Complications of Chronic Prostatitis Satya Srini Vasan Current Bladder Dysfunction Reports ISSN 1931-7212 Volume 7 Number 2 Curr Bladder Dysfunct Rep (2012) 7:141-149 DOI 10.1007/s11884-012-0132-0 1 23 Your article is protected by copyright and all rights are held exclusively by Springer Science+Business Media, LLC. This e-offprint is for personal use only and shall not be selfarchived in electronic repositories. If you wish to self-archive your work, please use the accepted author’s version for posting to your own website or your institution’s repository. You may further deposit the accepted author’s version on a funder’s repository at a funder’s request, provided it is not made publicly available until 12 months after publication. 1 23 Author's personal copy Curr Bladder Dysfunct Rep (2012) 7:141–149 DOI 10.1007/s11884-012-0132-0 INFECTIOUS BLADDER DYSFUNCTION (MS MOURAD, SECTION EDITOR) Complications of Chronic Prostatitis Satya Srini Vasan Published online: 5 April 2012 # Springer Science+Business Media, LLC 2012 Abstract Chronic prostatitis (CP) is a pelvic condition in men that needs to be distinguished from other forms of prostatitis, such as acute and chronic bacterial prostatitis. CP is characterized by pelvic or perineal pain lasting longer than 3 months without evidence of urinary tract infection. Symptoms may wax and wane and pain may radiate to the back and perineum, causing discomfort while sitting. Dysuria, frequency, urgency, arthralgia, myalgia, unexplained fatigue, abdominal pain, and burning sensation in the penis may be present. Post-ejaculatory pain, mediated by nerves and muscles, is a hallmark of the condition and serves to distinguish CP/chronic pelvic pain syndrome (CPPS) patients from men with benign prostatic hyperplasia and healthy men. Some patients report low libido, sexual dysfunction, and erectile difficulties. The symptoms of CP/ CPPS appear to result from interplay between psychological factors and dysfunction in the immune, neurological, and endocrine systems. Some researchers have suggested that CPPS is a form of painful bladder syndrome/interstitial cystitis (PBS/IC). Therapies shown to be effective in treating IC/PBS (eg, quercetin) have shown some efficacy in CP/ CPPS. Recent research has focused on genomic and proteomic aspects of the related conditions. There are no definitive diagnostic tests for CP/CPPS. This is a poorly understood disorder, even though it accounts for 90% to 95% of prostatitis diagnoses. Its peak incidence is in men 35 to 45 years old. In 2007, the National Institute of Diabetes and Digestive and Kidney Diseases began using the umbrella term urologic chronic pelvic pain syndromes to refer to pain S. S. Vasan (*) Ankur Health Care Private Limited; Manipal Andrology and Reproductive Services (MARS), Bangalore, India e-mail: [email protected] syndromes associated with the bladder (eg, IC/PBS) and prostate gland (eg, CP/CPPS). The prognosis for CP/CPPS has improved greatly with the advent of multimodal treatment, including phytotherapy, pelvic nerve myofascial trigger point release, anxiety control, and chronic pain therapy. Keywords Chronic prostatitis . Complications . Treatment . Bladder dysfunction . Chronic pelvic pain syndrome . Management . Diagnosis . PSA . Bacterial prostatitis . Interstitial cystitis . Chronic urethritis . Cancer . Painful bladder syndrome . CP/CPPS . Ejaculatory pain Introduction Prostatitis, an inflammatory condition of the prostate formerly known as prostatodynia, has been classified by the National Institutes of Health (NIH) into four categories [1]: & & & & Category 1: acute bacterial prostatitis Category 2: chronic bacterial prostatitis Category 3: chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS) Category 4: asymptomatic inflammatory prostatitis. Acute bacterial prostatitis is characterized by pain in the pelvic area and during ejaculation. Chronic bacterial prostatitis is due to chronicity of bacterial infection with mild, moderate, or severe symptoms, which is episodic. CP/CPPS is a term used to designate unexplained chronic pelvic pain in men. These men present with or without irritative voiding symptoms and pain located in the groin, genitalia, or perineum without bacteriuria or pyuria. Additionally, these men can present with recurrent urinary tract infection (UTI), ejaculatory pain, and erectile dysfunction. Asymptomatic inflammatory prostatitis is a condition in which there is Author's personal copy 142 Curr Bladder Dysfunct Rep (2012) 7:141–149 inflammation of the prostate with elevation of prostatespecific antigen (PSA) and an inflamed prostate, but no symptoms of prostatitis. CP/CPPS is a clinical syndrome defined primarily on the basis of urologic symptoms and/or pain or discomfort in the pelvic region. Despite the use of the term prostatitis, it is unclear to what degree the prostate is the source of symptoms [2]. & & & & & Trichomonas spp Candida spp Chlamydia trachomatis Ureaplasma urealyticum Mycoplasma hominis Fastidious Bacteria in Chronic Pelvic Pain Syndrome Epidemiology The annual prevalence in the general population of CPPS is 0.5% [3], though the overall prevalence of symptoms suggestive of CP/CPPS is 6.3% [4]. CP most commonly affects men older than 50 years of age [4]. Etiology The prostate anatomically has multiple ducts that exhibit nondependent drainage, which potentiates the chronicity of an infection. Prostate enlargement is natural with ageing, leading to bladder outlet obstruction with higher pressures during voiding, which leads to urinary reflux. Though refluxing urine is sterile, it can induce chemical irritation, which could initiate tubular fibrosis and prostatic stone formation, leading to blocking of secretions due to intraductal obstruction. Chronic nonbacterial prostatitis may in certain cases actually be due to an occult, chronic bacterial infection, and some men are at higher risk than others [5]. The common infections are due to uropathogenic Escherichia coli, as certain strains have specific capability of penetrating into prostate cells. Further strains such as Propionibacterium acnes can be detected only via sophisticated genesequencing and polymerase chain reaction assay technology, which makes the diagnosis difficult. In the prostate cells, they trigger a genetically linked reaction that sustains the pain by immunologic and/or neurological mechanisms, even after the bacteria have been eradicated, which might explain why antibiotics are generally not helpful in CP. Bacteria may also resist the body’s defenses, detection techniques, and antibiotic treatment by getting entrenched in a microscopic slime layer called an exopolysaccharide matrix biofilm. By forming these biofilms within the prostate, E. coli and related bacterial pathogens may cause chronic treatment-resistant prostatitis [6]. Other causative organisms include the following: & & & & & Klebsiella pneumoniae Pseudomonas aeruginosa Proteus spp Staphylococcus spp Enterococcus spp Among the fastidious bacteria (ie, bacteria that cannot be isolated on standard culture media) that have been implicated in CPPS are C. trachomatis, the genital mycoplasmas (ie, U. urealyticum, M. hominis, Mycoplasma genitalium), a protozoan (ie, Trichomonas vaginalis), Neisseria gonorrhoeae, genital tract viruses (eg, herpes simplex virus types 1 and 2, cytomegalovirus), fungi, anaerobic bacteria, and gram-positive bacteria [7]. Key Postulates & & & & & An imbalance between proinflammatory cytokines and endogenous cytokine inhibitors. Histologic signs of inflammation were found in one third of patients diagnosed with CPPS who underwent prostatic biopsy, according to Pontari and Ruggieri’s report, suggesting an extraprostatic etiology for CPPS. Genetic predisposition due to differences in DNA sequences at chromosomal sites that regulate the production and action of cytokines. In some men, it is postulated that a breakdown in the mechanism whereby testosterone inhibits prostatic inflammation may lead to CPPS. An increase in nerve growth factor (NGF), leading to an increase in the number and the sensitivity of the pelvic nerves that transmit pain. Several other causes have been hypothesized for CPPS, including: 1. Stress-driven hypothalamic-pituitary-adrenal axis dysfunction and adrenocortical hormone (endocrine) abnormalities [8, 9]. 2. Neurogenic inflammation leading to neuropathy and spastic hyperactivity due to an occult neural etiology or an acquired functional voiding disorder [10–12]. It is hypothesized that dysregulation of the local nervous system due to past trauma, infection, or an anxious disposition and chronic pelvic testing leads to inflammation that is mediated by substances released by nerve cells (eg, substance P). 3. Myofascial pain syndrome [13, 14]. Myofascial pain syndrome is an entity in which past inflammation leads to a secondary reflex triggering of spasm in the musculature of the pelvic floor, leading to varied symptomatology [15]. Author's personal copy Curr Bladder Dysfunct Rep (2012) 7:141–149 Immunology and Climate in Chronic Pelvic Pain Syndrome Several studies now demonstrate that men with CP/CPPS show evidence of having a “pan-pelvic hypersensitivity syndrome.” Using the fibromyalgia tender point scale, men with CP/CPPS tend to be more tender than normal, not only in the pelvic region, but also at every other point throughout their entire bodies. Stromal cells in benign prostatic hyperplasia (BPH) tissue have been shown to be capable of acting as antigen-presenting cells and activating CD4+ lymphocytes, as well as producing interleukins [16]. Whatever causes CP/ CPPS leads to a serious and hard-to-treat hypersensitivity of the entire central nervous system. This difference in lowered pain tolerance holds true whether or not the CP/CPPS patient was experiencing a flare-up of prostatitis [17]. The ambient temperature plays a role, as cold is frequently reported as causing symptom aggravation, and heat is often reported to be ameliorating [18]. It appears that cold is one of the factors that can trigger a process resulting in CP/CPPS [11]. Cold also causes aggravation of symptoms and can initiate a relapse [19, 20]. History and Physical Examination An NIH collaborative panel proposed the Chronic Prostatitis Symptom Index (NIH-CPSI), which is calculated using a series of 9 questions that contain 21 items and is used to assess patient history in a standardized and quantifiable format. These questions are provided below [21]. Physical examination in prostatitis shows: & & & & Mildly tender, nodular, or normal gland on digital rectal examination Suprapubic tenderness during acute episodes Tight anal sphincter on digital rectal examination Normal examination between acute episodes The value of this examination is to exclude other diagnoses, such as prostate cancer, chronic urethritis/meatitis, and granulomatous prostatitis. Chronic Pelvic Pain Syndrome Versus Interstitial Cystitis Unfortunately, there is no diagnostic test that can definitively establish or exclude the diagnosis of CPPS or interstitial cystitis. In 2004, Forrest and Schmidt reviewed a series of 92 men diagnosed with interstitial cystitis, most of whom had been referred for urologic evaluation with an initial diagnosis of CP (54%) or BPH (23%) [22]. Interstitial cystitis had been diagnosed in these patients according to 143 standard National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD) criteria and confirmed by the presence of severe glomerulations or Hunner ulcers on the bladder wall after hydrodistention. Forrest and Schmidt cautioned that the symptoms of interstitial cystitis closely parallel those of CP/CPPS. The patients’ presenting symptoms were often only mild discomfort in the suprapubic area. However, their symptoms rapidly worsened within less than 3 years, they had marked suprapubic pain, severe dysuria, and debilitating urinary frequency. Sexual dysfunction was an issue for 60% of these men, with painful ejaculation being the most frequently expressed symptom. Low back pain, perineal pain, and testicular pain were reported by 50% of these patients. Symptoms were so severe that total cystectomy was performed as a last resort in two of these patients. (As a side note, these researchers observed an unusually high prevalence of interstitial cystitis among Native American [Cherokee] men.) [22]. If cystoscopy is planned, it is done under anesthesia and includes taking a bladder biopsy and hydrodistention to search for indicative signs of interstitial cystitis [23]. Chronic Pelvic Pain Syndrome Versus Chronic Urethritis The distinction between chronic urethritis and CP/CPPS can prove problematic, an issue discussed by Krieger and Riley [24]. Of the seven symptoms evaluated in the NIH-CPSI, three are common to both populations: penile pain, urinary frequency, and dysuria. The remaining four symptoms are typical of CP/CPPS: perineal pain, pain in testicles, pain in suprapubic area, and pain upon ejaculation. Conversely, urethral discharge was characteristic of nongonococcal urethritis (NGU) but was not specifically reported in cases of CP/CPPS. Urethral white blood cells were identified in all patients with NGU and in 50% of those with CP/CPPS. Chronic Pelvic Pain Syndrome Versus Cancer Transitional cell cancer, carcinoma in situ of the bladder, prostate cancer, neoplasms of the rectum and gastrointestinal tract, and rare tumors of other pelvic organs have manifested as irritative prostatic symptoms and CPPS and must be considered during diagnosis. Standard teaching has been that men with CPPS have no increased risk of prostate cancer. However, a study from Case Western Reserve revealed that patients who underwent an initial prostate biopsy that was negative for cancer but positive for CP were at higher risk of subsequently developing cancer than men with prostatic inflammation [25]. Author's personal copy 144 However, the researchers did not recommend any change in current recommendations, pending confirmatory studies. Meanwhile, patients with CPPS should adhere strictly to standard recommendations for prostate cancer screening. Curr Bladder Dysfunct Rep (2012) 7:141–149 A 2010 study found that NGF could also be used as a biomarker of the condition [37•]. Men with CP/CPPS are more likely than the general population to suffer from chronic fatigue syndrome [38] and irritable bowel syndrome. Diagnosis Imaging Studies There are no definitive diagnostic tests for CP/CPPS. The presence of an inordinate number of white blood cells in the expressed prostatic secretions (EPS) and/or bacteria on gram stain, and/or a heavy, nearly pure growth of a known bacterial pathogen on culture indicates a diagnosis of bacterial prostatitis. However, contamination from the urethra, an external site, or a source of infection in the upper urinary tract can lead to a false-positive result, while errors in collection or processing can lead to a false-negative result. The NIH Chronic Prostatitis Cohort Study, in reviewing the screening results from 488 men with CP, CPPS, or both, found no reliable correlation between the leukocyte counts or the bacterial counts and the degree of symptomatology whether the analysis was performed on the EPS, the postmassage voided urine (ie, the third midstream bladder specimen [VB3]), or the ejaculate. The authors concluded that factors other than leukocytes and bacteria must contribute to symptom development in men with CPPS [26]. CP/CPPS may be inflammatory (category IIIa) or noninflammatory (category IIIb), based on levels of pus cells in EPS. In 2006, Chinese researchers found that men with categories IIIa and IIIb had significantly and similarly raised levels of the anti-inflammatory cytokine transforming growth factor-β1 and the proinflammatory cytokine interferon-γ in their EPS when compared with controls; therefore, measurement of these cytokines could be used to diagnose category III prostatitis [27]. 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, such as cytokines, are measured [28]. Analysis of urine and EPS for leukocytes is debatable, as the differentiation between inflammatory and noninflammatory subgroups of CP/CPPS is not useful [29]. The standard four-glass test may not be clinically accurate due to high prevalence of white blood cells and positive bacterial cultures in the asymptomatic control population [30]. The Meares-Stamey four-glass test is now rarely used [31]. Anothaisintawee et al. [32] suggested that a simplified premassage and postmassage test may prove more efficacious. Experimental tests that could be useful in the future include tests to measure semen and prostate fluid cytokine levels, with various studies having shown increases in markers for inflammation such as elevated levels of cytokines [33], myeloperoxidase [34], and chemokines [35, 36]. Because no diagnostic finding for CPPS has proven definitive, all imaging studies (eg, KUB radiography/ultrasound scan, intravenous pyelography, videocystourethrography, CT scanning, MRI, ultrasonography of the scrotum, transrectal ultrasonography of the prostate) are aimed at excluding the presence of other more definable and treatable causes of the patient’s symptoms and do not warrant universal application. Prostate-Specific Antigen Study PSA testing in men with CPPS symptoms may be helpful in distinguishing between chronic bacterial prostatitis (ie, an elevated PSA value) and prostatodynia (ie, a PSA value within the reference range), though this has not been established in a controlled study [39]. Uroflow and Urine Cytology Uroflow may show intermittency of flow and weakening of the urinary stream with a diminished peak urinary flow rate, and urethral pressure profile may show high maximum urethral closing pressure. Voided urine cytologies are indicated only in men with occupational exposure to known toxins or who exhibit persistent microhematuria. Prostate Biopsy Prostate biopsy is only useful in category IV sympatomatic inflammatory prostatitis with elevated PSA levels to exclude prostate cancer. Videourodynamics The main role of urodynamic studies is to rule out another underlying, unsuspected, but well-defined neuropathy amenable to treatment, which should justify the cost and discomfort associated with the procedure. Videourodynamic evaluation often reveals evidence of a spastic dysfunction of the bladder neck and prostatic urethra. Beyond helping to Author's personal copy Curr Bladder Dysfunct Rep (2012) 7:141–149 detect occult neuropathies, it may lead to a better understanding of the underlying voiding dysfunctions peculiar to select subsets of patients with this condition. Anal sphincter electromyography and/or sphincter function profiles, the reflex reactivity during cystometrography, and findings indicate the presence of hypertonicity and failure of the pelvic floor musculature to relax, which are signs of an underlying myofascial pain syndrome. Anothaisintawee et al. [40•] contend that dysfunctional voiding and intraprostatic reflux of urine may be initiating factors in the onset of CPPS type III. Additionally, by subcategorizing patients with CPPS type III based on the presence and the nature of abnormal urodynamic findings, an improved rationale for case-specific therapies may be forthcoming [41]. Cystoscopy Although the study results may be entirely normal, cystoscopy may reveal only nonspecific findings of minimal to mild inflammation and congestion in the area of the trigone and prostatic urethra. The main purpose of this intervention is to rule out the presence of other causes of the patient’s symptoms. The study is preferably done under general anesthesia, as it allows cold mucosal cup biopsies to rule out carcinoma in situ and for hydrodistention of the bladder to rule out interstitial cystitis. Management Counseling No known cure exists for CPPS, but treatments based on the cooperation of patient make this condition more bearable, and in some, it may improve or stabilize on its own. Reassure the patient that CPPS is a real physical condition, not an imagined one, is not cancer, is not life threatening, is not a venereal disease, and is not contagious. However, this devastating problem causes many psychological stresses for the patient; therefore, suggest medications to help calm the patient and offer consultation with a psychiatrist or psychologist [42•]. Treatments Traditionally, patients have been warned to avoid excessive intake of prostate irritants, such as tobacco, coffee, tea, soda, caffeine, spicy foods, and alcohol. Alkalinization of the urine seems to help some patients; however, highly alkaline urine can result in discomfort and dysuria. Sitz baths in a 145 deep tub rather than a shallow perineal dip may provide partial relief from acute exacerbations. Prostatic Massage In 1969, Winter recommended prostatic massage one to three times weekly for 3–4 weeks for chronic infection of the prostate. Although this maneuver has largely fallen out of favor due to little evidence, some still revert to it, albeit on a less frequent schedule, to provide supplementary symptomatic relief for select patients. Ejaculation Patients with enlarged, symptomatically congested glands are often advised that regular sexual intercourse may alleviate their symptoms, again with little objective evidence, and this is also objectionable to some patients on moral and religious grounds. Myofascial Release Therapy and Paradoxical Relaxation: Psychotherapeutic Treatment Technique Myofascial release therapy is a combination of internal and external trigger-point release that has proven more effective than standard external massage therapy alone. Paradoxical relaxation is a methodology used to train autonomic selfregulation and pelvic muscle tension release. Anderson et al. [43] have developed a protocol that employs a team composed of a urologist, psychologist, and physiotherapist to provide a multifaceted approach in treating patients with CPPS and educating them on how to effectively alleviate their symptoms. This “Stanford protocol” incorporates myofascial trigger point assessment and release therapy as well as paradoxical relaxation therapy [43]. Patients are taught the anatomy of the pelvic floor and lower abdomen and instructed on how to effectively manipulate their trigger points. Patients are also taught methods of relaxation in order to relieve autonomic dysfunction. A study showed an improvement in pain and urinary symptoms in 72% of patients with refractory CPPS, yet it is not widely accepted by urologists [43, 44]. Physical Medicine Therapist and Physiotherapist Pseudodyssynergia, documented on electromyographic and fluoroscopic findings, responded to treatment with biofeedback and behavior modification in 83% of cases [45]. Significant symptomatic relief has been achieved through modulation-based therapies such as biofeedback, αblockers, and sacral nerve stimulation [46]. A study by Anderson et al. [47] suggested that pain in at least a subset of patients with CP/CPPS may result from a Author's personal copy 146 variant of fibromyalgia. Spasm in these muscles causes referred pain to the penis, prostate, or neighboring pelvic structures. For example, pressing on a trigger point in the muscles of the pelvic floor (puborectalis/pubococcygeus muscles) was found to cause penile pain in the study [47]. Pharmacologic Management No analgesics are specifically appropriate in the treatment of prostatitis. Specialists at Stanford University found that 92% of men with refractory CPPS reported related erectile dysfunction, including problems with decreased libido (66%), pain upon ejaculation (56%), and ejaculatory dysfunction (31%) [48]. Medication Summary According to Meares [49–51], “Antibacterial agents are neither effective nor indicated in the treatment of nonbacterial prostatitis” [49–51]. If U. urealyticum or C. trachomatis infection is suggested, a trial treatment of antibiotics may be considered. Some patients with CPPS are maintained on long-term, low-dose regimens such as a single tablet of trimethoprimsulfamethoxazole daily. In some cases, patients experience symptomatic relief while on these regimens. Whether this is a reflection of the strong placebo effect associated with treatment of this condition or the result of suppression of an undetected pathogen is purely a matter of speculation. Studies suggest that beyond the placebo effect, certain antibiotics may actually be providing an objective anti-inflammatory and/or analgesic benefit to these patients. In screening for a bacterial etiology, the finding of grampositive organisms has often been dismissed as a contaminant. However, small studies have found evidence to suggest that anaerobes and gram-positive aerobes, even coagulasenegative staphylococci, may in fact be pathogens, and appropriate antibiotic therapy has proven effective in select cases [52]. In CPPS, the normal defense mechanisms that render bacteria harmless are defective, which may explain why prolonged courses of antibiotics sometimes provide symptomatic relief for men with CPPS despite the absence of bacteria that are traditionally considered pathogenic. Berger [53] observed, “Because of our inappropriate nomenclature of ‘prostatitis,’ (when it is neither an infection nor an inflammation) and the message given by our antibiotic treatment, many men end up thinking they have an incurable but unknown infection. Old habits are hard to change, but need to be replaced by patient education, and perhaps by physical education and pain-directed drug therapy.” In a controlled, randomized investigation by the Chronic Prostatitis Collaborative Research Network-2, pregabalin Curr Bladder Dysfunct Rep (2012) 7:141–149 failed to show an advantage in relieving discomfort, as measured by the NIH-CPSI. The problem was that while 47.2% of the men experienced significant (>6-point) relief when taking pregabalin, 35.8% of the men who were taking a placebo also experienced relief. Patients taking pregabalin fared better on the McGill Pain Questionnaire. Despite these findings, clinicians still hold that pregabalin may have a role in pain relief for select CP/CPPS patients. It is important to bear in mind that use of pregabalin is not US Food and Drug Administration approved for the treatment of CP/CPPS pain [54]. Alpha-Adrenergic Blockers These drugs by relieving the secondary smooth muscle spasm within the bladder neck and prostatic urethra, afford the patient greater comfort in voiding, and have become a mainstay in the symptomatic treatment of CPPS in men [49–51]. One study suggested an advantage to the use of α-blockers in combination with antibiotics over antibiotic therapy alone in the treatment of chronic bacterial prostatitis [54]. Randomized controlled trials in which benefit was found included the following drugs and doses: & & & & Alfuzosin (5 mg twice daily for 6 months) [55]. Alfuzosin, modified release 10 mg, may be used as an alternative but has not been evaluated. Tamsulosin (0.4 mg for 6 weeks) [56, 57]. Terazosin (1 mg for 4 days, 2 mg for 10 days, then 5 mg for 12 weeks [14 weeks total], or 5 mg for 8 weeks [58, 59], or 1–2 mg three times daily for 6 months [59]). Doxazosin (4 mg/d for 6 months) [60]. Other Treatments Limited evidence of effectiveness (from at least one randomized controlled trial) has been reported for the following investigational treatments (in alphabetical order): & & & & & & Finasteride (IbA) [61] Fluoxetine (IbA) [62] Mepartricin (IbA) [63] Pelvic electromagnetic therapy (IbA) [64] Prostat/poltit (pollen extract) (IbA) [65] Quercetin (IbA) [66]. The following investigational treatments are of unknown effectiveness and cannot be recommended because reported studies are case series, uncontrolled trials, or small randomized controlled trials showing no statistical benefit: & & & Aerobic exercise [67] Acupuncture [68] Allopurinol [69] Author's personal copy Curr Bladder Dysfunct Rep (2012) 7:141–149 & & & & & & & & & & & & & & Botulinum toxin A [70] Capsaicin [71] Cernilton (pollen extract) [72] Cooled transurethral microwave therapy [73] Corticosteroids [74] Ibuprofen [75] Pentosan polysulfate [76] Percutaneous tibial nerve stimulation [77] Sacral magnetic stimulation [78] Sertraline [79] Terpene mixture (Rowatinex) [80] Transurethral needle ablation (TUNA) [81] Urethro-anal stimulation [82] Zafirlukast [82]. Tricyclic antidepressants are sometimes tried in CP/ CPPS, but there are no published trials to support their use. They have been shown to be effective in some patients with other forms of chronic pain. Surgery: Transurethral Resection of the Prostate A widely held opinion among urologists is that transurethral resection of the prostate (TURP) should be reserved for patients who have experienced extreme, persistent symptoms over a protracted period, with no relief from nonoperative interventions. When TURP is undertaken, completing a thorough resection of all tissues down to the capsule is essential. The concern is that residual tissue causes obstruction of the ductal drainage from prostatic acini and might exacerbate the patient’s symptoms [83]. Conclusions CP/CPPS is a common condition affecting men of all ages. Because mortality and serious complications are extremely uncommon, CP/CPPS is primarily a quality-of-life disease; therefore, the patient’s perspective is of paramount importance. Interstitial cystitis and CP/CPPS are clinical syndromes characterized by pelvic pain with or without voiding symptoms such as urgency and frequency. There are many similarities in their epidemiology, adverse effects on quality of life, etiology/pathophysiology, natural history, and response to similar treatments. However, overlapping clinical definitions and similar entrance criteria for largescale cohort studies make comparisons problematic. Recent studies have shown that CP/CPPS takes a substantial toll on physical and mental health. As with other non–life-threatening diseases, the goal of treatment is to maximize quality and not quantity of life. Scientifically validated methods to measure patients’ health-related quality of life have been 147 applied in other urological diseases, such as BPH and interstitial cystitis; the same process is now under way in the study of CP/CPPS. Newer efforts to classify pelvic pain syndromes should help in our recognition that interstitial cystitis and CP/CPPS likely are not organ-specific syndromes, but rather urogenital manifestations of regional or systemic abnormalities. Disclosure No potential conflicts of interest relevant to this article were reported. References Papers of particular interest, published recently, have been highlighted as: • Of importance 1. http://www.chronicprostatitis.com/nihdef.html 2. Potts JM. Chronic pelvic pain syndrome: a non-prostatocentric perspective. World J Urol. 2003;21:54. 3. Taylor BC, Noorbaloochi S, McNaughton-Collins M, et al. Excessive antibiotic use in men with prostatitis. Am J Med. 2008;121 (5):444–9. 4. Daniels NA, Link CL, Barry MJ, McKinlay JB. Association between past urinary tract infections and current symptoms suggestive of chronic prostatitis/chronic pelvic pain syndrome. J Natl Med Assoc. 2007;99(5):509–16. 5. NIH Summary Statement. NIDDK Workshop on Chronic Prostatitis, Bethesda, Md. December 1995. 6. Wagenlehner FM, Naber KG. Fluoroquinolone antimicrobial agents in the treatment of prostatitis and recurrent urinary tract infections in men. Curr Urol Rep. 2004;5(4):309–16. 7. 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