Mechanisms in prostatitis/chronic pelvic pain syndrome

PURPOSE: We reviewed the current literature on mechanisms involved in the pathogenesis of prostatitis/chronic pelvic pain syndrome (CPPS). MATERIALS AND METHODS: A literature review for the years 1966 to 2003 was performed using the MEDLINE database of the United States National Library of Medicine. RESULTS: National Institutes of Health categories I and II prostatitis result from identifiable prostatic infections, whereas patients with category IV are asymptomatic. The majority of symptomatic cases are category III or chronic prostatitis (CP)/CPPS. The etiology of CP/CPPS is unknown. The traditional marker of inflammation, namely white blood cells in prostatic fluids, does not correlate with the predominant symptom of pelvic pain. An imbalance toward increased proinflammatory and decreased anti-inflammatory cytokines has been implicated and a few studies have shown some correlation of this with pelvic pain. The imbalance in some men may result from polymorphisms at the cytokine loci. An autoimmune process may be involved and experimental evidence indicates that this can be under hormonal influence. Recent findings include possible defects in the androgen receptor. The prostate may not even be the source of the symptoms. Pelvic pain also correlates with the neurotrophin nerve growth factor implicated in neurogenic inflammation and central sensitization. Finally, psychological stress may produce measurable biochemical changes and influence the other processes. The role of normal prostatic bacterial flora in inciting the inflammatory response has also been reconsidered. CONCLUSIONS: The symptoms of CP/CPPS appear to result from an interplay between psychological factors and dysfunction in the immune, neurological and endocrine systems.     

Impact of post-ejaculatory pain in men with category III chronic prostatitis/chronic pelvic pain syndrome

PURPOSE: Chronic Pelvic Pain Syndrome (CPPS) is a common debilitating condition in which ejaculation relieves symptoms for some but exacerbates them in others. We studied ejaculatory pain in a cohort with CPPS to investigate associations with symptoms, quality of life and risk factors. MATERIALS AND METHODS: The 486 men in the National Institutes of Health Chronic Prostatitis Cohort study were stratified into 4 subgroups according to the presence of ejaculatory pain at baseline visit and at each of 3 monthly followup contacts. Subgroups were based on answers and labeled NO (always "no"), Nvar ("no" at baseline but "yes" or missing at least once), Yvar ("yes" at baseline but "no" or missing at least once) and YES (always "yes"). Demographic and quality of life data were obtained at baseline, together with medical and sexual history, symptoms, and cultures and microscopy of urine and seminal fluids. Associations among selected baseline risk factors, symptoms and post-ejaculatory pain were analyzed. RESULTS: Overall 128 men were classified as NO, 106 as Nvar, 137 as Yvar and 115 as YES. There was a progressive increase in baseline National Institutes of Health-Chronic Prostatitis Symptom Index total score (modified to exclude post-ejaculatory pain) from 18.5 for the NO subgroup to 25.5 for the YES subgroup (p <0.0001). Mental and physical quality of life were also progressively lower from the NO to the YES subgroup (p <0.001). There were no significant differences in white blood cell count or bacterial growth in urine, prostate fluid or semen among subgroups. Men in the YES subgroup were younger, more likely to live alone, had lower income and a greater variety of sexual practices than those without ejaculatory pain (NO subgroup). CONCLUSIONS: Patients with CPPS and persistent ejaculatory pain have more severe symptoms, are less likely to improve with time, and have differences in demographic and sexual history compared to other patients with CPPS.     

Acute bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: andrological implications

There is a consensus on the diagnostic management of bacterial prostatitis (acute and chronic). In chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) the diagnostic approach remains unclear, because inflammatory and noninflammatory CP/CPPS might be one entity with varying findings over time. The WHO definition of male accessory gland infection does not differentiate between prostatitis, epididymitis, and other inflammatory alterations of the urethral compartment. The definition therefore cannot be further accepted as a rational tool for the diagnosis of prostatitis and related diseases in urological andrology. Therapy in infectious prostatitis is standardised and antibiotics are the primary agents. Andrological implications are well defined, side-effects are minimal. CP/CPPS therapy has the goal to reduce pelvic pain. However, treatment regimens are not as standardised. Andrological side-effects are well defined and mainly due to the functional background of these agents.     

Seminal fluid analysis in chronic prostatitis/chronic pelvic pain syndrome

Prostatitis is a common cause of morbidity among adult men. There are more than 2,000,000 doctor visits per year in the United States, approximately half to urologists (Collins et al., 1998, J Urol 159:1224; Roberts et al., 1998, Urology 51:578; Krieger et al., 2003, Urology). The problem is that very few patients have obvious infections, or functional or structural abnormalities. The aim of this study is to examine our experience with seminal fluid analysis in this patient population, and to outline the potential utility of this examination in patient evaluation.     

Long-term results of multimodal therapy for chronic prostatitis/chronic pelvic pain syndrome

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome is a prevalent and multifactorial condition. Many patients have the condition for years despite conventional therapies. We assess the outcomes of multimodal therapy in patients with long-standing chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: A total of 53 patients with chronic prostatitis treated at our clinic with a minimum followup of 6 months were assessed by the National Institutes of Health-Chronic Prostatitis Symptom Index and by a global assessment score. Treatments included antibiotics, prostatic massage, anti-inflammatory phytotherapy, alpha-blockers and neuromuscular agents. RESULTS: Mean age patient was 45 years and median symptom history was 3.5 years. Based on localizing cultures, and microscopy of urine and prostatic fluid 13% of the cases were category II, 41% were category IIIa and 46% were category IIIb. Mean followup from the last visit was 417 days (range 185 to 1,247). Mean changes +/- SE from the initial to the final score on the National Institutes of Health-Chronic Prostatitis Symptom Index were 10.4 +/- 3.3 to 5.9 +/- 4.4 for pain, 4.2 +/- 2.9 to 2.0 +/- 2.7 for urinary, 8.2 +/- 2.9 to 4.7 +/- 3.4 for quality of life and 22.7 +/- 6.6 to 13.2 +/- 9.5 for total score (p <0.0001). Based on a global subjective assessment 43 of the patients (80%) were better, 8 were the same and 3 were worse. At final assessment 39% of the patients were on no therapy, 22% were on an alpha-blocker, 37% were on quercetin, 13% were on neuromuscular agents and 9% were on antibiotics. CONCLUSIONS: An approach using stepwise therapy with antibiotics, anti-inflammatories and neuromuscular agents can be successful in the majority of patients with long-standing chronic prostatitis.     

The trues behind TRUS in the setting of chronic prostatitis/chronic pelvic pain syndrome

ObjectiveWe sought to explore the yield of transrectal ultrasound (TRUS) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).Materials and methodsThe records of all patients, who were referred for TRUS caused by CP/CPPS, were retrospectively reviewed. Digital rectal examination (DRE) was performed before TRUS. The following parameters were recorded: prostatic length; width; height; volume; external border; peripheral zone (PZ); transitional zone (TZ); TZ/PZ border; seminal vesicles appearance (SV); presence of median lobe; dilation of vas deferens (VD) or ejaculatory duct (ED); and presence of significant postvoid residual (PVR). Unique sonographic findings, if present, were recorded as well. Data were compared to those of an age-matched control group that had undergone the same imaging for other reasons.ResultsTwo hundred and sixteen patients with suspected CP/CPPS underwent DRE and TRUS. Per DRE, their prostates appeared smaller and homogeneous compared with the control group. Differences seen in TRUS between the study and the control groups, respectively, were as follows: fewer irregularities, fewer hypoechoic areas in PZ; fewer cystic spaces, fewer enlarged median lobes in TZ; less ED dilation; more calcifications; more VD dilation; and more periurethral vascularity. No differences were seen in SV parameters and in PVR. None of the patients has been given different diagnosis or treatment following TRUS.ConclusionThe findings of TRUS studies in patients with suspected CP/CPPS are not pathognomonic for this entity, and TRUS is therefore considered as having very little yield in this setting.     

Development of an evidence-based cognitive behavioral treatment program for men with chronic prostatitis/chronic pelvic pain syndrome

Objectives Psychosocial factors reported by patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) promote greater pain, disability, and ultimately poorer quality of life (QOL). We targeted those parameters in the development of a cognitive-behavioral (CB) program designed specifically for CP/CPPS. Methods and materials Five NIH sponsored biopsychosocial studies examined predictors of pain, disability, and QOL in CP/CPPS men. Pain, urinary symptoms, QOL, depressive symptoms, catastrophic thinking about pain, perceived control over pain, pain-contingent resting as a pain coping measure, social support and interaction, sexual functioning, and relationship issues were assessed. These data showed that CB intervention for pain catastrophizing, pain contingent rest, social support and depressive symptoms is warranted for men with CP/CPPS Results An evidence based 8-week CB program was developed. The content of the CB sessions are defined in an instructional patient workbook for each of the weekly 1-h sessions. The CB program guides patients in examining the relationship between their symptom-based distress, their thinking at such times and the emotions linked with those thoughts, and their behavioral responses to their particular thinking style (e.g., illness vs. wellness focused). Patients complete such analyses by using a Reaction Record format, which also delineates new thinking/behavioral responses. Conclusions The CB program developed for CP/CPPS is the first comprehensive attempt to target specific evidence supported biopsychosocial variables for both symptom and QOL improvement in CP/CPPS and is expected to provide a useful tool for the clinical management of this chronic condition.     

A case-control study of chronic prostatitis/chronic pelvic pain syndrome and colorectal cancer

Study Type – Symptom prevalence (case control) Level of Evidence 2b What's known on the subject? and What does the study add? Associations are well established between intestinal infection/inflammation or inflammatory bowel diseases and colorectal cancer (CRC). Our study found an association between CRC and previously diagnosed chronic prostatitis/chronic pelvic pain syndrome. Patients with CRC had a 1.45‐fold higher risk of having a previous diagnosis of chronic prostatitis/chronic pelvic pain syndrome than controls. This phenomenon was found to be more prominent in subjects younger than 60 years.

OBJECTIVE

• ? To estimate the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and colorectal cancer (CRC) using a nationwide population‐based data set.

PATIENTS AND METHODS

• ? This case–control study used data sourced from the Taiwan Longitudinal Health Insurance Database.
• ? The cases comprised 2899 patients with CRC and 14 995 randomly selected subjects as controls.
• ? We used conditional logistic regression to examine the association between CRC and previous diagnosis of CP/CPPS.

RESULTS

• ? Of the sampled patients, 531(3.05%) had been diagnosed with CP/CPPS before the index date, with 123 (4.24% of the patients with CRC) coming from the cases and 408 individuals (2.81% of patients without CRC) coming from the controls.
• ? Conditional logistic regression analysis revealed that cases were more likely to have CP/CPPS than controls (odds ratio 1.45, 95% CI 1.17–1.79, P < 0.001) after adjusting for the monthly income, geographic location, urbanization level, hypertension, diabetes, renal disease, obesity and cystic kidney disease.
• ? In subgroup analysis, we found the magnitude of the association to be higher in subjects younger than 60 years (age 40–49, odds ratio 2.01; 95% CI 2.04–3.58 and aged 50–59, 2.40, 95% CI 1.48–3.87, both P < 0.001) than among other age groups.

CONCLUSION

• ? We conclude that CP/CPPS patients are at higher risk for CRC, especially in males under 60 years of age.

     

Prognosis of patients with new prostatitis/pelvic pain syndrome episodes

PURPOSE: Little is known about the natural history of nonbacterial prostatitis/male pelvic pain syndrome, the transition from acute to chronic pelvic pain and risk factors for chronicity. In this study we determined the course of symptoms after physician visits for new nonbacterial prostatitis/pelvic pain syndrome episodes, and determined predictors of symptom persistence 1 year later. MATERIALS AND METHODS: A total of 286 male health maintenance organization enrollees (87% white, mean age 46.7 years, 83% completed the 12-month followup) with recent physician visits for new prostatitis/pelvic pain episodes completed baseline, and 3, 6 and 12-month followup telephone interviews, including the National Institutes of Health Chronic Prostatitis Symptom Index in a prospective longitudinal inception cohort study. RESULTS: On average symptoms improved substantially during months 1 to 3, modestly from months 3 to 6 and then remained unchanged. At each followup outcomes were better for men whose initial visit was for a first lifetime episode compared with a recurrent prostatitis/pelvic pain episode. Patients with more severe symptoms (Wald chi-square 11.27, p = 0.0008) and whose episode was recurrent (OR 2.2, 95% CI 1.16 to 4.06) at baseline were significantly more likely to report symptoms 1 year later. CONCLUSIONS: Most men who make physician visits for new nonbacterial prostatitis/pelvic pain episodes experience symptom improvement during the next 6 months. However, chronic, mild, persistent or recurrent symptoms are common. Patients with previous episodes and more severe symptoms are at higher risk for chronic pelvic pain.     

Terazosin therapy for chronic prostatitis/chronic pelvic pain syndrome: a randomized,placebo controlled trial

PURPOSE: We evaluate terazosin therapy for chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: The study included 100, 20 to-50-year-old subjects who met the consensus criteria for chronic prostatitis/chronic pelvic pain syndrome and had not received previous alpha-blockers. Subjects were randomized to receive terazosin with dose escalation from 1 to 5 mg. daily or placebo for 14 weeks. The primary criterion for response was scoring 2 or less ("delighted-to-mostly satisfied") on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) quality of life item. The secondary criterion for response was greater than 50% reduction in NIH-CPSI pain score at 14 weeks. Other outcomes included total and NIH-CPSI domain scores, International Prostate Symptom Score, peak urinary flow rate, post-void residual urine and adverse effects. RESULTS: Using the primary criterion 24 of 43 evaluable subjects (56%) responded in the terazosin group compared to 14 of 43 (36%) in the placebo group (p = 0.03). Using the secondary criterion 26 of 43 subjects (60%) responded in the terazosin group compared to 16 of 43 (37%) in the placebo group (p = 0.03). The terazosin group had greater reductions (p <0.05) in NIH-CPSI total score, individual domain scores and International Prostate Symptom Score than the placebo group. There was no difference in peak urinary flow rate or post-void residual. In the terazosin group 18 patients (42%) had side effects compared to 9 (21%) in the placebo group (p = 0.04). CONCLUSIONS: Terazosin proved superior to placebo for patients with chronic prostatitis/chronic pelvic pain syndrome who had not received alpha-blockers previously.     

Treatment of chronic prostatitis/chronic pelvic pain syndrome with tamsulosin: a randomized double blind trial

PURPOSE: We compared the efficacy of tamsulosin with placebo for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). MATERIALS AND METHODS: In a double blind phase II trial, 58 patients 55 years old or younger with moderate to severe CP/CPPS were randomized to receive 0.4 mg tamsulosin or placebo for 6 weeks. Patients were assessed on days -14 and -1 during a 2-week washout, and on days 15 and 45. The primary end point was the change from baseline in total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score on day 45. Secondary end points were the change from baseline in total NIH-CPSI score on day 15 and the change from baseline in pain, urinary symptoms and quality of life/impact domains of the NIH-CPSI on days 15 and 45. Analyses of responders were performed post hoc. RESULTS: On day 45 the treatment effect (difference between treatment groups in change from baseline) was -3.6 (p = 0.04) in favor of tamsulosin. The overall effect of tamsulosin was a function of the baseline total NIH-CPSI score. Treatment effect increased significantly as the baseline score increased (for total NIH-CPSI p <0.01). Tamsulosin efficacy was superior to placebo at the 75th percentile of baseline score for the total NIH-CPSI score (-8.3, p <0.01), the pain domain (-2.9, p = 0.02), the urinary symptoms domain (-2.3, p <0.01) and the impact/quality of life domain (-2.1, p = 0.02). The efficacy of tamsulosin increased with time (no significant treatment difference at 15 days) and tamsulosin was well tolerated. CONCLUSIONS: Tamsulosin was superior to placebo in providing symptomatic relief in men with CP/CPPS, particularly in those with more severe symptoms.     

Cryotherapy alleviates symptoms in chronic prostatitis/chronic pelvic pain syndrome: The first results

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an intractable disease. This study aimed to assess the efficacy of cryotherapy in the therapy of CP/CPPS. One hundred and seventy-two patients with CP/CPPS were randomised to receive cryotherapy or sham cryotherapy. The follow-up assessments were done at weeks 4, 12 and 24 using Visual Analogue Scale (VAS), International Prostate Symptom Score (IPSS) and National Institutes of Health-developed Chronic Prostatitis Symptom Index. The per-protocol analysis was performed. Eighty-two patients in the cryotherapy group and 76 patients in the sham group completed the treatment. The most obvious improvement (67%) of the VAS was observed in the cryotherapy group after 4 weeks, and although the improvement slightly weakened by 24 weeks (62.6%), a significant improvement from the treatment remained apparent. IPSS improved by 75% after 4 weeks and remained stable after 24 weeks. The response rates were 78.0%, 73.2% and 70.1% at weeks 4, 12 and 24 in the cryotherapy group, which were higher than 17.1%, 13.2% and 10.5% in the sham group (each p < .001). These results indicated that cryotherapy could alleviate voiding symptoms, ameliorate pain and improve the quality of life in people with CP/CPPS. It holds promise as a novel strategy to treat CP/CPPS.     

生物反馈和电刺激联合治疗慢性前列腺炎/慢性骨盆疼痛综合征

目的:通过临床试验的方法,探讨生物反馈和电刺激联合治疗慢性前列腺炎/慢性骨盆疼痛综合征(CP/CPPS)的效果。方法:收集湘雅医院门诊诊断为CP/CPPS符合研究标准患者140例。将患者随机分为对照组、生物反馈组、电刺激组和生物反馈加电刺激组;对照组20例,生物反馈组、电刺激组和生物反馈加电刺激组各40例。采用Laborie-Urostym生物反馈电刺激治疗仪,生物反馈组行生物反馈治疗,电刺激组行电刺激治疗,生物反馈加电刺激组行生物反馈电刺激治疗;每周5次,连续2周;对照组不予上述治疗,随诊1个月。治疗前后进行NIH-CPSI评分以及尿流率检查。结果:生物反馈组、电刺激组和生物反馈加电刺激组治疗后NIH-CPSI疼痛与不适评分、NIH-CPSI排尿症状评分、NIH-CPSI生活质量评分、NIH-CPSI总评分、最大尿流率较治疗前均有显著改善(P<0.05);治疗前各组积分及最大尿流率比较无显著差异(P>0.05);治疗后上述参数生物反馈组、电刺激组比较没有显著差异(P>0.05),生物反馈加电刺激组与生物反馈组、电刺激组比较有显著差异(P<0.05)。而对照组治疗前后的以上各组评分及最大尿流率比较无显著差异(P>0.05)。结论:生物反馈和电刺激治疗能明显改善CP/CPPS患者疼痛与不适症状,排尿症状,提高生活质量,以及提高最大尿流率。生物反馈和电刺激联合治疗CP/CPPS有协同作用。     

氯美扎酮联合吲哚美辛栓治疗慢性非细菌性前列腺炎／慢性盆腔疼痛综合征的研究

目的评价氯美扎酮联合吲哚美辛栓治疗以疼痛为主诉的慢性非细菌性前列腺炎／慢性盆腔疼痛综合征（CP／CPPS）的疗效。方法对符合CP／CPPS标准的180例患者随机分为吲哚美辛栓组、氯美扎酮联合吲哚美辛栓组及特拉唑嗪组,疗程4周。在治疗结束时进行疗效判定,疗效评价标准采用视觉模拟评分方法。结果中途退出7例,173例患者进行了疗效评价,联合治疗组症状改善总有效率与吲哚美辛栓组（x^2=3．87,P〈0．05）和特拉唑嗪组（x^2=6．82,P〈0．01）相比疗效差异有统计学意义。治疗过程中无严重不良反应发生。结论氯美扎酮联合吲哚美辛栓可作为CP／CPPS疼痛患者的一种有效治疗手段。     

Quercetin for chronic prostatitis/chronic pelvic pain syndrome

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition with a heterogeneous origin that responds best to multimodal therapy. The bioflavonoid quercetin has antioxidant and antiinflammatory effects that have proven useful for treating this condition. Using the clinical phenotype system UPOINT, quercetin can be helpful for those with organ-specific complaints (bladder or prostate) and pelvic floor spasm. This article discusses the current understanding of CP/CPPS and how treatment with quercetin can be used alone or as part of multimodal therapy.     

Significance of inflammation on standard semen analysis in chronic prostatitis/chronic pelvic pain syndrome

The impact of defined urogenital inflammations on standard ejaculate parameters is still a matter of controversial debate. Basic spermiogram parameters has been analysed in patients with inflammatory and noninflammatory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-NIH IIIA/IIIB) with regard to indicators of inflammation in prostatic secretions and/or the ejaculate. A total of 112 consecutive patients symptomatic for chronic pelvic pain were included in the study. All of them underwent a 'four glass-test' including leukocyte determination in expressed prostatic secretions followed by ejaculate analysis according to WHO. The analysis included pH, volume, total sperm count, sperm density, motility, morphology (Shorr stain), vitality (eosin stain), and counting of peroxidase positive leukocytes (PPL). Patients were first subgrouped according to elevated leukocyte counts in prostatic secretions, and then according to the number of PPL in semen. Leukocytes neither in the prostatic secretions nor in the ejaculate were associated with reduced standard semen parameters. Our data supports previous results that elevated leukocyte counts in prostatic secretions and in ejaculate, as indicators of inflammation have no negative impact on total sperm count, sperm density, motility, morphology, and sperm vitality in patients with CP/CPPS.