Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral and anal sphincter function. Part 4: Effectiveness of the motor reinnervation.

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelve months postdecentralization, eight underwent transfer of obturator nerve branches to pelvic nerve vesical branches, and sciatic nerve branches to pudendal nerves, followed by 10 mo recovery (ObNT-ScNT Reinn). The remaining four were euthanized 18 mo postdecentralization (Decentralized). Results were compared with 18 Controls. Squat-and-void postures were tracked during awake cystometry. None showed squat-and-void postures during the decentralization phase. Seven of eight ObNT-ScNT Reinn began showing such postures by 6 mo postreinnervation; one showed a return of defecation postures. Retrograde dyes were injected into the bladder and urethra 3 wk before euthanasia, at which point, roots and transferred nerves were electrically stimulated to evaluate motor function. Upon L2-L6 root stimulation, five of eight ObNT-ScNT Reinn showed elevated detrusor pressure and four showed elevated urethral pressure, compared with L7-S3 root stimulation. After stimulation of sciatic-to-pudendal transferred nerves, three of eight ObNT-ScNT Reinn showed elevated urethral pressure; all showed elevated anal sphincter pressure. Retrogradely labeled neurons were observed in L2-L6 ventral horns (in laminae VI, VIII, and IX) of ObNT-ScNT Reinn versus Controls in which labeled neurons were observed in L7-S3 ventral horns (in lamina VII). This data supports the use of nerve transfer techniques for the restoration of bladder function.NEW & NOTEWORTHY This data supports the use of nerve transfer techniques for the restoration of bladder function.

Nerve transfer for restoration of lower motor neuron-lesioned bladder function. Part 1: attenuation of purinergic bladder smooth muscle contractions.

This study determined the effect of pelvic organ decentralization and reinnervation 1 yr later on the contribution of muscarinic and purinergic receptors to ex vivo, nerve-evoked, bladder smooth muscle contractions. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, 8 were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers then euthanized 8-12 mo later. Four served as long-term decentralized only animals. Controls included six sham-operated and three unoperated animals. Detrusor muscle was assessed for contractile responses to potassium chloride (KCl) and electric field stimulation (EFS) before and after purinergic receptor desensitization with α, ß-methylene adenosine triphosphate (α,ß-mATP), muscarinic receptor antagonism with atropine, or sodium channel blockade with tetrodotoxin. Atropine inhibition of EFS-induced contractions increased in decentralized and reinnervated animals compared with controls. Maximal contractile responses to α,ß-mATP did not differ between groups. In strips from decentralized and reinnervated animals, the contractile response to EFS was enhanced at lower frequencies compared with normal controls. The observation of increased blockade of nerve-evoked contractions by muscarinic antagonist with no change in responsiveness to purinergic agonist suggests either decreased ATP release or increased ecto-ATPase activity in detrusor muscle as a consequence of the long-term decentralization. The reduction in the frequency required to produce maximum contraction following decentralization may be due to enhanced nerve sensitivity to EFS or a change in the effectiveness of the neurotransmission.

The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS).

AIMS: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study-the Symptom Patterns Study (SPS)-to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments. METHODS: This multisite cohort study of males and females with UCPPS features a run-in period of four weekly web-based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol. RESULTS: Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re-enrolled from the first MAPP Network cohort study (2009-2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow-up of the cohort is ongoing. CONCLUSIONS: This comprehensive characterization of a large UCPPS cohort with extended follow-up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions.

Nerve transfer for restoration of lower motor neuron-lesioned bladder and urethra function: establishment of a canine model and interim pilot study results.

OBJECTIVE: Previous patient surveys have shown that patients with spinal cord or cauda equina injuries prioritize recovery of bladder function. The authors sought to determine if nerve transfer after long-term decentralization restores bladder and sphincter function in canines. METHODS: Twenty-four female canines were included in this study. Transection of sacral roots and hypogastric nerves (S Dec) was performed in 6 animals, and 7 animals underwent this procedure with additional transection of the L7 dorsal roots (L7d+S Dec). Twelve months later, 3 L7d+S Dec animals underwent obturator-to-pelvic nerve and sciatic-to-pudendal nerve transfers (L7d+S Dec+Reinn). Eleven animals served as controls. Squat-and-void behaviors were tracked before and after decentralization, after reinnervation, and following awake bladder-filling procedures. Bladders were cystoscopically injected with Fluoro-Gold 3 weeks before euthanasia. Immediately before euthanasia, transferred nerves were stimulated to evaluate motor function. Dorsal root ganglia were assessed for retrogradely labeled neurons. RESULTS: Transection of only sacral roots failed to reduce squat-and-void postures; L7 dorsal root transection was necessary for significant reduction. Three L7d+S Dec animals showing loss of squat-and-void postures post-decentralization were chosen for reinnervation and recovered these postures 4-6 months after reinnervation. Each showed obturator nerve stimulation-induced bladder contractions and sciatic nerve stimulation-induced anal sphincter contractions immediately prior to euthanasia. One showed sciatic nerve stimulation-induced external urethral sphincter contractions and voluntarily voided twice following nonanesthetized bladder filling. Reinnervation was confirmed by increased labeled cells in L2 and the L4-6 dorsal root ganglia (source of obturator nerve in canines) of L7d+S Dec+Reinn animals, compared with controls. CONCLUSIONS: New neuronal pathways created by nerve transfer can restore bladder sensation and motor function in lower motor neuron-lesioned canines even 12 months after decentralization.

Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network.

Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, is characterized by chronic pain in the pelvic region or genitalia that is often accompanied by urinary frequency and urgency. Despite considerable research, no definite aetiological risk factors or effective treatments have been identified. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network uses a novel integrated strategy to characterize UCPPS as a systemic disorder that potentially involves multiple aetiologies. The first phase, MAPP I, included >1,000 participants who completed an intensive baseline assessment followed by a 12-month observational follow-up period. MAPP I studies showed that UCPPS pain and urinary symptoms co-vary, with only moderate correlation, and should be evaluated separately and that symptom flares are common and can differ considerably in intensity, duration and influence on quality of life. Longitudinal clinical changes in UCPPS correlated with structural and functional brain changes, and many patients experienced global multisensory hypersensitivity. Additionally, UCPPS symptom profiles were distinguishable by biological correlates, such as immune factors. These findings indicate that patients with UCPPS have objective phenotypic abnormalities and distinct biological characteristics, providing a new foundation for the study and clinical management of UCPPS.

Identification of novel non-invasive biomarkers of urinary chronic pelvic pain syndrome: findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

OBJECTIVE: To examine a series of candidate markers for urological chronic pelvic pain syndrome (UCPPS), selected based on their proposed involvement in underlying biological processes so as to provide new insights into pathophysiology and suggest targets for expanded clinical and mechanistic studies. METHODS: Baseline urine samples from Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study participants with UCPPS (n = 259), positive controls (PCs; chronic pain without pelvic pain, n = 107) and healthy controls (HCs, n = 125) were analysed for the presence of proteins that are suggested in the literature to be associated with UCPPS. Matrix metalloproteinase (MMP)-2, MMP-9, MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex (also known as Lipocalin 2), vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGF-R1) and NGAL were assayed and quantitated using mono-specific enzyme-linked immunosorbent assays for each protein. Log-transformed concentration (pg/mL or ng/mL) and concentration normalized to total protein (pg/µg) values were compared among the UCPPS, PC and HC groups within sex using the Student's t-test, with P values adjusted for multiple comparisons. Multivariable logistic regression and receiver-operating characteristic curves assessed the utility of the biomarkers in distinguishing participants with UCPPS and control participants. Associations of protein with symptom severity were assessed by linear regression. RESULTS: Significantly higher normalized concentrations (pg/µg) of VEGF, VEGF-R1 and MMP-9 in men and VEGF concentration (pg/mL) in women were associated with UCPPS vs HC. These proteins provided only marginal discrimination between UCPPS participants and HCs. In men with UCCPS, pain severity was significantly positively associated with concentrations of MMP-9 and MMP-9/NGAL complex, and urinary severity was significantly positively associated with MMP-9, MMP-9/NGAL complex and VEGF-R1. In women with UCPPS, pain and urinary symptom severity were associated with increased normalized concentrations of MMP-9/NGAL complex, while pain severity alone was associated with increased normalized concentrations of VEGF, and urinary severity alone was associated with increased normalized concentrations of MMP-2. Pain severity in women with UCPPS was significantly positively associated with concentrations of all biomarkers except NGAL, and urinary severity with all concentrations except VEGF-R1. CONCLUSION: Altered levels of MMP-9, MMP-9/NGAL complex and VEGF-R1 in men, and all biomarkers in women, were associated with clinical symptoms of UCPPS. None of the evaluated candidate markers usefully discriminated UCPPS patients from controls. Elevated VEGF, MMP-9 and VEGF-R1 levels in men and VEGF levels in women may provide potential new insights into the pathophysiology of UCPPS.

Use of Age and Medical Comorbidity to Assess Long-term Other-cause Mortality Risk in a Cohort of Men Undergoing Prostate Biopsy at an Academic Medical Center.

OBJECTIVE: To assess life expectancy and biopsy outcomes in men undergoing prostate biopsy at an academic medical center. METHODS: We analyzed men who underwent prostate biopsy at our medical center between July 2012 and June 2014. Long-term other-cause mortality risk was determined using survival tables. Indications for biopsy and biopsy outcomes were assessed, and compared among men with varying mortality risks. RESULTS: A total of 417 men underwent prostate biopsy, in whom 14-year other-cause mortality risk ranged from 9% to 74%. One hundred ninety-three men (46.3%) were considered low-mortality risk (<40% risk of 14-year mortality), 131 (31.4%) intermediate risk (41%-55% 14-year mortality), and 93 (22.3%) high risk (>55% 14-year mortality). Of the 417 patients who underwent biopsy, 149 (35.7%) were found to have prostate cancer. There was no significant difference in the rate of positive biopsies (P = .72), distribution of Gleason scores (P = .60), or percentage of positive biopsy cores (P = .74) between mortality risk groups. However, by UCSF Cancer of the Prostate Risk Assessment score, there was significant trend toward higher-risk prostate cancer in men with intermediate and high-mortality risk (P = .04). CONCLUSION: In this analysis, a large number of men with limited life expectancies underwent prostate biopsy. The majority of these men had negative biopsies or low-risk cancers, suggesting that they were unlikely to benefit from biopsy. To avoid potentially unnecessary prostate biopsies, the practitioner must give serious consideration to a patient's age and medical comorbidities before making a recommendation as to whether biopsy should be performed.

Painful Bladder Filling and Painful Urgency are Distinct Characteristics in Men and Women with Urological Chronic Pelvic Pain Syndromes: A MAPP Research Network Study.

PURPOSE: We describe bladder associated symptoms in patients with urological chronic pelvic pain syndromes. We correlated these symptoms with urological, nonurological, psychosocial and quality of life measures. MATERIALS AND METHODS: Study participants included 233 women and 191 men with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome in a multicenter study. They completed a battery of measures, including items asking whether pain worsened with bladder filling (painful filling) or whether the urge to urinate was due to pain, pressure or discomfort (painful urgency). Participants were categorized into 3 groups, including group 1-painful filling and painful urgency (both), 2-painful filling or painful urgency (either) and 3-no painful filling or painful urgency (neither). RESULTS: Of the men 75% and of the women 88% were categorized as both or either. These bladder characteristics were associated with more severe urological symptoms (increased pain, frequency and urgency), a higher somatic symptom burden, depression and worse quality of life (3-group trend test each p<0.01). A gradient effect was observed across the groups (both>either>neither). Compared to those in the neither group men categorized as both or either reported more frequent urological chronic pelvic pain syndrome symptom flares, catastrophizing and irritable bowel syndrome, and women categorized as both or either were more likely to have a negative affect and chronic fatigue syndrome. CONCLUSIONS: Men and women with bladder symptoms characterized as painful filling or painful urgency had more severe urological symptoms, more generalized symptoms and worse quality of life than participants who reported neither characteristic, suggesting that these symptom characteristics might represent important subsets of patients with urological chronic pelvic pain syndromes.

The MAPP research network: design, patient characterization and operations.

BACKGROUND: The "Multidisciplinary Approach to the Study of Chronic Pelvic Pain" (MAPP) Research Network was established by the NIDDK to better understand the pathophysiology of urologic chronic pelvic pain syndromes (UCPPS), to inform future clinical trials and improve clinical care. The evolution, organization, and scientific scope of the MAPP Research Network, and the unique approach of the network's central study and common data elements are described. METHODS: The primary scientific protocol for the Trans-MAPP Epidemiology/Phenotyping (EP) Study comprises a multi-site, longitudinal observational study, including bi-weekly internet-based symptom assessments, following a comprehensive in-clinic deep-phenotyping array of urological symptoms, non-urological symptoms and psychosocial factors to evaluate men and women with UCPPS. Healthy controls, matched on sex and age, as well as "positive" controls meeting the non-urologic associated syndromes (NUAS) criteria for one or more of the target conditions of Fibromyalgia (FM), Chronic Fatigue Syndrome (CFS) or Irritable Bowel Syndrome (IBS), were also evaluated. Additional, complementary studies addressing diverse hypotheses are integrated into the Trans-MAPP EP Study to provide a systemic characterization of study participants, including biomarker discovery studies of infectious agents, quantitative sensory testing, and structural and resting state neuroimaging and functional neurobiology studies. A highly novel effort to develop and assess clinically relevant animal models of UCPPS was also undertaken to allow improved translation between clinical and mechanistic studies. Recruitment into the central study occurred at six Discovery Sites in the United States, resulting in a total of 1,039 enrolled participants, exceeding the original targets. The biospecimen collection rate at baseline visits reached nearly 100%, and 279 participants underwent common neuroimaging through a standardized protocol. An extended follow-up study for 161 of the UCPPS participants is ongoing. DISCUSSION: The MAPP Research Network represents a novel, comprehensive approach to the study of UCPPS, as well as other concomitant NUAS. Findings are expected to provide significant advances in understanding UCPPS pathophysiology that will ultimately inform future clinical trials and lead to improvements in patient care. Furthermore, the structure and methodologies developed by the MAPP Network provide the foundation upon which future studies of other urologic or non-urologic disorders can be based. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01098279 "Chronic Pelvic Pain Study of Individuals with Diagnoses or Symptoms of Interstitial Cystitis and/or Chronic Prostatitis (MAPP-EP)". http://clinicaltrials.gov/show/NCT01098279.

Etiology of chronic prostatitis/chronic pelvic pain syndrome: psychoimmunoneurendocrine dysfunction (PINE syndrome) or just a really bad infection?

PURPOSE: To review the etiology and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: A literature review for the years 1985-2012 was performed using the MEDLINE database of the United States National Library of Medicine. RESULTS: The evidence for ongoing infection in men with CP/CPPS is lacking. However, men with CP/CPPS are twice as likely to have had a sexually transmitted disease (STD), and bacteria from men with CP/CPPS may be phenotypically different from those that cause cystitis or acute prostatitis. Evidence continues to support an alteration in both the afferent and efferent autonomic nervous systems. Functional brain imaging suggests changes in the gray matter as well as the importance of the anterior insula and anterior cingulated gyrus in pain processing. Neural function can be modulated by immune and endocrine factors. Alterations in cytokine function and autoimmunity appear to play a role in the immune dysfunction. Alterations in the hypothalamic-pituitary-adrenal axis can mediate the endocrine effects, similar to many other chronic pain conditions. Genetics may play a role in who may develop chronic pain after an initial insult. Finally, any biological changes must then be processed through the psychosocial environment, including the tendency to catastrophize, and degree of spousal support, to produce a given individual patient's pain experience. CONCLUSIONS: Infection with atypical bacteria or sequelae of an STD may lead to CP/CPPS in some men. Such a biological insult in the context of alterations in psychoimmunoneurendocrine factors produces the chronic pain experience.

Evaluation and management of gunshot wounds of the penis: 20-year experience at an urban trauma center.

BACKGROUND: Although gunshot injuries to the penis occur relatively infrequently in patients with penetrating trauma, they often present dilemmas of subsequent evaluation and management. We review our extensive experience with gunshot wounds to the penis at a high volume urban trauma center. METHODS: The urologic trauma database was retrospectively reviewed to extract and compile information from the records of 63 patients treated for gunshot wounds to the penis. Data were accumulated for a 20-year period from 1985 to 2004 with regard to findings on physical examination, diagnostic evaluation, associated injuries, management, and outcome. We detail our technique of penile exploration and artificial erection in the management of these injuries. RESULTS: Penile gunshot wounds were associated with additional injuries in 53 of 63 (84%) patients. A total of 48 (76%) patients were taken to the operating room and 44 (70%) penile explorations were performed. Evaluation included retrograde urethrogram in 50 of 63 (79%) patients and was diagnostic for urethral injury in 11 of 12 (92%) cases. Primary urethral repair was performed in 8 of 12 (67%) patients with urethral injury versus 4 of 12 (33%) who underwent urinary diversion by means of suprapubic cystotomy. CONCLUSIONS: Evaluation and management of gunshot wounds to the penis may potentially be complex. Retrograde urethrogram should be performed in all cases except the most insignificant and superficial wounds. We describe our technique of penile exploration and artificial erection, noting excellent results in patients for whom follow-up is available. Additional studies are needed to prospectively evaluate techniques for management of gunshot urethral injuries.

Chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis: are they related?

Interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome 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 effect on quality of life, etiology/pathophysiology, natural history, and response to similar treatments. However, overlapping clinical definitions and similar entrance criteria for large-scale cohort studies make comparisons problematic. Newer efforts to classify pelvic pain syndromes should help in our recognition that interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome likely are not organ-specific syndromes but urogenital manifestations of regional or systemic abnormalities.

Functional reinnervation of the canine bladder after spinal root transection and immediate end-on-end repair.

The goal of this study was to transect and immediately repair ventral roots, selected by their ability to stimulate bladder contraction, to assess the feasibility of bladder reinnervation in a canine model. Brain-derived neurotrophic factor (BDNF) was delivered via an osmotic pump (0.5 or 5 mg/mL) to a cuff surrounding the reanastomosis site to the two root bundles on one side. Electrodes were implanted bilaterally immediately proximal to the site of surgical reanastomosis. Results were compared to four root-intact, control animals that also received bilateral electrode implantation. At 6-12 months post-surgery, five of eight nerve transected and repaired animals showed increased pressure and bladder emptying during electrical stimulation of the repaired ventral roots contralateral to the BDNF delivery side. Nerve tracing studies one year postoperatively determined the repaired roots to be S1 and S2 and showed regrowth of axons from the spinal cord to nerve sites proximal to the repair site and to the bladder, and the presence of neurofilament-labeled axons growing across the ventral root repair site. In conclusion, transected ventral and dorsal roots in the sacral spine can be repaired and are capable of functionally reinnervating the urinary bladder. This feasibility study paves the way for future studies utilizing other more proximal motor nerves to bypass the transection site for bladder reinnervation.

Combined use of alpha-adrenergic and muscarinic antagonists for the treatment of voiding dysfunction.

PURPOSE: We provide an overview of the medical literature supporting the combined use of muscarinic and alpha-adrenergic antagonist therapy for the treatment of voiding dysfunction. MATERIALS AND METHODS: The MEDLINE database (1966 to 2004) of the United States National Library of Medicine was searched for pertinent studies. RESULTS: Although the mechanism of action of alpha-adrenergic antagonist therapy for voiding dysfunction has traditionally been assumed to be relaxation of the periurethral, prostatic and bladder neck smooth muscle, substantial evidence supports action at extraprostatic sites involved in micturition, including the bladder dome smooth muscle, peripheral ganglia, spinal cord and brain. Likewise the mechanism of action of anticholinergic therapy has been traditionally assumed to be inhibition of the M3 muscarinic receptor subtypes that mediate normal bladder contractions. However, M2 receptor mediates hypertrophied bladder contractions and there is evidence for an M2 component to the suprasacral control of voiding. CONCLUSIONS: Based on the physiology of alpha-adrenergic and muscarinic receptors the inhibition of each one would be expected to be more beneficial than that of either alone because they would work on 2 components of detrusor function. Patients who would likely benefit from this combination therapy are men with lower urinary tract symptoms, women with urgency/frequency syndrome (overactive bladder), patients with uninhibited bladder contractions due to neurogenic bladder, and patients with pelvic pain and voiding symptoms, ie interstitial cystitis and chronic prostatitis/chronic pelvic pain syndrome.

A case-control study of risk factors in men with chronic pelvic pain syndrome.

OBJECTIVE: To compare the demographic, behavioural, clinical and medical history characteristics of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and asymptomatic controls, to identify characteristics that might be associated with this syndrome. PATIENTS AND METHODS: Self-administered epidemiological questionnaires were completed by 463 men with CP/CPPS and 121 asymptomatic age-matched controls. We compared the prevalence of possible risk factors between men with CP/CPPS and controls, using generalized Mantel-Haenszel tests, and developed multivariate predictive models using logistic regression methods, adjusting for clustering by clinical centre within both methods. RESULTS: Compared to controls, men with CP/CPPS reported a significantly greater lifetime prevalence of nonspecific urethritis (12% vs 4%, P = 0.008), cardiovascular disease (11% vs 2%, P = 0.004), neurological disease (41% vs 14%, P < 0.001), psychiatric conditions (29% vs 11%, P < 0.001), and haematopoietic, lymphatic or infectious disease (41% vs 20%, P < 0.001). CONCLUSION: A wide range of self-reported medical conditions was associated with CP/CPPS. Further studies are necessary to determine whether they play a role in the pathogenesis of CP/CPPS.

Demographic and clinical characteristics of men with chronic prostatitis: the national institutes of health chronic prostatitis cohort study.

PURPOSE: We describe the study design of the National Institutes of Health Chronic Prostatitis Cohort (CPC) study characterizing men with chronic prostatitis/the chronic pelvic pain syndrome. MATERIALS AND METHODS: All 488 men screened into the CPC study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, was used to measure symptoms. A comprehensive history, physical examination and demographic profile were obtained from each participant. Generalized Mantel-Haenszel procedures were used to investigate baseline associations between selected factors and symptoms. RESULTS: Chronic prostatitis/chronic pelvic pain syndrome is a chronic syndrome affecting men over a wide age range. The majority of CPC study participants are white, well educated and affluent. However, lower education, lower income and unemployment were associated with more severe symptoms. Patients most frequently reported pain in the perineum and tenderness in the prostate. The highest self-reported diseases were genitourinary (55%), allergies (53%), neurological (40%) and hematopoietic, lymphatic or infectious (40%). This disease has a significant negative impact on mental and physical domains of quality of life. Almost all patients (95%) reported antimicrobial drug use. Of these 488 participants 280 (57%) reported the previous or current use of 5 or more categories of prostatitis related treatments. CONCLUSIONS: Chronic prostatitis/chronic pelvic pain syndrome is a multifactorial problem affecting men of all ages and demographics. Patients with the chronic pelvic pain syndrome have dismal quality of life and many have benefited only minimally from empirical, goal directed therapy. Long-term followup of this cohort may answer important questions on the natural treated history of this syndrome.