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.

Platelet-rich plasma for the treatment of erectile dysfunction: a systematic review of preclinical and clinical studies.

INTRODUCTION: There has been tremendous growth in regenerative medicine during the last decade. For erectile dysfunction (ED), after the inclusion of low-intensity shockwave therapy as a treatment modality for ED management by the European Association of Urology sexual health guidelines, intracavernosal injection of platelet-rich plasma (PRP) has gained popularity between urologists and patients as a novel ED therapeutic modality with initial promising results. However, limited clinical data exist regarding efficacy and safety in patients with ED. Furthermore, despite numerous preclinical studies in other tissues and organs, the mechanism of action for restoring erectile function remains undetermined. OBJECTIVES: This systematic review aims to present the current status of preclinical and clinical evidence regarding the use of PRP as treatment option for ED. METHODS: A systematic literature search was conducted using PubMed, Cochrane, and ScienceDirect databases, until February 2023 for studies exploring the effect of PRP on ED. RESULTS: We identified 517 articles, 23 of which were included in this review. These were 7 preclinical (of which 1 was a comparative trial and 6 were placebo-controlled randomized controlled trials) and 16 clinical studies (of which 1 was a comparative trial, 5 were randomized trials, and 2 were placebo-controlled randomized controlled trials). Preclinical data support the regenerative role of PRP in erectile tissue, in accordance with existing evidence in other tissues. Randomized clinical studies, as well as the first 2 available randomized, placebo-controlled clinical trials, showed promising efficacy and a lack of any adverse events. CONCLUSION: As PRP for ED is widely used worldwide, there is an urgent need for high-quality studies with long-term follow-up. Standardization of research protocols, especially on the quality of PRP preparation, is also needed.

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.

The Effect of Phosphodiesterase-type 5 Inhibitors on Erectile Function: An Overview of Systematic Reviews.

Background: Multiple systematic reviews explore the effect of phosphodiesterase type 5 (PDE5) inhibitors on erectile dysfunction (ED), with each study addressing specific outcomes. However, physicians and policymakers require a holistic approach of this topic. Objective: To summarize the current evidence regarding the efficacy and safety of PDE5 inhibitors for the management of ED through an overview of systematic reviews. Methods: Studies were identified by searching PubMed, Web of Science, Cochrane Library and Scopus databases, as well as sources of grey literature until June 12, 2021 (PROSPERO: CRD42020216754). We considered systematic reviews, meta-analyses or network meta-analyses of randomized trials that provided outcomes about the efficacy and safety of any approved PDE5 inhibitor (avanafil, sildenafil, tadalafil and vardenafil). We constructed forest plots for meta-analytic effects regarding the change in erectile function, adverse events and dropouts after administration of PDE5 inhibitors in the general population and in specific patient groups. Results: We included 23 studies with 154,796 participants and a total of 258 meta-analytic effects. Sildenafil 25 mg [Weighted Mean Difference (WMD): 13.08, 95% Confidence Interval (CI): 10.1-16.06] seemed to be statistically superior to all interventions in improving erectile function compared to placebo, but studies with low-dose sildenafil are lacking. Moreover, comparing among different PDE5 inhibitors, sildenafil 50 mg or sildenafil 100 mg were considered the most effective compounds in the general population. The latter derived, however, predominantly from indirect comparisons among different PDE5 inhibitors. Still, sildenafil 100 mg was associated with more treatment-related adverse events and dropouts. Interestingly, low-dose daily tadalafil may be more effective than high-dose on-demand tadalafil (WMD: 1.24, 95% CI: 0.03-2.44). Furthermore, testosterone and PDE5 inhibitors in patients with ED and hypogonadism seem to further improve symptoms, while the addition of a-blockers in patients with urinary symptoms treated with PDE5 inhibitors does not provide additional benefits (WMD: -0.8, 95% CI: -1.65-0.06). Conclusion: Although the efficacy and safety of PDE5 inhibitors, compared to placebo, is well-documented, the existing evidence comparing different PDE5 inhibitors is low. Therefore, high-quality, head-to-head, trials comparing different PDE5 inhibitors are necessary to determine their ideal dosage and formulation based on their safety and efficacy profile. Systematic Review Registration: PROSPERO, identifier [CRD42020216754].

Effect of phosphodiesterase-type 5 inhibitors on erectile function: an overview of systematic reviews and meta-analyses.

INTRODUCTION: Phosphodiesterase-type 5 inhibitors (PDE5i) are the recommended first-line treatment for erectile dysfunction. Previous systematic reviews and meta-analyses suggest that they are a safe and effective option in many patient groups. Similarly, PDE5i may be effective as part of combination therapy in non-responders to PDE5i. We will generate an overview of systematic reviews, meta-analyses and network meta-analyses aiming to summarise the available knowledge regarding the efficacy and safety of PDE5i in the general population and in multiple subgroups of patients. METHODS AND ANALYSIS: This overview was designed in accordance with the PRIO-harms and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and its protocol was registered at PROSPERO. We will systematically search PubMed, Web of Science, Cochrane Library and Scopus databases from inception to November 2020 without any language restrictions. We will include systematic reviews or meta-analyses: (1) comparing the efficacy and safety of any dose of PDE5i with each other, with placebo or with other effective treatments for the management of erectile function; (2) exploring the use of any PDE5i alone or in combination with other treatment modalities in the general male population or in specific subgroups and (3) conducted with systematic procedures. Our overview will employ the AMSTAR 2 tool to evaluate the quality of the included studies and the Grading of Recommendations Assessment, Development and Evaluation approach to assess the strength of evidence for all outcomes. We will construct forest plots of risk estimates with the corresponding CI for all outcomes. ETHICS AND DISSEMINATION: In this overview, we will undertake an extensive literature search in an attempt to evaluate the potential benefits and risks of treatment with one PDE5i versus another or versus placebo and provide recommendations for clinicians and policy-makers. No ethical approval is required. PROSPERO REGISTRATION NUMBER: CRD42020216754.

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.

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.

Evaluation of a low-intensity shockwave therapy for chronic prostatitis type IIIb/chronic pelvic pain syndrome: a double-blind randomized sham-controlled clinical trial.

BACKGROUND: Currently, there is no efficacious treatment method for chronic prostatitis type IIIb/chronic pelvic pain syndrome (CP/CPPS). Aim of the study was to investigate and compare the efficacy and safety of low-intensity shockwave therapy (LiST) vs. sham treatment in CP/CPPS patients. METHODS: Patients with CP/CPPS diagnosis were randomized in this prospective, sham-controlled, double-blind study either to the active groups (Group B, C) who received 5000 shockwaves per session with energy flux density 0.1 mJ/mm2 or to the sham group (Group A) who received 5000 shockwaves from a visually identical sham probe. All groups underwent six sessions (once/week). LiST effects on pain, micturition, quality of life (QoL), and erectile function were evaluated at 4, 12, and 24 weeks after treatment. The parameters were investigated using validated questionnaires. Uroflowmetry and post void residual calculation were performed at baseline and at 4- and 12-week FU visit. Prostate mpMRI and PSA measurement were performed at baseline and 12-week FU visit. RESULTS: Overall, 45 men were randomized to the active (n = 30) and sham groups (n = 15). Regarding impact of LiST in National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) total, pain, and QoL subdomains scores a clear and persistent in all FU timepoints improvement was found compared to sham treatment. NIH-CPSI urinary subdomain, International Prostate Symptom Score [IPSS], PSA, and mpMRI-PIRADS scores did not differ between the two groups. The mean difference between the LiST and sham group in the change of the NIH-CPSI pain-domain score (Q1-4) from baseline to 12 weeks after final treatment which was 3.3 (95% CI, 1.8, 4.7). Perineal LiST was easy and safe to perform without anesthesia or any side-effects. CONCLUSIONS: LiST seems to be a safe and effective treatment option for CP/CPPS, considerably improving pain and quality of life. Lack of any side-effects, and the potential for repetition make LiST a promising treatment choice for CP/CPPS patients.

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.

Low-intensity shockwave therapy (LiST) for erectile dysfunction: a randomized clinical trial assessing the impact of energy flux density (EFD) and frequency of sessions.

The impact of energy flux density (EFD) used on low-intensity shockwave therapy (LiST) for erectile dysfunction (ED) has not been explored. Our aim was to compare EFD 0.05 versus 0.10 mJ/mm2 regarding efficacy and safety of 12-treatment sessions when applied two or three times per week. Ninety-seven patients with vasculogenic ED, PDE5 inhibitors users were randomized into four groups, to receive 12 LiST sessions. Group A (n = 24) : two sessions per week, EFD 0.05 mJ/mm2; Group B (n = 24): three sessions per week, EFD 0.05 mJ/mm2; Group C (n = 24): two sessions per week, EFD 0.10 mJ/mm2; Group D (n = 25): three sessions per week, EFD 0.10 mJ/mm2. International Index for Erectile Function-Erectile Function domain (IIEF-EF), Minimally clinical important differences (MCID), sexual encounter profile, and triplex ultrasonography parameters were used to asses erectile function. Eighty-nine patients completed the 6-month follow-up (FU). All four groups improved in mean IIEF-EF score, average SEP3 "Yes" response rates at 6-month FU visit compared with baseline (p < 0.001). MCID at 6-month FU visit was achieved in 82.6%, 77.3%, 87%, and 81% in Groups A, B, C, and D, respectively. Mean PSV (cm/s) at baseline versus 3-month FU visit were 30.32 versus 34.67 for Group A, 30.02 versus 35.02 for Group B, 30.2 versus 36.02, for Group C, 29.43 versus 34.3 for Group D (p < 0.01). There were no statistical significant differences in the change of all outcome measures assessing erectile function between different sessions frequency. A tendency for better efficacy using EFD 0.10 mJ/mm2 was noticed, although it did not reach statistical significance. No treatment-related side-effects were reported. This study lacks a sham-controlled arm. However, all patients were randomized to the four groups, and baseline characteristics were similar between the groups. Moreover, arterial insufficiency was confirmed among all patients by penile triplex ultrasonography. Conclusively, patients may benefit equally when sessions are applied either two or three per week. An EFD of 0.10 mJ/mm2 could result in better outcomes, but further studies are needed to validate this observation.

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.

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.