminary 2005 open label study of 16 treatment-recalcitrant CPPS patients, controversial entities known as nanobacteria were proposed as a cause of prostatic calcification and symptoms found in CPPS. Patients were treated with EDTA (to dissolve the calcifications) and 3 months of tetracycline (a calcium-leaching antibiotic with anti-inflammatory effects, used here to kill the "pathogens"), and half had significant improvement in symptoms. Scientists have expressed strong doubts about whether nanobacteria are living organisms. Research in 2008 showed that "nanobacteria" are merely tiny lumps of abiotic limestone.
The evidence supporting a viral cause of prostatitis and chronic pelvic pain syndrome is weak. Single case reports have implicated herpes simplex virus (HSV) and cytomegalovirus (CMV) but a study using PCR failed to demonstrate the presence of viral DNA in patients with chronic pelvic pain syndrome undergoing radical prostatectomy for localized prostate cancer. The reports implicating CMV must be interpreted with caution because in all cases the patients were immunocompromised. For HSV the evidence is weaker still and there is only one reported case and the causative role of the virus was not proven, and there are no reports of successful treatments using antiviral drugs such as aciclovir.
Due to the concomitant presence of bladder disorders, gastrointestinal disorders, and mood disorders, research has been conducted to understand whether CP/CPPS might be caused by problems with the hypothetical bladder-gut-brain axis.
Research has been conducted to understand how chronic bladder pain affects the brain, using techniques like MRI and functional MRI; as of 2016 it appeared that people with CP/CPPS have increased grey matter in the primary somatosensory cortex, the Insular cortex, the insular cortex, and the anterior cingulate cortex, and in the central nucleus of the amygdala; studies in rodents have shown that blocking the metabotropic glutamate receptor 5 which is expressed in the central nucleus of the amygdala, can block bladder pain.
Society and culture
Notable cases have included:
- John Anderson— Deputy Prime Minister of Australia
- James Boswell—author of Life of Samuel Johnson
- John Cleese—British actor
- Vincent Gallo—movie director
- Glenn Gould—pianist
- John F Kennedy— President of the United States of America
- Tim Parks—British novelist, translator and author.
- Howard Stern— radio personality
- William Styron—author (Sophie's Choice)
- Schaeffer, A. J.; Datta, N. S.; Fowler Jr, J. E.; Krieger, J. N.; Litwin, M. S.; Nadler, R. B.; Nickel, J. C.; Pontari, M. A.; Shoskes, D. A.; Zeitlin, S. I.; Hart, C.; Chronic Prostatitis Collaborative Research Network (2002). "Overview summary statement. Diagnosis and management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)". Urology. 60 (6 Suppl): 1–4. doi:10.1016/S0090-4295(02)01979-9. PMID 12521576.
- Holt JD, Garrett WA, McCurry TK, Teichman JM (2016). "Common Questions About Chronic Prostatitis". Am Fam Physician. 93 (4): 290–6. PMID 26926816.
- Schaeffer AJ (2007). "Epidemiology and evaluation of chronic pelvic pain syndrome in men". Int J Antimicrob Agents. 31: S108–11. doi:10.1016/j.ijantimicag.2007.08.027. PMID 18164597.
- Luzzi GA (2002). "Chronic prostatitis and chronic pelvic pain in men: aetiology, diagnosis and management". Journal of the European Academy of Dermatology and Venereology : JEADV. 16 (3): 253–6. doi:10.1046/j.1468-3083.2002.00481.x. PMID 12195565.
- Clemens, J Quentin; Meenan, Richard T; O'Keeffe Rosetti, Maureen C; Gao, Sara Y; Calhoun, Elizabeth A (Dec 2005). "Incidence and clinical characteristics of National Institutes of Health type III prostatitis in the community". J Urol. 174 (6): 2319–22. doi:10.1097/01.ju.0000182152.28519.e7. PMID 16280832.
- Shoskes DA, Landis JR, Wang Y, Nickel JC, Zeitlin SI, Nadler R; Landis; Wang; Nickel; Zeitlin; Nadler; Chronic Prostatitis Collaborative Research Network Study Group (August 2004). "Impact of post-ejaculatory pain in men with category III chronic prostatitis/chronic pelvic pain syndrome". J. Urol. 172 (2): 542–7. doi:10.1097/01.ju.0000132798.48067.23. PMID 15247725.
- Sadler, KE; Kolber, BJ (July 2016). "Urine Trouble: Alterations in Brain Function Associated with Bladder Pain". The Journal of Urology. 196 (1): 24–32. doi:10.1016/j.juro.2015.10.198. PMC . PMID 26905019.
- Pontari MA, Ruggieri MR; Ruggieri (May 2008). "Mechanisms in prostatitis/chronic pelvic pain syndrome". J. Urol. 179 (5 Suppl): S61–7. doi:10.1016/j.juro.2008.03.139. PMID 18405756.
- Anderson RU, Orenberg EK, Chan CA, Morey A, Flores V; Orenberg; Chan; Morey; Flores (2008). "Psychometric Profiles and Hypothalamic-Pituitary-Adrenal Axis Function in Men With Chronic Prostatitis/Chronic Pelvic Pain Syndrome". J Urol. 179 (3): 956–60. doi:10.1016/j.juro.2007.10.084. PMC . PMID 18207189.
- Dimitrakov J, Joffe HV, Soldin SJ, Bolus R, Buffington CA, Nickel JC; Joffe; Soldin; Bolus; Buffington; Nickel (2008). "Adrenocortical Hormone Abnormalities in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome". Urology. 71 (2): 261–266. doi:10.1016/j.urology.2007.09.025. PMC . PMID 18308097.
- Theoharides TC, Cochrane DE; Cochrane (2004). "Critical role of mast cells in inflammatory diseases and the effect of acute stress". J. Neuroimmunol. 146 (1–2): 1–12. doi:10.1016/j.jneuroim.2003.10.041. PMID 14698841.
- Theoharides TC, Kalogeromitros D; Kalogeromitros (2006). "The critical role of mast cells in allergy and inflammation". Ann. N. Y. Acad. Sci. 1088: 78–99. Bibcode:2006NYASA1088...78T. doi:10.1196/annals.1366.025. PMID 17192558.
- Sant GR, Kempuraj D, Marchand JE, Theoharides TC; Kempuraj; Marchand; Theoharides (2007). "The mast cell in interstitial cystitis: role in pathophysiology and pathogenesis". Urology. 69 (4 Suppl): 34–40. doi:10.1016/j.urology.2006.08.1109. PMID 17462477.
- Anderson RU, Wise D, Sawyer T, Chan C; Wise; Sawyer; Chan (2005). "Integration of myofascial trigger point release and paradoxical relaxation training treatment of chronic pelvic pain in men". J. Urol. 174 (1): 155–60. doi:10.1097/01.ju.0000161609.31185.d5. PMID 15947608.
- Anderson RU, Wise D, Sawyer T, Chan CA; Wise; Sawyer; Chan (2006). "Sexual dysfunction in men with chronic prostatitis/chronic pelvic pain syndrome: improvement after trigger point release and paradoxical relaxation training". J. Urol. 176 (4 Pt 1): 1534–8; discussion 1538–9. doi:10.1016/j.juro.2006.06.010. PMID 16952676.
- Alexacos N, Pang X, Boucher W, Cochrane DE, Sant GR, Theoharides TC; Pang; Boucher; Cochrane; Sant; Theoharides (1999). "Neurotensin mediates rat bladder mast cell degranulation triggered by acute psychological stress". Urology. 53 (5): 1035–40. doi:10.1016/S0090-4295(98)00627-X. PMID 10223502.
- Nickel JC, Roehrborn CG, O'leary MP, Bostwick DG, Somerville MC, Rittmaster RS; Roehrborn; O'Leary; Bostwick; Somerville; Rittmaster (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.
- Lee JC; Muller CH; Rothman I; et al. (February 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 (inactive 2017-01-16). PMID 12544312.
- Schaeffer AJ (2003). "Editorial: Emerging concepts in the management of prostatitis/chronic pelvic pain syndrome". J. Urol. 169 (2): 597–598. doi:10.1016/S0022-5347(05)63961-4. PMID 12544315.
- 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. doi:10.7326/0003-4819-141-8-200410190-00005. PMID 15492337.
- 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. doi:10.1016/S0090-4295(03)00583-1. PMID 14550427.
- "Multi-disciplinary Approach to the Study of Chronic Pelvic Pain". NIDDK—Department of Health and Human Services. 2007. Retrieved 2008-02-12.
- Ullrich PM, Turner JA, Ciol M, Berger R; Turner; Ciol; Berger (2005). "Stress is associated with subsequent pain and disability among men with nonbacterial prostatitis/pelvic pain". Annals of Behavioral Medicine. 30 (2): 112–8. doi:10.1207/s15324796abm3002_3. PMID 16173907.
- Theoharides, TC.; Whitmore, K.; Stanford, E.; Moldwin, R.; O'Leary, MP. (Dec 2008). "Interstitial cystitis: bladder pain and beyond". Expert Opin Pharmacother. 9 (17): 2979–94. doi:10.1517/14656560802519845. PMID 19006474.
- Murphy, AB.; Macejko, A.; Taylor, A.; Nadler, RB. (2009). "Chronic prostatitis: management strategies". Drugs. 69 (1): 71–84. doi:10.2165/00003495-200969010-00005. PMID 19192937.
- Dimitrakov, J.; Dimitrakova, E. (2009). "Urologic chronic pelvic pain syndrome—looking back and looking forward". Folia Med (Plovdiv). 51 (3): 42–4. PMID 19957562.
- Rourke W, Khan SA, Ahmed K, Masood S, Dasgupta P, Khan MS; Khan; Ahmed; Masood; Dasgupta; Khan (June 2014). "Painful bladder syndrome/interstitial cystitis: aetiology, evaluation and management". Arch Ital Urol Androl. 86 (2): 126–31. doi:10.4081/aiua.2014.2.126. PMID 25017594.
- Hedelin H, Jonsson K; Jonsson (2007). "Chronic prostatitis/chronic pelvic pain syndrome: symptoms are aggravated by cold and become less distressing with age and time". Scand. J. Urol. Nephrol. 41 (6): 516–20. doi:10.1080/00365590701428517. PMID 17853027.
- Hedelin H, Jonsson K; Jonsson (2007). "Chronic abacterial prostatitis and cold exposure: an explorative study". Scand. J. Urol. Nephrol. 41 (5): 430–5. doi:10.1080/00365590701365123. PMID 17853032.
- Gao DJ, Guo YS, Yu HY, Wang YJ, Cui WG; Guo; Yu; Wang; Cui (December 2007). "[Prevalence and related factors of prostatitis-like symptoms in young men]". Zhonghua Nan Ke Xue (in Chinese). 13 (12): 1087–90. PMID 18284056.
- Mehik A, Hellström P, Lukkarinen O, Sarpola A, Järvelin M; Hellström; Lukkarinen; Sarpola; Järvelin (September 2000). "Epidemiology of prostatitis in Finnish men: a population-based cross-sectional study". BJU Int. 86 (4): 443–8. doi:10.1046/j.1464-410X.2000.00836.x. PMID 10971269.
- Catassi C (2015). "Gluten Sensitivity". Ann Nutr Metab (Review). 67 Suppl 2 (2): 16–26. doi:10.1159/000440990. PMID 26605537.
- Rostami K, Hogg-Kollars S (2012). "A Patient's Journey. Non-coeliac gluten sensitivity". BMJ. 345: e7982. doi:10.1136/bmj.e7982. PMID 23204003.
- "Gluten and CP/CPPS". Prostatitis Network. Retrieved 2016-03-16.
- Habermacher GM, Chason JT, Schaeffer AJ; Chason; Schaeffer (2006). "Prostatitis/chronic pelvic pain syndrome". Annu. Rev. Med. 57: 195–206. doi:10.1146/annurev.med.57.011205.135654. PMID 16409145.
- Daniel Shoskes (2008). Chronic Prostatitis/Chronic Pelvic Pain Syndrome. Humana Press. p. 171. ISBN 1-934115-27-4.
- A Pontari, M. (Dec 2002). "Inflammation and anti-inflammatory therapy in chronic prostatitis". Urology. 60 (6 Suppl): 29–33; discussion 33–4. doi:10.1016/S0090-4295(02)02381-6. PMID 12521589.
- Ding XG, Li SW, Zheng XM, Hu LQ; Li; Zheng; Hu (2006). "[IFN-gamma and TGF-beta1, levels in the EPS of patients with chronic abacterial prostatitis]". Zhonghua Nan Ke Xue (in Chinese). 12 (11): 982–4. PMID 17146921.
- Watanabe, T.; Inoue, M.; Sasaki, K.; Araki, M.; Uehara, S.; Monden, K.; Saika, T.; Nasu, Y.; Kumon, H.; Chancellor, Michael B. (Sep 2010). "Nerve growth factor level in the prostatic fluid of patients with chronic prostatitis/chronic pelvic pain syndrome is correlated with symptom severity and response to treatment". BJU Int. 108 (2): 248–51. doi:10.1111/j.1464-410X.2010.09716.x. PMID 20883485.
- Weidner W, Anderson RU; Anderson (2007). "Evaluation of acute and chronic bacterial prostatitis and diagnostic management of chronic prostatitis/chronic pelvic pain syndrome with special reference to infection/inflammation". Int J Antimicrob Agents. 31 (2): S91–5. doi:10.1016/j.ijantimicag.2007.07.044. PMID 18162376.
- Shoskes DA, Berger R, Elmi A, Landis JR, Propert KJ, Zeitlin S; Berger; Elmi; Landis; Propert; Zeitlin; Chronic Prostatitis Collaborative Research Network Study Group (2008). "Muscle tenderness in men with chronic prostatitis/chronic pelvic pain syndrome: the chronic prostatitis cohort study". J. Urol. 179 (2): 556–60. doi:10.1016/j.juro.2007.09.088. PMC . PMID 18082223.
- Nickel JC, Alexander RB, Schaeffer AJ, Landis JR, Knauss JS, Propert KJ; Alexander; Schaeffer; Landis; Knauss; Propert; Chronic Prostatitis Collaborative Research Network Study Group (2003). "Leukocytes and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome compared to asymptomatic controls". J. Urol. 170 (3): 818–22. doi:10.1097/01.ju.0000082252.49374.e9. PMID 12913707.
- McNaughton Collins, M.; Fowler, FJ.; Elliott, DB.; Albertsen, PC.; Barry, MJ. (Mar 2000). "Diagnosing and treating chronic prostatitis: do urologists use the four-glass test?". Urology. 55 (3): 403–7. doi:10.1016/S0090-4295(99)00536-1. PMID 10699621.
- 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. doi:10.1111/j.1525-1497.2001.03419.x. PMC . PMID 11251747.
- He, L.; Wang, Y.; Long, Z.; Jiang, C. (Dec 2009). "Clinical Significance of IL-2, IL-10, and TNF-alpha in Prostatic Secretion of Patients With Chronic Prostatitis". Urology. 75 (3): 654–7. doi:10.1016/j.urology.2009.09.061. PMID 19963254.
- Pasqualotto, FF.; Sharma, RK.; Potts, JM.; Nelson, DR.; Thomas, AJ.; Agarwal, A. (Jun 2000). "Seminal oxidative stress in patients with chronic prostatitis". Urology. 55 (6): 881–5. doi:10.1016/S0090-4295(99)00613-5. PMID 10840100.
- Penna, G.; Mondaini, N.; Amuchastegui, S.; Degli Innocenti, S.; Carini, M.; Giubilei, G.; Fibbi, B.; Colli, E.; et al. (Feb 2007). "Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia". Eur Urol. 51 (2): 524–33; discussion 533. doi:10.1016/j.eururo.2006.07.016. PMID 16905241.
- Khadra, A.; Fletcher, P.; Luzzi, G.; Shattock, R.; Hay, P. (May 2006). "Interleukin-8 levels in seminal plasma in chronic prostatitis/chronic pelvic pain syndrome and nonspecific urethritis". BJU Int. 97 (5): 1043–6. doi:10.1111/j.1464-410X.2006.06133.x. PMID 16643489.
- Chiari R (1983). "Urethral obstruction and prostatitis". Int Urol Nephrol. 15 (3): 245–55. doi:10.1007/BF02083011. PMID 6654631.
- Hruz P, Danuser H, Studer UE, Hochreiter WW; Danuser; Studer; Hochreiter (2003). "Non-inflammatory chronic pelvic pain syndrome can be caused by bladder neck hypertrophy". Eur. Urol. 44 (1): 106–10; discussion 110. doi:10.1016/S0302-2838(03)00203-3. PMID 12814683.
- Romero Pérez P, Mira Llinares A; Mira Llinares (1996). "[Complications of the lower urinary tract secondary to urethral stenosis]". Actas Urol Esp (in Spanish). 20 (9): 786–93. PMID 9065088.
- "Prostatitis: Benign Prostate Disease: Merck Manual Professional". Retrieved 2010-04-17.
- "Treatment of Chronic Prostatitis". www.medscape.com. Retrieved 2010-04-18.
- "Multi-disciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network". NIDDK. 2007. Retrieved 2008-01-11.
- Shoskes DA, Nickel JC, Dolinga R, Prots D (2009). "Clinical phenotyping of patients with chronic prostatitis/chronic pelvic pain syndrome and correlation with symptom severity". Urology. 73 (3): 538–42; discussion 542–3. doi:10.1016/j.urology.2008.09.074. PMID 19118880.
- Sandhu J, Tu HV (2017). "Recent advances in managing chronic prostatitis/chronic pelvic pain syndrome". F1000Res. 6. doi:10.12688/f1000research.10558.1. PMC . PMID 29034074.
- Potts J, Payne RE; Payne (May 2007). "Prostatitis: Infection, neuromuscular disorder, or pain syndrome? Proper patient classification is key". Cleveland Clinic journal of medicine. 74 (Suppl 3): S63–71. doi:10.3949/ccjm.74.Suppl_3.S63. PMID 17549825.
- Anderson, RU.; Orenberg, EK.; Morey, A.; Chavez, N.; Chan, CA. (Nov 2009). "Stress induced hypothalamus-pituitary-adrenal axis responses and disturbances in psychological profiles in men with chronic prostatitis/chronic pelvic pain syndrome". J Urol. 182 (5): 2319–24. doi:10.1016/j.juro.2009.07.042. PMID 19762053.
- Li, HC.; Wang, ZL.; Li, HL.; Zhang, N.; Chen, HW.; Zhang, P.; Gan, WM.; Chong, T.; Wang, ZM. (Aug 2008). "[Correlation of the prognosis of chronic prostatitis/chronic pelvic pain syndrome with psychological and other factors: a Cox regression analysis]". Zhonghua Nan Ke Xue. 14 (8): 723–7. PMID 18817346.
- Clemens, JQ.; Brown, SO.; Calhoun, EA. (Oct 2008). "Mental health diagnoses in patients with interstitial cystitis/painful bladder syndrome and chronic prostatitis/chronic pelvic pain syndrome: a case/control study". J Urol. 180 (4): 1378–82. doi:10.1016/j.juro.2008.06.032. PMC . PMID 18707716.
- Giubilei G; Mondaini N; Minervini A; et al. (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. doi:10.1016/j.juro.2006.08.107. PMID 17162029.
- Rosted P (2007). "Chronic prostatitis/chronic pelvic pain syndrome and acupuncture—a case report". Acupunct Med. 25 (4): 198–9. doi:10.1136/aim.25.4.198. PMID 18160930.
- "The Stanford Protocol". 2005. Retrieved 2006-12-09.
- Cornel EB, van Haarst EP, Schaarsberg RW, Geels J; Van Haarst; Schaarsberg; Geels (2005). "The effect of biofeedback physical therapy in men with Chronic Pelvic Pain Syndrome Type III". Eur. Urol. 47 (5): 607–11. doi:10.1016/j.eururo.2004.12.014. PMID 15826751.
- Clemens, J. Q.; Nadler, R. B.; Schaeffer, A. J.; Belani, J.; Albaugh, J.; Bushman, W. (2000). "Biofeedback, pelvic floor re-education, and bladder training for male chronic pelvic pain syndrome". Urology. 56 (6): 951–955. doi:10.1016/S0090-4295(00)00796-2. PMID 11113739.
- Kaplan, S. A.; Santarosa, R. P.; D'alisera, P. M.; Fay, B. J.; Ikeguchi, E. F.; Hendricks, J.; Klein, L.; Te, A. E. (1997). "Pseudodyssynergia (contraction of the external sphincter during voiding) misdiagnosed as chronic nonbacterial prostatitis and the role of biofeedback as a therapeutic option". The Journal of Urology. 157 (6): 2234–2237. doi:10.1016/S0022-5347(01)64727-X. PMID 9146624.
- He, W.; Chen, M.; Zu, X.; Li, Y.; Ning, K.; Qi, L. (2009). "Chronic prostatitis presenting with dysfunctional voiding and effects of pelvic floor biofeedback treatment". BJU international. 105 (7): 975–977. doi:10.1111/j.1464-410X.2009.08850.x. PMID 19751259.
- Li, Y.; Qi, L.; Wen, J.; Zu, X.; Chen, Z. (2006). "Chronic prostatitis during puberty". BJU international. 98 (4): 818–821. doi:10.1111/j.1464-410X.2006.06386.x. PMID 16978277.
- Anothaisintawee, T; Attia, J; Nickel, JC; Thammakraisorn, S; Numthavaj, P; McEvoy, M; Thakkinstian, A (Jan 5, 2011). "Management of chronic prostatitis/chronic pelvic pain syndrome: a systematic review and network meta-analysis". JAMA: the Journal of the American Medical Association. 305 (1): 78–86. doi:10.1001/jama.2010.1913. PMID 21205969.
- Wagenlehner, FM.; Naber, KG.; Bschleipfer, T.; Brähler, E.; Weidner, W. (Mar 2009). "Prostatitis and male pelvic pain syndrome: diagnosis and treatment". Dtsch Arztebl Int. 106 (11): 175–83. doi:10.3238/arztebl.2009.0175 (inactive 2017-01-16). PMC . PMID 19568373.
- Shoskes DA (June 2001). "Use of antibiotics in chronic prostatitis syndromes". Can J Urol. 8 Suppl 1: 24–8. PMID 11442994.
- Yang G, Wei Q, Li H, Yang Y, Zhang S, Dong Q; Wei; Li; Yang; Zhang; Dong (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. doi:10.2164/jandrol.106.000661. PMID 16870951.
...treatment duration should be long enough (more than 3 months)
- Cohen JM, Fagin AP, Hariton E, Niska JR, Pierce MW, Kuriyama A, Whelan JS, Jackson JL, Dimitrakoff JD (2012). "Therapeutic Intervention for Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/ CPPS): A Systematic Review and Meta-Analysis". PLoS ONE. 7 (8): e41941. Bibcode:2012PLoSO...741941C. doi:10.1371/journal.pone.0041941. PMC . PMID 22870266.
- Curtis Nickel, J; Baranowski, AP; Pontari, M; Berger, RE; Tripp, DA (2007). "Management of Men Diagnosed With Chronic Prostatitis/Chronic Pelvic Pain Syndrome Who Have Failed Traditional Management". Reviews in urology. 9 (2): 63–72. PMC . PMID 17592539.
- Leskinen, MJ.; Kilponen, A.; Lukkarinen, O.; Tammela, TL. (Aug 2002). "Transurethral needle ablation for the treatment of chronic pelvic pain syndrome (category III prostatitis): a randomized, sham-controlled study". Urology. 60 (2): 300–4. doi:10.1016/S0090-4295(02)01704-1. PMID 12137830.
- Taylor BC; Noorbaloochi S; McNaughton-Collins M; et al. (May 2008). "Excessive antibiotic use in men with prostatitis". Am. J. Med. 121 (5): 444–9. doi:10.1016/j.amjmed.2008.01.043. PMC . PMID 18456041.
- Phillp Hannno. "Defining The Urologic Chronic Pelvic Pain Syndromes: A New Beginning—An International Symposium". Urotoday. Retrieved 2008-07-22.
- Daniels NA, Link CL, Barry MJ, McKinlay JB; Link; Barry; McKinlay (May 2007). "Association between past urinary tract infections and current symptoms suggestive of chronic prostatitis/chronic pelvic pain syndrome". J Natl Med Assoc. 99 (5): 509–16. PMC . PMID 17534008.
- "NIH CPSI". www.ucpps.org. Retrieved 2009-11-10.
- Marszalek M, Wehrberger C, Temml C, Ponholzer A, Berger I, Madersbacher S; Wehrberger; Temml; Ponholzer; Berger; Madersbacher (April 2008). "Chronic Pelvic Pain and Lower Urinary Tract Symptoms in Both Sexes: Analysis of 2749 Participants of an Urban Health Screening Project". Eur. Urol. 55 (2): 499–507. doi:10.1016/j.eururo.2008.03.073. PMID 18395963.
- Nickel, JC.; Tripp, DA.; Chuai, S.; Litwin, MS.; McNaughton-Collins, M.; Landis, JR.; Alexander, RB.; Schaeffer, AJ.; et al. (Jan 2008). "Psychosocial variables affect the quality of life of men diagnosed with chronic prostatitis/chronic pelvic pain syndrome". BJU Int. 101 (1): 59–64. doi:10.1111/j.1464-410X.2007.07196.x. PMID 17924985.
- Duclos, AJ.; Lee, CT.; Shoskes, DA. (Aug 2007). "Current treatment options in the management of chronic prostatitis". Ther Clin Risk Manag. 3 (4): 507–12. PMC . PMID 18472971.
- Shoskes, DA.; Katz, E. (Jul 2005). "Multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome". Curr Urol Rep. 6 (4): 296–9. doi:10.1007/s11934-005-027-0 (inactive 2017-01-16). PMID 15978233.
- Bergman, J.; Zeitlin, SI. (Mar 2007). "Prostatitis and chronic prostatitis/chronic pelvic pain syndrome". Expert Rev Neurother. 7 (3): 301–7. doi:10.1586/14737126.96.36.1991. PMID 17341178.
- Shoskes DA, Thomas KD, Gomez E; Thomas; Gomez (2005). "Anti-nanobacterial therapy for men with chronic prostatitis/chronic pelvic pain syndrome and prostatic stones: preliminary experience". J. Urol. 173 (2): 474–7. doi:10.1097/01.ju.0000150062.60633.b2. PMID 15643213.
- Rempe S, Hayden JM, Robbins RA, Hoyt JC; Hayden; Robbins; Hoyt (December 2007). "Tetracyclines and pulmonary inflammation". Endocr Metab Immune Disord Drug Targets. 7 (4): 232–6. doi:10.2174/187153007782794344. PMID 18220943.
- Urbano P, Urbano F; Urbano (2007). "Nanobacteria: facts or fancies?". PLOS Pathogens. 3 (5): e55. doi:10.1371/journal.ppat.0030055. PMC . PMID 17530922.
- Urbano P, Urbano F; Urbano (2007). "Nanobacteria: Facts or Fancies?". PLOS Pathogens. PLOS Pathogens. 3 (5): e55. doi:10.1371/journal.ppat.0030055. PMC . PMID 17530922.
- Michael Hopkin (2008). "Nanobacteria theory takes a hit". Nature. Retrieved 2008-04-29.
- Martel J, Young JD; Young (April 2008). "Purported nanobacteria in human blood as calcium carbonate nanoparticles". Proc. Natl. Acad. Sci. U.S.A. 105 (14): 5549–54. Bibcode:2008PNAS..105.5549M. doi:10.1073/pnas.0711744105. PMC . PMID 18385376.
- Dhar NB, Shoskes DA (2007). "New therapies in chronic prostatitis". Curr Urol Rep. 8 (4): 313–8. doi:10.1007/s11934-007-0078-5. PMID 18519016.
- Capodice JL, Bemis DL, Buttyan R, Kaplan SA, Katz AE (2005). "Complementary and alternative medicine for chronic prostatitis/chronic pelvic pain syndrome". Evid Based Complement Alternat Med. 2 (4): 495–501. doi:10.1093/ecam/neh128. PMC . PMID 16322807.
- Herati AS, Moldwin RM (2013). "Alternative therapies in the management of chronic prostatitis/chronic pelvic pain syndrome". World J Urol. 31 (4): 761–6. doi:10.1007/s00345-013-1097-0. PMID 23740129.
- Leskinen MJ; Vainionp R; Syrjnen S; et al. (2003). "Herpes simplex virus, cytomegalovirus, and papillomavirus DNA are not found in patients with chronic pelvic pain syndrome undergoing radical prostatectomy for localized prostate cancer". Urology. 61 (2): 397–401. doi:10.1016/S0090-4295(02)02166-0. PMID 12597955.
- Benson PJ, Smith CS; Smith (1992). "Cytomegalovirus prostatitis". Urology. 40 (2): 165–7. doi:10.1016/0090-4295(92)90520-7. PMID 1323895.
- Mastroianni A, Coronado O, Manfredi R, Chiodo F, Scarani P; Coronado; Manfredi; Chiodo; Scarani (1996). "Acute cytomegalovirus prostatitis in AIDS". Genitourinary medicine. 72 (6): 447–8. doi:10.1136/sti.72.6.447. PMC . PMID 9038649.
- McKay TC, Albala DM, Sendelbach K, Gattuso P; Albala; Sendelbach; Gattuso (1994). "Cytomegalovirus prostatitis. Case report and review of the literature". International urology and nephrology. 26 (5): 535–40. doi:10.1007/bf02767655. PMID 7860201.
- Doble A, Harris JR, Taylor-Robinson D; Harris; Taylor-Robinson (1991). "Prostatodynia and herpes simplex virus infection". Urology. 38 (3): 247–8. doi:10.1016/S0090-4295(91)80355-B. PMID 1653479.
- Leue, C; Kruimel, J; Vrijens, D; Masclee, A; van Os, J; van Koeveringe, G (March 2017). "Functional urological disorders: a sensitized defence response in the bladder-gut-brain axis". Nature Reviews. Urology. 14 (3): 153–163. doi:10.1038/nrurol.2016.227. PMID 27922040.
- "Anderson goes". Australian Broadcasting Corporation Transcript. Retrieved 2008-05-12.
- The Intimate Sex Lives of Famous People. Doubleday. 2008. ISBN 9781932595291. Retrieved 2010-12-21.
- Allison Reitz (July 2009). "John Cleese tour pays the 'Alimony' with West Coast comedy shows". tickenews.com. Archived from the original on 2009-07-28. Retrieved 2009-07-28.
The star of Monty Python and "A Fish Called Wanda" has been diagnosed with prostatitis, the inflammation of the prostate gland and is undergoing treatment.
- Roger Ebert. "The whole truth from Vincent Gallour Flies". Chicago Sun Times. Retrieved 2008-05-30.
- "Glenn Gould as Patient". Archived from the original on 2008-06-07. Retrieved 2008-05-12.
- Dallek, Robert (2003). An Unfinished Life: John F. Kennedy 1917-1963. Boston: Little, Brown. p. 123. ISBN 0-316-17238-3.
- "The Howard Stern Show for September 4, 2007". Howard Stern. Retrieved 2008-05-12.
- "The Howard Stern Show for September 5, 2007, PULLING OUT A PLUM". Howard Stern. Retrieved 2008-05-12.
- Leavitt, David (2008-05-11). "Styron's Choices". NY Times. Retrieved 2008-05-12.