The effect of combination treatment with low-intensity shockwave therapy and daily tadalafil on severe erectile dysfunction: a double-blind, randomized, sham-controlled clinical trial.

BACKGROUND: Patients with severe erectile dysfunction (ED) remain the most challenging group in terms of available noninvasive treatment modalities. AIM: The study sought to assess the role of combination therapy with low-intensity shockwave therapy (LiST) and daily tadalafil 5 mg in a highly select group of patients with severe vasculogenic ED through a double-blind, randomized trial. METHODS: Forty-eight sexually active men were randomly assigned to 12 sessions of LiST 3 times weekly and tadalafil 5 mg once daily (n = 34) or sham therapy and tadalafil (n = 17) for 4 weeks. Patients were assessed at 1 and 3 months after completion of treatment. OUTCOMES: Improvement of erectile function was evaluated through the International Index of Erectile Function-Erectile Function domain (IIEF-EF) or 6-item IIEF and the Sexual Encounter Profile (SEP) diary. The primary outcome was the difference between the groups in the IIEF-EF at 3 months after completion of treatment. Secondary outcomes comprised (1) the difference between the groups in the IIEF-EF at 1 month after completion of treatment, (2) the difference between the groups in the "yes" responses to question 3 of the SEP diary at 1 and 3 months, and (3) the treatment-related adverse events. The number of patients attaining a minimal clinically important difference in the IIEF-EF (improvement of at least 7 points) was also assessed. RESULTS: After treatment, the absolute scores in the IIEF-EF were higher in patients receiving LiST and tadalafil vs sham therapy and tadalafil both at the 1-month (12.1 ± 2.4 vs 10.2 ± 1.7; P = .002) and at the 3-month (12.9 ± 2.1 vs 10.8 ± 1.8; P < .001) evaluation. Between the 2 groups, the proportion of "yes" responses to question 3 of the SEP diary was not statistically significant, whereas the number of patients attaining a minimal clinically important difference in the IIEF-EF was statistically significant only at the 3-month evaluation. No adverse events occurred. CLINICAL IMPLICATIONS: Application of LiST in patients with severe vasculogenic ED receiving daily dose tadalafil may further improve erectile function compared with tadalafil as a stand-alone treatment on the short term. STRENGTHS AND LIMITATIONS: Although we provided the first study in the field, severe vasculogenic ED was defined based on medical history and clinical examination and not based on penile ultrasound measures. CONCLUSION: The combination of 12 sessions LiST 3 times weekly and daily tadalafil for 4 weeks led to a 2-point difference in the IIEF-EF compared with sham therapy and daily tadalafil among patients with severe vasculogenic ED after 1 and 3 months from completion of treatment.

The Effect of Low-Intensity Shock Wave Therapy on Moderate Erectile Dysfunction: A Double-Blind, Randomized, Sham-Controlled Clinical Trial.

PURPOSE: We conducted the first double-blind, randomized, sham-controlled trial evaluating the efficacy and safety of low-intensity shock wave therapy (LiST) exclusively in patients with moderate erectile dysfunction. MATERIALS AND METHODS: Seventy patients were randomized to 12 sessions of LiST (35) or sham therapy (35) twice weekly. Patients were evaluated at 1 and 3 months after completion of treatment. The proportion of participants attaining minimal clinically important difference (MCID) in the International Index of Erectile Function-Erectile Function (IIEF-EF) and the effect of LiST on erectile function, as well as on safety, were the study outcomes. RESULTS: At 3 months, MCID was attained by 27 (79%) patients in the LiST group compared to 0 patients in the sham group. The risk difference between the 2 groups was 79% (95% confidence interval [CI]: 66-93, p <0.001) and the baseline-adjusted mean between-group-difference in the IIEF-EF was 4.4 points (95% CI: 3.4-5.4, p <0.001). At 1 month, MCID was attained by 20 (59%) patients in the LiST group compared to 1 (2.9%) patient in the sham group. The risk difference between the 2 groups was 56% (95% CI: 38-73, p <0.001) and the baseline-adjusted mean between-group-difference in the IIEF-EF was 3.9 points (95% CI: 2.7-5.2, p <0.001). CONCLUSIONS: Twelve sessions of LiST twice weekly for 6 weeks with a treatment protocol of 5,000 impulses, 0.096 mJ/mm2 energy flux density and 5 Hz frequency are highly effective in patients with moderate erectile dysfunction. Still, further long-term randomized studies are warranted to corroborate our findings.

The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Combination of different first-line treatments for erectile dysfunction (ED) has emerged as a promising therapeutic approach. AIM: To conduct the first double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy and safety of combination therapy with low-intensity shockwave therapy (LiST) and tadalafil vs LiST and placebo in patients with mild or mild-to-moderate vasculogenic ED. METHODS: Fifty sexually active patients fulfilling the eligibility criteria were randomly assigned to 6 sessions of LiST twice weekly for 3 weeks and tadalafil (n = 25) or placebo (n = 25) once daily for 4 weeks. Patients were evaluated at 1, 3, and 6 months after completion of the treatment protocol. OUTCOMES: The primary outcome was the mean change from baseline in the International Index of Erectile Function-Erectile Function (IIEF-EF) domain between the 2 groups at 3 months after treatment. Erectile function was also assessed at 1 and 6 months. The number of patients attaining a minimal clinically important difference (MCID) in the IIEF-EF, as well as the safety of combination therapy were evaluated. RESULTS: Adjusting for the baseline values, IIEF-EF improved by 0.8 points more (95% confidence interval [CI] = -0.2 to 1.9, P = .12) at 1 month, 1 point more (95% CI = 0.1-1.9, P = .02) at 3 months and 1.7 points more (95% CI = 0.8-2.7, P < .001) at 6 months in patients treated with combination therapy compared to monotherapy. The number of patients attaining a MCID in the IIEF-EF between the 2 groups improved significantly only at the 3-month evaluation. No adverse events were reported during the whole study period. CLINICAL IMPLICATIONS: Combination of LiST twice weekly for 3 weeks and tadalafil 5 mg once daily for 4 weeks may further ameliorate mild or mild-to-moderate vasculogenic ED compared to LiST monotherapy. STRENGTHS & LIMITATIONS: We conducted the first randomized trial exploring the role of LiST and tadalafil in the management of ED. Conversely, our study lacks external validity due to its single-center design. CONCLUSION: The addition of daily low-dose tadalafil during application of LiST may further improve erectile function compared to application of LiST as a standalone treatment in patients with mild or mild-to-moderate vasculogenic ED. Still, further high-quality studies are warranted to corroborate our findings. Mykoniatis I, Pyrgidis N, Zilotis F, et al. The Effect of Combination Treatment With Low-Intensity Shockwave Therapy and Tadalafil on Mild and Mild-To-Moderate Erectile Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med 2022;19:106-115.

Comparing two different low-intensity shockwave therapy frequency protocols for nonbacterial chronic prostatitis/chronic pelvic pain syndrome: A two-arm, parallel-group randomized controlled trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Does Ureteral Stenting Increase the Risk of Metachronous Upper Tract Urothelial Carcinoma in Patients with Bladder Tumors? A Systematic Review and Meta-analysis.

PURPOSE: Ureteral stenting in patients with bladder cancer may become necessary in order to protect the ureteral orifice during transurethral resection of the tumor or for relief of upper urinary tract obstruction. However, it is believed to increase metachronous upper tract urothelial carcinoma risk. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of studies comparing ureteral stenting versus nephrostomy or no drainage with regard to the risk of metachronous upper tract urothelial carcinoma. Records were identified through database searches and sources of grey literature up to October 2020 (PROSPERO: CRD42020178298). RESULTS: Five studies (3,309 individuals) were included. Overall, 278 ureteral stents were placed and 20 (7.2%) patients developed metachronous upper tract urothelial carcinoma, while 131 patients were treated with nephrostomy and 3 (2.3%) cases of metachronous upper tract urothelial carcinoma occurred. Patients treated with ureteral stents had a higher likelihood of metachronous upper tract urothelial carcinoma compared to no stents (OR: 3.49, 95% CI: 1.43-8.48, I2=52%) and no upper urinary tract drainage (OR: 3.37, 95% CI: 1.49-7.63, I2=45%). No difference with regard to metachronous upper tract urothelial carcinoma was observed between stent and nephrostomy (OR: 3.07, 95% CI: 0.41-22.98, I2=54%). For the same outcomes, no difference was noted for patients with hydronephrosis. The level of evidence for all measures was evaluated as low. CONCLUSIONS: Stenting as a preventive measure after resection of tumors involving the orifice should be avoided, when possible, as it increases the risk of metachronous upper tract urothelial carcinoma. In cases of hydronephrosis, drainage with either nephrostomy or stent is recommended depending on individual patient cases as both interventions do not differ regarding metachronous upper tract urothelial carcinoma risk.

Renal Transplantation Improves Erectile Function in Patients with End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

PURPOSE: Erectile dysfunction has a lower prevalence in renal transplant recipients compared to dialysis patients. Despite this observation, the effect of renal transplantation on erectile function remains unknown. We aimed to assess the role of renal transplantation on erectile function and to determine potential factors improving or deteriorating erectile dysfunction. MATERIALS AND METHODS: We conducted a systematic review and random effects meta-analysis of observational studies comparing erectile function preoperatively and postoperatively in renal transplant recipients (PROSPERO ID: CRD42020189580). Records reporting relevant outcomes were identified through search of PubMed®, Embase®, Cochrane Library and Scopus® databases from inception to September 2020. Judgment of the strength of evidence was performed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included 20 studies with 1,695 renal transplant recipients. At postoperative evaluation the number of patients with erectile dysfunction was reduced (RR 1.21, 95% CI 1.02-1.45, I2=88%). Renal transplant recipients reported an improvement in erectile function (RR 2.53, 95% CI 1.44-4.44, I2=90%) and the mean International Index of Erectile Function score increased by 3.04 points (95% CI 0.63-5.45, I2=96%) after renal transplantation. These effects were not demonstrated in the sensitivity analysis. In individuals reporting severe erectile dysfunction, no favorable effect of renal transplantation was observed (RR 1.51, 95% CI 0.85-2.68, I2=33%). For all outcomes the strength of evidence was considered low or very low due to methodological concerns and high heterogeneity among the included studies. CONCLUSIONS: Renal transplantation improves erectile function and the risk of erectile dysfunction reduces postoperatively compared to preoperatively. However, evidence on the matter is mostly based on low quality data. More studies with standardized outcomes are needed to validate and strengthen our findings.

Micro-Ultrasound-Guided vs Multiparametric Magnetic Resonance Imaging-Targeted Biopsy in the Detection of Prostate Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Micro-ultrasound is a novel high resolution ultrasound technology aiming to improve prostate imaging and, consequently, the diagnostic accuracy of ultrasound-guided prostate biopsy. Micro-ultrasound-guided prostate biopsy may present comparable detection rates to the standard of care multiparametric magnetic resonance imaging-targeted prostate biopsy for the diagnosis of clinically significant prostate cancer. We aimed to compare the detection rate of micro-ultrasound vs multiparametric magnetic resonance imaging-targeted prostate biopsy for prostate cancer diagnosis. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of diagnostic accuracy studies comparing micro-ultrasound-guided prostate biopsy to multiparametric magnetic resonance imaging-targeted prostate biopsy as a reference standard test (PROSPERO ID: CRD42020198326). Records were identified by searching in PubMed®, Scopus® and Cochrane Library databases, as well as in potential sources of gray literature until November 30th, 2020. RESULTS: We included 18 studies in the qualitative and 13 in the quantitative synthesis. In the quantitative synthesis, 1,125 participants received micro-ultrasound-guided followed by multiparametric magnetic resonance imaging-targeted and systematic prostate biopsy. Micro-ultrasound and multiparametric magnetic resonance imaging-targeted prostate biopsies displayed similar detection rates across all prostate cancer grades. The pooled detection ratio for International Society of Urological Pathology Grade Group ≥2 prostate cancer was 1.05 (95% CI 0.93-1.19, I2=0%), 1.25 (95% CI 0.95-1.64, I2=0%) for Grade Group ≥3 and 0.94 (95% CI 0.73-1.22, I2=0%) for clinically insignificant (Grade Group 1) prostate cancer. The overall detection ratio for prostate cancer was 0.99 (95% CI 0.89-1.11, I2=0%). CONCLUSIONS: Micro-ultrasound-guided prostate biopsy provides comparable detection rates for prostate cancer diagnosis with the multiparametric magnetic resonance imaging-guided prostate biopsy. Therefore, it could be considered as an attractive alternative to multiparametric magnetic resonance imaging-targeted prostate biopsy. Nevertheless, high quality randomized trials are warranted to corroborate our findings.

Low-intensity shockwave therapy for the management of chronic prostatitis/chronic pelvic pain syndrome: a systematic review and meta-analysis.

OBJECTIVES: 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). METHODS: 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). RESULTS: 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 1 month (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 3 months 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. CONCLUSIONS: 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.

Platelet-Rich Plasma (PRP) Improves Erectile Function: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial.

BACKGROUND: Animal studies postulate that platelet-rich plasma (PRP) injections improve key elements of the pathophysiologic mechanisms leading to erectile dysfunction (ED). AIM: To conduct the first double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of PRP injections in patients with mild and moderate ED. METHODS: Sixty sexually active patients with mild and moderate ED were randomly assigned to two sessions, with a one-month difference, of 10 mL PRP (n = 30) or placebo (n = 30) intracavernosal injections. An FDA-approved separation system was used. Patients were evaluated at 1, 3 and 6 months after completion of the treatment protocol. A per-protocol analysis was applied. All participants withheld any ED treatment during the trial. OUTCOMES: The achievement of minimal clinically important difference (MCID) in the International Index of Erectile Function - Erectile Domain (IIEF-EF) from baseline to 6 months after final treatment. Erectile function at all time points, as well as safety of PRP injections, were also evaluated. RESULTS: At 6 months, a MCID was achieved by 20/29 (69%) patients in the PRP group compared to 7/26 (27%) in the placebo group. The risk difference between the two groups was 42% (95%CI: 18-66), P < 0.001 and the baseline-adjusted mean between-group-difference in the IIEF-EF score was 3.9 points (95%CI: 1.8-5.9). Similarly, a statistically significant difference of both the number of participants attaining a MCID and the IIEF-EF score was also observed at the 1- and 3-month evaluation between the two groups. Accordingly, patients receiving PRP were more satisfied with the treatment. No adverse events were observed during the study period. CLINICAL IMPLICATIONS: Intracavernosal PRP injection therapy used as outlined in this trial appears to be a safe and effective short-term treatment for the management of mild to moderate ED. STRENGTHS & LIMITATIONS: We conducted the first clinical trial exploring the role of PRP in the management of ED. Conversely, our findings lack external validity due to single-center design. Furthermore, our results cannot be extrapolated to other PRP separation systems. CONCLUSIONS: PRP intracavernosal injections may be a promising addition to the urologist's armamentarium for the management of ED. Still, further high-quality studies are warranted to corroborate our findings. Evangelos P, Mykoniatis I, Pyrgidis N, et al. Platelet-Rich Plasma (PRP) Improves Erectile Function: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med 2021;18:926-935.

Prevalence of Erectile Dysfunction in Patients With End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Erectile dysfunction (ED) is an under-recognized clinical entity in men with end-stage renal disease (ESRD), and studies on renal transplant recipients, patients on dialysis, and patients starting dialysis report different prevalence rates and severity of ED among these groups. AIM: To determine the prevalence and severity of ED in patients with ESRD, assessed with the International Index of Erectile Function-15 and International Index of Erectile Function-5. METHODS: We performed a systematic review and meta-analysis of observational studies assessing the prevalence of ED in ESRD individuals. (PROSPERO ID: CRD42020182680). Records were identified by search in MEDLINE, Scopus, and CENTRAL databases and sources of gray literature until July 2020. We conducted a random-effects meta-analysis of proportions (double arcsine transformation). OUTCOMES: We included 94 studies with 110 patient group entries and a total of 10,320 ESRD male individuals with a mean age of 48.8 ± 14.25 years. RESULTS: Overall, 7,253 patients experienced ED. We estimated an overall pooled ED prevalence of 71% (95% CI: 67-74%, I2 = 92%). In the subgroup analyses, the pooled prevalence was 59% (95% CI: 53-64%, I2 = 92%) among renal transplant recipients, 79% (95% CI: 75-82%, I2 = 86%) in patients on hemodialysis, 71% (95% CI: 58-83%, I2 = 86%) in patients on peritoneal dialysis, and 82% (95% CI: 75-88%, I2 = 0%) in patients with ESRD starting dialysis. The prevalence of the severity of ED was also estimated. Further assessment of heterogeneity was conducted via sensitivity analysis, cumulative meta-analysis, and meta-regression of significant risk factors. CLINICAL TRANSLATION: Despite its high prevalence in patients with ESRD, ED constitutes an underestimated and taboo subject in this group. Therefore, arousing clinical concern among healthcare providers involved in ESRD management is more than necessary to screen and treat ED in patients receiving renal replacement therapy. STRENGTHS & LIMITATIONS: We estimated ED solely for ESRD, included the largest number of patients compared with previous studies and estimated ED prevalence as per severity and renal replacement therapy subgroups. Contrary, because we restricted our eligibility criteria to the International Index of Erectile Function, some studies assessing ED prevalence with other validated tools were not included in this meta-analysis. Moreover, the levels of heterogeneity among studies remained high after sensitivity and meta-regression analyses, and for some moderators, the results of the meta-regression might have been underpowered. CONCLUSIONS: ED is highly prevalent in patients with ESRD irrespective of the type of renal replacement therapy, thereby warranting clinical attention. Pyrgidis N, Mykoniatis I, Nigdelis MP, et al. Prevalence of Erectile Dysfunction in Patients With End-Stage Renal Disease: A Systematic Review and Meta-Analysis. J Sex Med 2021;18:113-120.

Sexual Dysfunction in Women With End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: In women with end-stage renal disease (ESRD), female sexual dysfunction (SD) remains underestimated. AIM: To explore the prevalence, correlates, diagnostic approach and treatment modalities of sexual symptoms in females with ESRD. METHODS: We performed a systematic review and meta-analysis to estimate both the prevalence of SD and the pooled Female Sexual Function Index (FSFI) scores in ESRD females. Similarly, for studies reporting the FSFI score before and after renal transplantation (RT), we estimated the effect of RT on sexual function. Further assessment of heterogeneity was conducted via subgroup and sensitivity analyses, cumulative meta-analysis and univariate meta-regression of important correlates. Records were identified through searching PubMed, Cochrane Library and Scopus databases as well as sources of grey literature until November 2020 (PROSPERO ID: CRD42020215178). OUTCOMES: We included 47 studies with 61 patient group entries and 3490 ESRD female individuals (median age: 45.2 years, ΙQR: 40.4-50.6). RESULTS: The SD prevalence in all females with ESRD was 74% (95%CI: 67%-80%, I2 = 92%) and the FSFI total score 16.1 points (95%CI: 14.3-17.8, I2 = 98%). The female SD prevalence was 63% (95%CI: 43%-81%, I2 = 92%) in renal transplant recipients, 80% (95%CI: 72%-87%, I2 = 91%) in hemodialysis patients and 67% (95%CI: 46%-84%, I2 = 90%) in peritoneal dialysis patients. The total FSFI score improved by 7.5 points (95%CI: 3.9-11.1, I2 = 92%) after RT. Older age and menopause were associated with higher SD prevalence. CLINICAL TRANSLATION: Female SD is highly prevalent in all ESRD women, but renal transplant recipients reported improved sexual function. STRENGTHS & LIMITATIONS: We provide the first study about SD in females and assessed the role of RT on sexual function. Contrary, none of the included studies evaluated the concomitant presence of distress with SD. The levels of heterogeneity were substantially high for all outcomes and we could not adjust for further correlates, which might have affected our measures. CONCLUSIONS: Sexual symptoms negatively affect the quality of life and warrants appropriate clinical attention, as they are an underdetermined and undertreated clinical entity in females with ESRD. Studies on treatment modalities of female SD in patients with ESRD are mandatory, as currently no relevant studies or clinical recommendations exist. Pyrgidis N, Mykoniatis I, Tishukov M, et al. Sexual Dysfunction in Women With End-Stage Renal Disease: A Systematic Review and Meta-Analysis. Sex Med Rev 2021;18:936-945.

Low-Intensity Shockwave Therapy (LiST) for Erectile Dysfunction: Is It Safe for Patients on Anticoagulant Medication?

INTRODUCTION: A significant percentage of men with vasculogenic erectile dysfunction (ED) use antiplatelet therapy because they have a history of cardiovascular disease. However, the safety of this novel treatment modality in patients under antiplatelet treatment has been based on anecdotal cases, and published data are lacking. The aim of this study is to examine the safety of low-intensity shockwave therapy (LiST) on a group of patients under antiplatelet therapy who were treated with LiST. METHODS: A pulled data analysis, conducted from November-December 2018, including 2 randomized clinical trials conducted at an Andrology outpatient clinic is presented. The 2 trials used the same design, the same shockwaves generator, as well as the same method of delivering the energy. The LiST protocol differed between the patients regarding LiST sessions number (6, 12, or 18), sessions frequency (1, 2, or 3 sessions/wk) and energy flux density used, which was either 0.05 or 0.1 mJ/mm2. The number of 5,000 pulses/session remained unchanged. For the purpose of the current study, patients receiving anticoagulant medication at the time of treatment and follow-up period were included in this analysis. All patients had a diagnosis of vasculogenic ED. According to the study protocol, after every treatment visit, as well as at 1 and 3 months after treatment, all patients reported any side effects or complications of the treatment; physical examination of the penis was performed before and after each treatment session, as well as at follow-up visits at 1 and 3 months. Penile ultrasonography was performed at baseline, as well as at 3 months' follow-up, at the same time with triplex ultrasonography by the same investigator. RESULTS: 138 patients were included in the 2 trials, whereas 135 (98%) of them finished the 3 months follow-up. 35 (25.3%) of them were under anticoagulant/antiplatelet medication during LiST. No bleeding events or any other side effects were reported. STRENGTHS & LIMITATIONS: The main strength of this article is that it is the first report on the safety of LiST on the specific group of cardiovascular patients with ED under anticoagulant/antiplatelet therapy. However, it is a pulled data analysis, based on 2 randomized studies, which did not have safety of LiST as a primary outcome. CONCLUSION: LiST seems to be a safe and well-tolerated treatment option for vasculogenic ED in patients on antiplatelet medication. Kalyvianakis D, Memmos D, Mykoniatis I, et al. Low-Intensity Shockwave Therapy (LiST) for Erectile Dysfunction: Is It Safe for Patients on Anticoagulant Medication? J Sex Med 2019;16:1478-1480.

The Basic Science Behind Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction: A Systematic Scoping Review of Pre-Clinical Studies.

INTRODUCTION: Despite recent promising clinical results, the underlying mechanism of action of low-intensity extracorporeal shockwave therapy (Li-ESWT) for erectile dysfunction (ED) is mostly unclear and currently under investigation. AIM: To systematically identify and evaluate evidence regarding the basic science behind Li-ESWT for ED, discuss and propose a putative mechanism of action, address the limitations, and imply insights for further investigation in the field. METHODS: Using Cochrane's methodologic recommendations on scoping studies and systematic reviews, we conducted a systematic scoping review of the literature on experimental research regarding Li-ESWT for ED and other pathologic conditions. The initial systematic search was carried between January and November 2017, with 2 additional searches in April and August 2018. All studies that applied shockwave treatment at an energy flux density >0.25 mJ/mm2 were excluded from the final analysis. MAIN OUTCOME MEASURE: We primarily aimed to clarify the biological responses in erectile tissue after Li-ESWT that could lead to improvement in erectile function. RESULTS: 59 publications were selected for inclusion in this study. 15 experimental research articles were identified on Li-ESWT for ED and 44 on Li-ESWT for other pathologic conditions. Li-ESWT for ED seems to improve erectile function possibly through stimulation of mechanosensors, inducing the activation of neoangiogenesis processes, recruitment and activation of progenitor cells, improving microcirculation, nerve regeneration, remodeling of erectile tissue, and reducing inflammatory and cellular stress responses. CLINICAL IMPLICATIONS: Improving our understanding of the mechanism of action of Li-ESWT for ED can help us improve our study designs, as well as suggest new avenues of investigation. STRENGTHS & LIMITATIONS: A common limitation in all these studies is the heterogeneity of the shockwave treatment application and protocol. CONCLUSION: Li-ESWT for ED, based on current experimental studies, seems to improve erectile function by inducing angiogenesis and reversing pathologic processes in erectile tissue. These studies provide preliminary insights, but no definitive answers, and many questions remain unanswered regarding the mechanism of action, as well as the ideal treatment protocol. Sokolakis I, Dimitriadis F, Teo P, et al. The Basic Science Behind Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction: A Systematic Scoping Review of Pre-Clinical Studies. J Sex Med 2019;16:168-194.

Low-Intensity Shockwave Therapy for Erectile Dysfunction: A Randomized Clinical Trial Comparing 2 Treatment Protocols and the Impact of Repeating Treatment.

BACKGROUND: There is lack of evidence-based optimization of the protocol for low-intensity shockwave therapy for erectile dysfunction. Furthermore, the safety and efficacy of repeating shockwave therapy have not been explored. AIM: To compare the efficacy and safety of 6 and 12 treatment sessions within a 6-week treatment period and investigate the effect of repeat treatment after a 6-month period in a 2-phase study. METHODS: Patients with vasculogenic erectile dysfunction that responded to phosphodiesterase type 5 inhibitors were randomized into 2 groups: low-intensity shockwave therapy sessions once (group A, n = 21) or twice (group B, n = 21) per week for 6 consecutive weeks (phase 1). Patients who completed 6-month follow-up were offered 6 additional sessions (phase 2); group A received 2 sessions per week and group B received 1 session per week. Patients were followed for 6 months. OUTCOMES: International Index for Erectile Function erectile function domain (IIEF-EF) score, minimally clinical important differences (MCIDs), Sexual Encounter Profile question 3 (SEP3) score, and triplex ultrasonographic parameters. RESULTS: In phase 1, groups A and B showed improvement in IIEF-EF score, MCID, SEP3 score, and mean peak systolic velocity compared with baseline. MCIDs were achieved in 62% of group A and 71% of group B, and the percentage of yes responses to SEP3 was 47% in group A and 65% in group B (P = .02). Mean peak systolic velocity at baseline and at 3-month follow-up were 29.5 and 33.4 cm/s for group A and 29.6 and 35.4 cm/s for group B (P = .06). In phase 2, group A showed a greater increase in the percentage of yes responses to SEP3 (group A = +14.9; group B = +0.3). When the impact of the total number of sessions received was examined, MCIDs in IIEF-EF score from baseline were achieved in 62%, 74%, and 83% of patients after 6, 12, and 18 sessions, respectively. No treatment-related side effects were reported. CLINICAL IMPLICATIONS: The total number of low-intensity shockwave therapy sessions affects the efficacy of erectile dysfunction treatment. Retreating patients after 6 months could further improve erectile function without side effects. 12 sessions can be delivered within 6 weeks without a 3-week break period. STRENGTHS AND LIMITATIONS: This study lacked a sham-controlled arm. However, all patients were randomized to different groups, and baseline characteristics were similar between groups. Also, all patients were confirmed by triplex ultrasonography to have arterial insufficiency. CONCLUSION: Patients can benefit more in sexual performance from 12 sessions twice per week compared with 6 sessions once a week. Shockwave therapy can be repeated up to a total of 18 sessions. Kalyvianakis D, Memmos E, Mykoniatis I, et al. Low-Intensity Shockwave Therapy for Erectile Dysfunction: A Randomized Clinical Trial Comparing 2 Treatment Protocols and the Impact of Repeating Treatment. J Sex Med 2018;15:334-345.

Low-Intensity Shockwave Therapy Improves Hemodynamic Parameters in Patients With Vasculogenic Erectile Dysfunction: A Triplex Ultrasonography-Based Sham-Controlled Trial.

BACKGROUND: Although several reports have documented the subjective improvement of erectile function after low-intensity extracorporeal shockwave therapy (LI-ESWT) in patients with vasculogenic erectile dysfunction (ED), objective assessment data of penile hemodynamics are lacking. AIM: To assess penile hemodynamics before and 3 months after LI-ESWT in a group of patients with documented vasculogenic ED. METHODS: This was a double-blinded, randomized, sham-controlled trial. Forty-six patients with ED were randomized; 30 underwent LI-ESWT and 16 had a sham procedure in double-blinded fashion. All patients underwent penile triplex ultrasonography by the same investigator immediately before and 3 months after treatment. Patient demographics, International Index of Erectile Function erectile function domain (IIEF-ED) score, and minimal clinically important difference were assessed at baseline and 1, 3, 6, 9, and 12 months after treatment. OUTCOMES: Changes in peak systolic velocity and resistance index as measured by triplex ultrasonography at baseline and 3 months after treatment were the main outcomes of the study. Secondary outcomes were changes in the IIEF-EF score from baseline to 1, 3, 6, 9, and 12 months after treatment and the percentage of patients reaching a minimal clinically important difference during the same period for the two groups. RESULTS: IIEF-EF minimal clinically important differences for the active vs sham group were observed for 56.7% vs 12.5% (P = .005) at 1 month, 56.7% vs 12.5% (P = .003) at 3 months, 63.3% vs 18.8% (P = .006) at 6 months, 66.7% vs 31.3% (P = .022) at 9 months, and 75% vs 25% (P = .008) at 12 months. Mean peak systolic velocity increased by 4.5 and 0.6 cm/s in the LI-ESWT and sham groups, respectively (P < .001). CLINICAL IMPLICATIONS: Such results offer objective and subjective documentation of the value of this novel treatment modality for men with vasculogenic ED. STRENGTHS AND LIMITATIONS: Strengths include the prospective, randomized, sham-controlled type of study and the assessment of penile hemodynamics. Limitations include the small sample and strict inclusion criteria that do not reflect everyday clinical practice. CONCLUSION: The present study confirms the beneficial effect of LI-ESWT on penile hemodynamics and the beneficial effect of this treatment up to 12 months. Kalyvianakis D, Hatzichristou D. Low-Intensity Shockwave Therapy Improves Hemodynamic Parameters in Patients With Vasculogenic Erectile Dysfunction: A Triplex Ultrasonography-Based Sham-Controlled Trial. J Sex Med 2017;14:891-897.

Sexual Response Models: Toward a More Flexible Pattern of Women's Sexuality.

INTRODUCTION: Recent research suggests that none of the current theoretical models can sufficiently describe women's sexual response, because several factors and situations can influence this. AIM: To explore individual variations of a sexual model that describes women's sexual responses and to assess the association of endorsement of that model with sexual dysfunctions and reasons to engage in sexual activity. METHODS: A sample of 157 randomly selected hospital employees completed self-administered questionnaires. MAIN OUTCOME MEASURES: Two models were developed: one merged the Master and Johnson model with the Kaplan model (linear) and the other was the Basson model (circular). Sexual function was evaluated by the Female Sexual Function Index and the Brief Sexual Symptom Checklist for Women. The Reasons for Having Sex Questionnaire was administered to investigate the reasons for which women have sex. RESULTS: Women reported that their current sexual experiences were at times consistent with the linear and circular models (66.9%), only the linear model (27%), only the circular model (5.4%), and neither model (0.7%). When the groups were reconfigured to the group that endorsed more than 5 of 10 sexual experiences, 64.3% of women endorsed the linear model, 20.4% chose the linear and circular models, 14.6% chose the circular model, and 0.7% selected neither. The Female Sexual Function Index, demographic factors, having sex for insecurity reasons, and sexual satisfaction correlated with the endorsement of a sexual response model. When these factors were entered in a stepwise logistic regression analysis, only the Female Sexual Function Index and having sex for insecurity reasons maintained a significant association with the sexual response model. CONCLUSION: The present study emphasizes the heterogeneity of female sexuality, with most of the sample reporting alternating between the linear and circular models. Sexual dysfunctions and having sex for insecurity reasons were associated with the Basson model.

Percutaneous Nephrolithotomy in a Patient with Mainz Pouch II Urinary Diversion: A Case Report.

Mainz pouch II is a reliable and viable technique of continent urinary diversion. Patients are at increased risk of long-term complications including urolithiasis of the upper urinary tract and reservoir. We report the case of a 67-year-old male with prior Mainz pouch II due to invasive bladder cancer treated for a large renal calculus. Percutaneous nephrolithotomy (PCNL) was successfully performed. Stone management in these type of patients is of increased interest due to existed "anatomical challenges" concerning the access and safety during the procedure. To our knowledge this is the first case of PCNL in a patient with Mainz pouch II that has been reported in the literature.

Tadalafil 5 mg once daily for the treatment of erectile dysfunction during a 6-month observational study (EDATE): impact of patient characteristics and comorbidities.

BACKGROUND: To explore the impact of patient-characteristics and relevant comorbidities on treatment continuation rates, effectiveness, and satisfaction in patients with erectile dysfunction (ED) who started or switched to tadalafil 5 mg once daily (TAD-OaD) at baseline. METHODS: In the EDATE observational study, phosphodiesterase-type-5 (PDE5)-inhibitor pretreated or naïve ED patients who started or switched to TAD-OaD were prospectively followed for 6 months. Time to discontinuation of TAD-OaD was estimated using the Kaplan-Meier product-limit method at Months 2, 4, and 6 in subgroups stratified by age (18 - 65 years and >65 years), PDE5-inhibitor pretreatment, ED-severity (mild, moderate, severe), and presence or absence of relevant comorbidities (BPH, diabetes, CVD, hypertension, dyslipidemia). LSmean change from baseline in International Index of Erectile Function (IIEF) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores and associated 95 % CIs were assessed using a mixed-model for repeated measures. Visit, ED etiology, and subgroups were included as fixed-effects. RESULTS: Overall, 778 patients received prescriptions for initiating or switching to TAD-OaD at baseline. At Month 2, >90 % of patients remained on TAD-OaD, except those aged >65 years (86.7 %) and patients with severe ED (89.0 %). More than 80 % of patients in all subgroups, except those aged >65 years (75.0 %), continued TAD-OaD at Month 6. There was a significant LSmean negative effect on IIEF- EF domain-score improvement for BPH (LSmean effect [95 % CI]: -2.77 [-4.98, -0.55], p = 0.014), previous PDE5-inhibitor treatment (-2.13 [-3.33,-0.94], p < 0.001), and mild vs moderate ED (-2.00 [-3.54,-0.46], p = 0.011); the latter possibly linked with a bigger treatment-effect in those with more severe ED at baseline. The LSmean effect on change in IIEF-EF was significantly positive for diabetes (2.28 [0.64,3.92], p = 0.007), most likely because those with diabetes had more severe ED at baseline. For all other parameters, no statistically significant LSmean effects in IIEF-EF changes were observed. No comorbidity or baseline-characteristic except age (18 - 65 years vs >65 years: 11.25 [2.96,19.54], p = 0.008) affected changes in EDITS. CONCLUSIONS: Under routine clinical conditions, treatment continuation rate or satisfaction does not seem to be significantly affected by the presence of comorbidities in men who choose ED-treatment with TAD-OaD. The magnitude of treatment effectiveness was affected by certain baseline characteristics and comorbid conditions. TRIAL REGISTRATION: The study (H6D-EW-LVIU) is registered in the German VfA Registry of Non-Interventional Studies (Verband Forschender Arzneimittelhersteller) since 06 December 2011; available at: http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb/nis-details/_741 .