Low-intensity shockwave therapy in men’s health: Insights from a systematic review on erectile dysfunction and CP/CPPS in the Middle East

Low-Intensity Shock Wave Therapy in Sexual Medicine—Clinical Recommendations from the European Society of Sexual Medicine (ESSM)

To perform a systematic review and meta-analysis aiming to improve the level of evidence and determine the efficacy and safety of low-intensity shockwave therapy (LiST) in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We searched PubMed, Cochrane Library and Scopus databases from inception to November 2020 for randomised controlled trials (RCTs) exploring the role of LiST for the management of CP/CPPS. We performed a random-effects meta-analysis of RCTs comparing LiST vs sham therapy on CP/CPPS symptoms at different time-points after treatment. Weighted mean differences (WMDs) with the corresponding confidence intervals (CIs) were estimated. Furthermore, we assessed the strength of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42020208813). We included five sham RCTs and one non-sham RCT. In the meta-analysis of sham RCTs, both the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) pain domain score and the numeric pain rating scale improved significantly after LiST vs sham therapy at the assessment directly after treatment protocol completion (WMD 3.2, 95% CI 0.88-5.52, I2 = 90%; and WMD 1.43, 95% CI 0.85-2.01, I2 = 32%, respectively), at 1month (WMD 4.4, 95% CI 2.84-5.95, I2 = 68%, and WMD 2.59, 95% CI 1.92-3.27, I2 = 83%, respectively), and at 3months after last treatment session (WMD 3.61, 95% CI 1.49-5.74, I2 = 90%, and WMD 2.64, 95% CI 2.13-3.16, I2 = 71%, respectively). Similarly, the NIH-CPSI total and quality-of-life domain scores improved significantly after LiST compared to sham therapy for the same time-points. Conversely, the long-term efficacy of LiST, as well as the effect of LiST on lower urinary tract symptoms and erectile function, was clinically insignificant. LiST is an effective treatment modality for the improvement of pain and quality of life in patients with CP/CPPS. Therefore, it should be recommended as a part of individualised treatment strategies in such patients.

Use of the UPOINT Chronic Prostatitis/Chronic Pelvic Pain Syndrome Classification in European Patient Cohorts: Sexual Function Domain Improves Correlations

Introduction:In this study, the efficacy of low intensity shock wave therapy (LSWT) in improving symptoms of chronic pelvic pain syndrome (CPPS) and erectile dysfunction (ED) was investigated.Methods:Men diagnosed with CPPS and ED (n = 50) were prescribed with LSWT. The LSWT was administered in 10 sessions over the course of 5 weeks at 3,000 pulses with .25 mJ/mm2 energy flow and 5 Hz frequency. Outcome parameters were measured before and after LSWT.Results:Clinical symptoms related to CPPS and ED were measured using four validated questionnaires namely National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Index of Erectile Function (IIEF), the International Prostate Symptom Score (IPSS), and Sexual Health Inventory for Men (SHIM). The effect of LSWT on each of the three domains of NIH-CPSI, namely Pain, Symptoms, and Quality of Life (QoL) were also analyzed. Uroflowmetry was measured to assess LSWT effect on urine voiding. The mean baseline CPPS symptoms on NIH-CPSI domains of pain, symptoms and QoL were 9.92 ± 5.72 (mean ± SD), 5.14 ± 14.5, and 8.02 ± 3.17, respectively. LSWT resulted in significant reduction of CPPS symptoms on all NIH-CPSI domains (Pain = .9 ± 1.37; Symptoms = .74 ± 1.03; QoL = 1.16 ± 1.78). The baseline means of CPPS symptoms on IIEF, IPSS, and SHIM were 45.42 ± 16.24, 24.68 ± 9.28, and 14.28 ± 6.02, respectively. LSWT significant improved CPPS symptoms on IIEF (49.48 ± 28.30) and IPSS (9.04 ± 7.01) but not on SHIM (16.02 ± 9.85). No statistically significant differences were observed with all uroflowmetry parameters.Conclusion:The current study demonstrated for the first time the safety and efficacy of LSWT administered in 10 sessions over 5 weeks in improving symptoms of CPPS and ED without causing any significant adverse effect to the patient.

This study aimed to assess the association between psychological disorders and erectile dysfunction (ED) in patients with different degrees of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This was a retrospective study conducted from June 2017 to October 2019 and included 182 outpatients. Patients were interviewed using the Structured Interview on Erectile Dysfunction (SIEDY) for pathogenic quantification. The National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Index of Erectile Function-5 (IIEF-5) were used for the evaluation of CP/CPPS and ED. The Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to assess anxiety symptoms and depressive symptoms. The number of patients with mild CP/CPPS and mild ED, mild CP/CPPS and moderate-to-severe ED, moderate-to-severe CP/CPPS and mild ED, and moderate-to-severe CP/CPPS and moderate-to-severe ED was 69 (37.9%), 36 (19.8%), 35 (19.2%), and 42 (23.1%), respectively. The corresponding PHQ-9 scores of the four groups were 6.22, 7.19, 10.69, and 7.71, respectively. The corresponding GAD-7 scores of the four groups were 5.26, 6.31, 8.77, and 6.36, respectively. Among patients with moderate-to-severe CP/CPPS, the PHQ-9 and GAD-7 scores of the moderate-to-severe ED group were significantly lower than those of the mild ED group (P = 0.007 and P = 0.010, respectively). The prevalence of ED and premature ejaculation (PE) in patients with moderate-to-severe CP/CPPS was significantly higher than that in patients with mild CP/CPPS (P = 0.001 and P = 0.024, respectively). Our findings proved that the severity of ED was negatively associated with psychological symptoms in outpatients with moderate-to-severe CP/CPPS.

6-Day Intensive Treatment Protocol for Refractory Chronic Prostatitis/Chronic Pelvic Pain Syndrome Using Myofascial Release and Paradoxical Relaxation Training

Mental stress and imbalance of its two neural stress systems, the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis, are associated with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED). However, the comprehensive analyses of psychological stress and stress systems are under-investigated, particularly in CP/CPPS patients complicated by lower urinary tract symptoms (LUTS) and ED. Participants were 95 patients in CP/CPPS+ED group, 290 patients in CP/CPPS group, 124 patients in ED group and 52 healthy men in control group. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Index of Erectile Function-5 (IIEF-5) and the International Prostate Symptom Score (IPSS) were used for assessing the disease severity of CP/CPPS, LUTS and ED. Psychometric self-report questionnaires including the Beck Anxiety Inventory (BAI), Perceived Stress Scale (PSS), Type A Personality Test (TAPT) and Symptom Checklist 90 (SCL-90) were completed for distress from physical symptoms. Twenty-five subjects per group were randomly selected for further investigating the changes of the HPA axis and ANS. Saliva samples were taken on 3 consecutive days at 8 specific times with strict reference to time of morning awakening for evaluation of free cortisol. Heart rate variability (HRV) as marker of the ANS was measured using 24 h electrocardiography, and time-and frequency-domain variables were analyzed. The BAI and SCL-90 scores were significantly higher in the CP/CPPS+ED, CP/CPPS and ED groups compared with the control group (p < 0.01). The PSS scores of both groups with ED were significantly higher than the control group (p < 0.01). Compared with the CP/CPPS group, the differences of PSS, SCL-90 and TAPT scores were statistically significant in CP/CPPS+ED patients (p < 0.01). The IPSS scores were shown to have significantly positive correlations with BAI (r = 0.32, p < 0.0001), PSS (r = 0.18, p < 0.01) and SCL-90 (r = 0.19, p < 0.01) in the CP/CPPS patients. However, in all subjects, the IIEF-5 scores were shown to have significantly negative correlations with BAI (r = -0.17，p < 0.001), PSS (r = -0.25，p < 0.0001), SCL-90 (r = -0.20，p < 0.001) and quality of life score in NIH-CPSI (r = -0.14，p = 0.0075). Cortisol awakening response (CAR) parameters and diurnal cortisol levels did not significantly vary between the four groups. Time-dependent parameters of HRV also did not differ significantly across groups. In the frequency domain analysis, low frequency (LF) was significantly lower in ED patients when compared with CP/CPPS+ED patients (p = 0.044) and healthy controls (p = 0.005), high frequency (HF) power was significantly higher in healthy controls compared to patients with ED (p < 0.001), CP/CPPS (p < 0.001) and CP/CPPS+ED (p < 0.001), and the CP/CPPS+ED group had significantly higher LF/HF ratio than the control group (p = 0.001). CP/CPPS and ED patients score exceedingly high on most psychosocial variables. The symptom scores of LUTS and ED positively correlate with the severity of psychological stress. Our findings also suggest that the ANS sympathovagal imbalance is associated with ED and LUTS in CP/CPPS, whereas HPA axis activity is not.

What's known on the subject? and What does the study add? In recent years, a number of studies have reported a high prevalence of erectile dysfunction (ED) among patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Several studies have reported that the prevalence of ED ranges from 15.0 to 40.5% in men in China with CP/CPPS; however, the previous studies focusing on the prevalence of ED among patients with CP/CPPS all neglected to explore the magnitude of this association. Our study found an association between ED and previously diagnosed CP/CPPS. The odds of previous CP/CPPS were 3.62 times greater for cases than for controls, after adjusting for patient socio-demographic characteristics, comorbidities, obesity, and alcohol abuse/alcohol dependence syndrome. To examine the association between erectile dysfunction (ED) and a previous diagnosis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using a population-based dataset. The data for this case-control study was obtained from the National Health Insurance database. A total of 3194 males, who were ≥18 years of age when they first received a diagnosis of ED, were identified and 15 970 controls were randomly selected. The prevalence and risk of CP/CPPS among cases and controls were calculated by using conditional logistic regression analysis. In total, 667 (3.5%) of the 19 164 sampled subjects had been diagnosed with CP/CPPS before the index date; CP/CPPS was found in 276 (8.6%) cases and in 391 (2.5%) controls (P < 0.001). Regression analysis indicated that cases were more likely to have had previous CP/CPPS (odd ratio 3.62, 95% confidence interval 3.07-4.26) after adjusting for patient monthly income, geographical location and urbanization level, as well as hypertension, diabetes, coronary heart disease, renal disease, obesity and alcohol abuse/alcohol dependence syndrome status, when compared with controls. We conclude that there was an association between ED and having been previously diagnosed with CP/CPPS. Urologists should be alert to the association between CP/CPPS and ED, and assess the erectile function of patients suffering from CP/CPPS.

1154 ASSOCIATION BETWEEN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME AND ERECTILE DYSFUNCTION A POPULATION-BASED STUDY

Despite encouraging results, the optimal low-intensity shockwave therapy (LiST) protocol in patients with chronic prostatitis/chronic pelvic pain syndrome (CPPS) remains unknown. We conducted a two-arm, parallel-group, randomized controlled trial aiming to compare the efficacy and safety of six LiST sessions applied once or twice weekly. Fifty patients with CP/CPPS type IIIb were randomly assigned to six LiST sessions once (Group A, n = 25) or twice weekly (Group B, n = 25). Both groups followed the same treatment protocol in terms of LiST application, impulses (5000/session), energy flux density (0.096 mJ/mm2 ) and frequency (5 Hz). Subsequently, all participants were evaluated at 1 and 3 months after completion of LiST protocol. At the follow-up evaluations, LiST significantly improved the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) total, pain and quality of life scores, as well as the International Index of Erectile Function-Erectile Domain (IIEF-ED) in both groups (p < .001 for all measures). Comparing between the two groups, no significant differences were demonstrated in the NIH-CPSI total, pain, urinary and quality of life scores, as well as in the International Prostate Symptom Score, IIEF-ED, and LiST-induced pain at both follow-up evaluations. Accordingly, no adverse events and no dropouts were observed in both groups. Six sessions of LiST applied once weekly for 6 weeks or twice weekly for 3 weeks seem to be equally safe and effective in patients with CP/CPPS. Nevertheless, further studies are necessary, since LiST gradually gains its place for the management of CP/CPPS.

Background: Clinical associations between erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been noticed, but the common pathogenic mechanisms between them remain elusive. The aim of the study was to mine shared genetic alterations between ED and chronic prostatitis/chronic pelvic pain syndrome. Method: Transcriptome data of ED and chronic prostatitis/chronic pelvic pain syndrome-related genes (CPRGs) were retrieved from relevant databases and differentially expressed analysis was used to obtain significant CPRGs. Then function enrichment and interaction analyses were performed to show shared transcriptional signature, including gene ontology and pathway enrichment, the construction of protein-protein interaction (PPI) network, cluster analysis, and co-expression analysis. Hub CPRGs and key cross-link were selected by validating these genes in clinical samples, chronic prostatitis/chronic pelvic pain syndrome and ED-related datasets. Then the miRNA-OSRGs co-regulatory network was predicted and validated. Subpopulation distribution and disease association of hub CPRGs were further identified. Result: Differentially expressed analysis revealed 363 significant CPRGs between ED and chronic prostatitis/chronic pelvic pain syndrome, functioning in inflammatory reaction, oxidative stress, apoptosis, smooth muscle cell proliferation, and extracellular matrix organization. A PPI network containing 245 nodes and 504 interactions was constructed. Module analysis depicted that multicellular organismal process and immune metabolic process were enriched. 17 genes were screened in PPI via topological algorithms, and reactive oxygen species as well as interleukin-1 metabolism were regarded as the bridging interactive mechanism. After screening and validation, a hub-CPRG signature consisting of COL1A1, MAPK6, LPL, NFE2L2 and NQO1 were identified and associated miRNA were verified. These miRNAs played an important role in immune and inflammatory response likewise. Finally, NQO1 was identified as a key genetic link between ED and chronic prostatitis/chronic pelvic pain syndrome. It was predominately enriched in corpus cavernosum endothelial cell, and correlated with other male urogenital and immune system diseases tightly. Conclusion: We identified the genetic profiles as well as corresponding regulatory network underlying interaction between ED and chronic prostatitis/chronic pelvic pain syndrome via multi-omics analysis. These findings expanded a new understanding for the molecular mechanism of ED with chronic prostatitis/chronic pelvic pain syndrome.

PD62-03 CASE SERIES OF LOW INTENSITY SHOCK WAVE THERAPY FOR MEN WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME

BackgroundHigh prevalence of erectile dysfunction (ED) has been observed in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, whether or not CP/CPPS is a risk factor of ED remains unknown and controversial. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between CP/CPPS and ED.MethodsPubMed, Embase, Web of Science, and The Cochrane Library were searched up to November 11, 2014 to identify studies reporting the association between CP/CPPS and ED. Case–control, cohort and cross-sectional studies were included. Quality of the included studies was assessed. The odds ratio of ED and the mean difference of five-item International Index of Erectile Function (IIEF-5) score were pooled using a random effects model. Subgroup analysis and sensitivity analyses were performed.ResultsThree cross-sectional studies, two case–control studies, and four retrospective studies with 31,956 participants were included to calculate the pooled odds ratio of ED, and two studies with 1499 participants were included to calculate the pooled mean difference of IIEF-5 scores. A strong correlation was found between CP/CPPS and ED (pooled odds ratio: 3.02, 95% CI: 2.18–4.17, P < 0.01), with heterogeneity across studies (I 2 = 65%; P < 0.01). A significant decrease in the IIFE-5 score was observed in the CP/CPPS group (pooled mean difference: −4.54, 95% CI: −5.11–−3.98; P < 0.01).ConclusionOur study indicates that patients with CP/CPPS have an increased risk of suffering from ED. Assessment of erectile function is necessary for the therapy of patients with CP/CPPS. Further evidence is necessary to confirm the relationship between CP/CPPS and ED.

BackgroundRecent data showed that a six-domain UPOINT is a flexible and responsive new classification system that has the clinical applicability in CP/CPPS. However, the utility of UPOINT algorithm in men in China with CP/CPPS has not been comprehensively studied. For international validation and adoption, we evaluated this clinical phenotype system for a large cohort of Chinese CP/CPPS patients and correlated it with patient symptoms and erectile dysfunction (ED). We also investigated the addition of an ED domain in regard to symptom correlation.MethodsA total of 389 Chinese males with CP/CPPS were prospectively collected and classified in each domain of the UPOINT system. Symptom severity was measured using the NIH-CPSI and IPSS. The erectile function was evaluated using the IIEF-5. Clinically relevant associations were calculated.ResultsThe percentage of patients positive for each domain was 54.0%, 42.1%, 41.9%, 20.8%, 26.7%, and 40.4% for the Urinary, Psychosocial, Organ-specific, Infection, Neurological/systemic, and Tenderness, respectively. There were significant correlations between the number of positive UPOINT domains and total NIH-CPSI (r = 0.706, p<0.001), IPSS (r = 0.682, p<0.001) and IIEF-5 scores (r = 0.631, P = 0.007) in Chinese cohort. Except for patients age, symptom duration was associated with a significantly greater number of positive domains (r = 0.638, P = 0.005). After adding an ED domain to create a modified UPOINT system, the correlation between the number of phenotypic domains and symptom severity was improved (0.706 to 0.844, p<0.001).ConclusionsThe clinical applicability of using UPOINT phenotyping system has been validated in the Chinese patients with CP/CPPS. In our cohort, the number of positive domains was also correlated with ED symptoms and the significant association between the number of UPOINT domains and NIH-CPSI scores was further refined by adding a domain for ED. Our findings presented here support the utility of using ED as a stand-alone item in the UPOINT domain.

1173 ETIOLOGIC EVALUATION OF ERECTILE DYSFUNCTION IN MEN WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME