Salter CA. et al., 2025: A critical analysis of the methodological limitations in trials of low-intensity shockwave therapy for erectile dysfunction.

Carolyn A Salter, Hisanori Taniguchi, Daniel J Kim, John P Mulhall
Sex Med Rev. 2025 Nov 30:qeaf065. doi: 10.1093/sxmrev/qeaf065

Abstract

Introduction: Low-intensity shockwave therapy (LiSWT) is a novel treatment option for patients with erectile dysfunction (ED). To date, numerous randomized controlled trials (RCTs) and cohort studies have been published.

Objectives: To critically evaluate the methodology and limitations of the published studies on LiSWT for ED.

Methods: A literature search was performed. We excluded studies that compared and/or combined LiSWT to other therapies. In the context of multiple studies from the same center with identical populations and study design, we selected the studies with the largest patient population and/or longest follow-up. Attention was focused on patient demographics, device parameters, treatment protocols, endpoints, and follow-up schedules.

Results: 45 studies (25 cohort, 20 RCTs) using 9 different LiSWT devices were analyzed. Most studies excluded men with severe ED: 6 included men with pelvic surgery and/or radiation and 22 studies included phosphodiesterase 5 inhibitor non-responders. The population size for the cohort studies had mean 61.12 patients (SD 80.34), median 40.0 (IQR 27-54). In the RCTs, the mean per arm was 38.13 patients (SD 19.25), median 35 (IQR 23-42.5). Patients received between 3000 and 90 000 total shocks during the treatment courses, with 1-5 sessions per week and 2-10 application sites included. The most common endpoint was change in the International Index of Erectile Function. Only 17 trials evaluated objective endpoints, such as penile duplex Doppler ultrasound. Study follow-up duration ranged between 1 and 36 months with a median of 6 months.

Conclusion: The methodology applied to the published LiSWT studies is remarkably heterogeneous, with a 30-fold difference in shock number and a 5-fold difference in weekly session number and number of application sites. These data emphasize the current inability to compare results across studies using nine different devices and disparate treatment protocols.

Comment Jens Rassweiler

Introduction

Low-intensity shockwave therapy (Li-SWT) has been investigated for the treatment of erectile dysfunction (ED) over the past 15 years. While some animal studies and human trials suggest its effectiveness, the precise mechanism of action remains unclear. Initial studies, including a pilot by Vardi et al. in 2010, have led to various randomized controlled trials (RCTs) and meta-analyses indicating improvements in erectile function scores (IIEF-EFD) for patients receiving Li-SWT compared to sham treatments. However, many questions persist regarding optimal patient selection, treatment protocols, and the durability of treatment effects.

Methods

A literature review focused on RCTs and cohort studies involving Li-SWT for ED was conducted, filtering for human trials in English with detailed methodologies. Studies that involved other conditions, combined therapies, or lacked sufficient detail were excluded. A total of 45 studies (20 RCTs and 25 cohort studies) were included in the analysis, examining patient demographics, treatment parameters, and funding sources.

Results

- Devices and Shockwave Parameters: Nine different Li-SWT devices were identified, with the Duolith SD1 being the most commonly used. Treatment parameters varied widely across studies in terms of energy flux density, frequency, application sites, and total number of shocks delivered.

- Funding: Most studies were funded by industry, raising concerns about potential bias.

- Endpoints: The follow-up duration across studies varied significantly, with the IIEF score being the most common primary endpoint. Only a minority evaluated objective outcomes.

Discussion

Despite the potential of Li-SWT, it is still considered investigational by major medical organizations due to the lack of comprehensive clinical data. The studies reviewed exhibit considerable methodological limitations, including small sample sizes, lack of power analysis, and variability in treatment protocols. Many studies excluded men with severe ED or those who did not respond to PDE5 inhibitors, limiting the generalizability of the findings.

The article emphasizes the critical need for larger, well-designed RCTs to establish the efficacy of Li-SWT. Acknowledging the placebo response in ED trials, the researchers argue for better characterization of patient populations and the use of validated instruments to mitigate bias. Moreover, studies should aim for longer follow-up durations to assess the durability of treatment effects.

Conclusion

The review highlights significant methodological challenges in current Li-SWT research, indicating that while Li-SWT has the potential to transform ED treatment, much remains to be understood about its optimal application. Due to the different types of shock wave generation (i.e. electromagnetic, piezoelectric, electrohydraulic) the applied energy density might be difficult to compare. Probably, the methodology used with the Duolith SD1 could be taken as a standard.

Future studies must focus on standardizing methodologies, adequately powering trials, and thoroughly characterizing patient populations to clarify the efficacy and safety of this treatment modality.

Jens Rassweiler