Efficacy of low-intensity extracorporeal shock wave therapy for erectile dysfunction: updated meta-analysis of randomized trials

Abstract

Background

Low-intensity extracorporeal shockwave therapy (Li-ESWT) is proposed for the treatment of erectile dysfunction (ED).

Materials and methods

Randomized controlled trials (RCTs) that compared Li-ESWT with sham therapy in patients with vasculogenic ED were included. The International Index of Erectile Function – Erectile Function (IIEF-EF) domain score, increase in the Erection Hardness Score (EHS), and improvement in Sexual Encounter Profile (SEP) 2 and SEP-3 were assessed.

Results

This meta-analysis of 12 RCTs, including 882 men with vasculogenic ED, demonstrated a statistically significant improvement in IIEF-EF score (an improvement from baseline as well as MCID) and EHS (patients with EHS ≥ 3) following LI-ESWT compared to sham therapy.

Conclusion

The results support the role of Li-ESWT as a potential treatment for ED.

PLAIN LANGUAGE SUMMARY

Low-intensity shockwave therapy (Li-ESWT) involves using gentle shockwaves to treat erectile dysfunction (ED) which is when a man has difficulty getting or maintaining a firm erection for sexual activity In a recent study looking at 12 research projects involving 882 men with ED caused by blood vessel problems, Li-ESWT showed significant improvements in their ability to have and maintain erections compared to fake treatments.

KEY FINDINGS

Improved Erectile Function: Men who got Li-ESWT saw a big improvement in their ability to get and keep erections.

Harder Erections: The treatment also made erections harder, which means better sexual performance.

Positive Outlook: These results suggest that Li-ESWT could be helpful in treating ED, giving hope to those dealing with this problem.

WHY IT MATTERS

Finding effective treatments like Li-ESWT is important in improving sexual health and overall well-being for men with ED. This matters because existing treatments like medications and devices often fall short, leaving many with unresolved ED issues.

CONCLUSIONS

Li-ESWT seems promising as an initial treatment for ED, but more high-quality studies with longer follow-ups are needed to confirm its effectiveness as a standard treatment.

ARTICLE HIGHLIGHTS

• Subgroup analysis based on specific target populations (vasculogenic ED, PDE5i responders, and non-responders) shows a statistically significant improvement in the IIEF-EF score.

• Pooled analysis demonstrates a significant improvement in Erection Hardness Score (EHS) in the Li-ESWT treatment group compared to the control group.

• Improvement in Sexual Encounter Profile 2 (SEP-2) did not significantly differ between the treatment and control groups, while SEP-3 showed a significant improvement in the Li-ESWT treatment group.

• These findings suggest that Li-ESWT could be a potential noninvasive first-line treatment for ED, but further high-quality randomized controlled trials with long-term follow-up are needed to establish its efficacy as a standard treatment.

1. Introduction

Erectile dysfunction (ED) is characterized by the inability to attain and sustain a satisfactory penile erection for the purpose of engaging in sexual intercourse [1]. According to the Massachusetts male aging study, the combined prevalence of minimal, moderate, and complete erectile dysfunction was 52% [2]. The prevalence of erectile dysfunction tripled from 5 to 15% between subjects ages 40 and 70 years. Another study estimated the increase of erectile dysfunction worldwide from 152 million in 1995 to 332 million in 2025, with the largest increase predicted in developing parts of the world i.e., Africa, Asia, and South America [3]. A study conducted in 2016 across 8 countries; Italy, Brazil, Germany, China, France, Spain, the UK, USA, found the overall ED prevalence to be 40.5% ranging from 37.2% in Brazil to 48.6% in Italy [4]. The reported prevalence figures for erectile dysfunction are likely to be significantly underestimated due to several factors. One contributing factor is reporting bias, where individuals may be hesitant to openly discuss their ED symptoms or may not seek medical attention for this condition. Cultural factors can also play a role, as certain societies may stigmatize discussions about sexual health, leading to underreporting of erectile dysfunction cases. Furthermore, many healthcare providers may not routinely inquire about their male patients’ sexual health, missing opportunities to identify and address erectile dysfunction. Additionally, the sensitive nature of erectile dysfunction can stir feelings of embarrassment and shame, further discouraging individuals from disclosing their symptoms. Therefore, it is important to recognize that the reported prevalence rates of erectile dysfunction may not accurately reflect the true extent of this condition in the population [5].

The inability to attain and sustain a satisfactory penile erection can be attributed to various underlying factors that affect the penile arteries, nerves, hormone levels, smooth muscle tissue, corporal endothelium, or tunica albuginea. There is a recognized correlation between erectile dysfunction and conditions such as cardiovascular disease, diabetes mellitus, hyperlipidemia, and hypertension, among others. Endothelial dysfunction emerges as a shared pathway in many of these patients, playing a significant role in the development of ED [6]. The causes of erectile dysfunction can be physiologic, neurogenic (diabetes, multiple sclerosis), psychologic (performance anxiety, depression), and/or pharmacologic (diuretics, antihypertensives, antidepressants). Even though erectile dysfunction can generally be treated with presently accessible medications and devices, around 20% of patients don’t respond well to them. In patients with diabetes mellitus or those who have undergone radical prostatectomy, the failure rate is up to 40% [7].

The complications associated with erectile dysfunction primarily involve emotional aspects, affecting both the patient and their partner. Erectile dysfunction can lead to strained relationships and have a significant negative impact on the overall quality of life for those affected. Additionally, it is extremely important to consider the potential coexisting cardiovascular pathologies and diabetic complications that often accompany ED, as they can introduce further health-related challenges and implications [8].

The combination of heightened public awareness and the widespread availability of effective oral medications has led to a greater number of men actively seeking treatment for erectile dysfunction. Consequently, there has been a notable rise in primary care consultations and referrals to specialized secondary care. The first line treatment for erectile dysfunction according to American Urology Association guidelines is phosphodiesterase 5 inhibitors (sildenafil, tadalafil, avanafil, vardenafil) which work by inhibiting the enzyme which degrades CGMP thus leading to increased nitrogen dioxide and smooth muscle relaxation [9]. They, however, require appropriate neural stimulation to the penis, have lower effectiveness rates in diabetics, and are contraindicated in patients taking nitrates [10]. The use of oral phosphodiesterase type 5 inhibitors (PDE5is) or intra-cavernosal injections of vasodilating agents are highly effective and generally safe, with rare occurrences of unwanted or adverse effects. However, they share a significant limitation: they do not address the underlying physiological factors responsible for erectile dysfunction. These treatments are typically taken as needed, prior to sexual activity, and their effects are temporary. Although daily use of a PDE5i partially addresses some of these issues, it still does not modify the underlying mechanisms of erectile function. Furthermore, there is limited evidence supporting its long-term effects on erectile tissue [11].

Other standard treatments for erectile dysfunction include penile implants, vacuum erection devices, intra-cavernosal injections, and intraurethral (IU) alprostadil suppositories, however, varying levels of invasiveness and the commitment demands associated with these therapies discourage their use and increase the rate of discontinuation in patients. Novel treatments for ED include platelet-rich plasma therapy, stem cell therapy, and extracorporeal shockwave therapy [12].

Low-intensity extracorporeal shockwave therapy (Li-ESWT) is a novel therapy proposed for the treatment of erectile dysfunction. Li-ESWT involves the application of focused yet weak shockwaves to a specific organ. These shockwaves interact with the deep tissues, causing mechanical stress and microtrauma. Shock waves cause microtrauma in the form of direct mechanical damage and the production of thermal energy through angiogenesis. The increased blood flow, in turn, results in improved erectile function [13,14]. Low-intensity extracorporeal shockwave therapy has previously demonstrated success in treating kidney stones and painful musculoskeletal conditions such as plantar fasciitis and lateral epicondylitis [15,16]. Recently several studies have emerged for the assessment of Li-ESWT for the treatment of ED; however, most of them are small-sized and show conflicting results [17].

This updated meta-analysis aims to determine the efficacy of low-intensity extracorporeal shockwave therapy for the treatment of erectile dysfunction. By looking at the evidence from randomized controlled trials (RCTs), we will evaluate the effects of Li-EWST on the Erection Hardness Score (EHS) and International Index of Erectile Function-erectile function domain (IIEF-EF) in patients suffering from erectile dysfunction.

2. Materials and methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed while conducting this study [18]. The assessment of multiple systematic reviews (AMSTAR) 2 tool was used to evaluate the quality of included articles [19].

2.1. Data sources and search strategy

To identify relevant studies on low-intensity extracorporeal shockwave therapy for erectile dysfunction, a systematic search was conducted. The search encompassed electronic databases, including PubMed and Cochrane Central, from their inception until January 2022 and no restrictions were applied regarding language or time. The search strategy involved using keywords and their corresponding MeSH terms, such as “low-intensity shockwave therapy” and “erectile dysfunction.” Boolean operators “AND” and “OR” were used, along with abbreviations and MeSH terms, to refine the search. Grey and white literature sources were also curried, and the bibliographies of relevant review articles were examined to ensure comprehensive coverage of the topic.

2.2. Inclusion and exclusion criteria

Articles were selected if they met the predefined eligibility criteria for inclusion: (i) low-intensity extracorporeal shockwave therapy with sham therapy (ii) were randomized controlled trials (iii) included vasculogenic ED patients (iv) reported at least one of the following outcomes: change in IIEF-EF score, increase in EHS score, improvement in Sexual Encounter Profile question 2 (SEP-2) and Sexual Encounter Profile question 3 (SEP-3).

The exclusion criteria included studies on the patient populations with erectile dysfunction associated with Peyronie’s disease, chronic pelvic pain syndrome, diabetes mellitus, or radical prostatectomy. Single-arm studies, letters to the editor, editorials comments, studies on animal models, narrative reviews, and case reports were also excluded. Phosphodiesterase usage, causes, and severity of erectile dysfunction were not treated as factors contributing to study exclusion. Any disagreements between the two independent reviewers (SIA, RA) regarding study selection were resolved by discussion and mutual consensus with a senior investigator (AE).

2.3. Data extraction and quality assessment of studies

The articles retrieved from the systematic search were exported to EndNote Reference Library Software, where duplicates were screened and removed. The remaining articles were screened independently by two authors (SIA, RA) using the abstract and introduction sections. The same authors performed full-text reviews and data extraction and then cross-checked for any errors by a senior reviewer (AE). Any differences or disagreements were settled by discussion.

The extracted data covered primary outcomes including mean IIEF score, i.e., International Index of Erectile Function, change in mean IIEF score from baseline, EHS, i.e., Erection Hardness Score, and improvements in SEP2 and SEP3 values, all being measures through which erection changes may be quantified. Study characteristics and patients’ baseline characteristics were extracted and systematically tabulated in Table 1 of the text to aid our data extraction.

Table 1.

Characteristics of the included studies.

		1	2	3	4	5	6	7	8	9	10	11	12
Study		Sramkova et al.	Kim et al.	Eric chung et al.	Viney et al.	Yamacake et al.	Fojecki et al.	Olsen et al.	Yee et al.	Kitrey et al.	Kalyvianakis et al.	Sirini et al.	Vardi et al.
Publication Year		2019	2020	2022	2020	2018	2017	2015	2014	2016	2017	2015	2012
Follow up		12 wks	7 wks	26 wks	26 wks	52 wks	4 wks	5 wks	4 wks	4 wks	52 wks	52 wks	4.3 wks
Weeks of treatment		2	6	6	4	3	9	5	9	9	9	9	9
No. of shocks per treatment		6000	3000	3000	5000	2000	600	3000	1500	1500	1500	1500	1500
Total shocks		24000	36000	36000	20000	12000	3000	15000	18000	18000	18000	18000	18000
Patient population	Treatment	30	38	30	40	10	58	51	30	37	30	60	40
	Control	30	43	30	36	10	63	54	28	18	16	17	20
IIEF-EF score before treatment	Treatment	12.8 ± 3.9	16.6 ± 3.0	14.6 ± 3.8	12.3 ± 2.6	10.9 ± 5.1	10.9	–	10.2 ± 3.8	7(IQR)	13.8 ± 3.6	9.5	12.6 ± 0.75
	Control	13.1 ± 3.6	16.7 ± 3.2	14.8 ± 3.6	12.75 ± 2.6	14.9 ± 3.0	11.5	–	10.2 ± 3.8	8(IQR)	14.6 ± 3.4	9.2	11.5 ± 0.86
Change in IIEF-EF score	Treatment	7.7 ± 1.1	2.6	6.8	1.75 ± 2.0	4.8	2.2	–	5.3 ± 5.5	5	18.46 ± 3.6 (1m)	12.5	6.7
	Control	2.5 ± 0.8		–	<0.0001 ± 3.5	–	2.5	–	3.8 ± 3.6	0	16.43 ± 3.5 (1m)	1.4	3
EHS	Treatment	3.6 ± 0.25	3.1 ± 0.6	2.6 ± 0.4	–	2.6 ± 0.84	–	29	–	20	–	47	31
	Control	2.4 ± 0.3	2.4 ± 0.9	1.3 ± 0.7	–	2.4 ± 0.7	–	5	–	0	–	0	7
Type of machine		PiezoWave2 and FBL10	MT2000H Urontech	2nd gen Duolith SD1	Renova Direx	Swiss dolorclast by EMS	FBL10	Storz	Omnispec ED1000	Omnispec ED1000	Omnispec ED1000	Omnispec ED1000	Omnispec ED1000

2.4. Statistical analysis

Review Manager 5.3 software (Cochrane Collaboration, London UK) was used to assess the extracted data. According to data types and evaluation purposes, the most appropriate effect size and statistical analysis methods were chosen. Risk ratios (RRs) with 95% CI were applied for dichotomous variables, a random-effects model was used, and then forest plots for appropriate outcomes were created. The heterogeneity between different studies was calculated via Higgin’s I² value with ranges from 0 to 50% is considered acceptable, from 50 to 75% moderate, and more than 75% significantly heterogeneous. Finally, via Begg’s test, a funnel plot was graphed to check for any publication inconsistency. P-value <0.05 was considered statistically significant for all of the aforementioned analyses. Subgroups were made according to different patient populations, including vasculogenic ED patients based on their response to oral phosphodiesterase type 5 inhibitors. Sensitivity analyses were performed by removing different studies, but they produced only minimal changes in the overall heterogeneity estimate.

3. Results

3.1. Study selection

After a comprehensive review of the literature of 896 articles for eligibility, we selected 12 RCTs that met the inclusion criteria, including 862 patients [15,20–30]. The rationale behind selecting only RCTs was their quality to limit the bias inherent to other study designs and therefore provide the highest level of evidence for studying the relationship between intervention and outcomes. Figure 1 shows the literature exclusion and inclusion stages flowchart, the reasons, the number of excluded studies, and finally, the number of articles.

Figure 1.

Effect of Li-ESWT on mean IIEF-EF score.

3.2. Characteristics of selected studies

The analysis included a total of 862 patients, with 504 patients receiving low-intensity extracorporeal shockwave therapy while 378 patients were in the control group receiving sham therapy. Table 1 summarizes the basic characteristics of the 12 selected studies included in the analysis. All twelve RCTs included patients with vasculogenic erectile dysfunction. Among the selected studies, four studies (Vardi et al., Kitrey et al., Srini et al., and Chung et al.) exposed their patients to 12 sessions of Li-ESWT therapy to assess erectile function, two studies (Sremkova et al. and Vinay et al.) exposed their treatment groups to 4 sessions, and two studies (Kim et al. and Yee et al.) exposed Li-ESWT groups to 6 sessions. In the studies, Fojecki et al. and Olsen et al., patients were exposed to Li-ESWT for 5 sessions. Kalyvianakis et al. included patients who were at least 18 years old, had erectile dysfunction for at least 6 months, and were at least partial responders to PDE5 inhibitors. Thereafter, following 4 weeks washout period treatment group was exposed to a total of 12 sessions of low-intensity shockwave therapy to assess for IIEF. In the study by Vinay et al., a treatment group of 40 men received 5000 shocks/session and assessed its treatment and sham group for IIEF-EF, EHS, SEP2, SEP3, and GAQ1. The mean IIEF-EF scores were assessed at different post-treatment follow-up intervals of 1,3,6, and 9 months, allowing for a comprehensive evaluation of the treatment’s effectiveness over time.

3.3. Risk of bias

To evaluate the risk of bias within the study, we used Cochrane Collaboration’s risk of bias tool wherein the risk was categorized into either high, low, or unclear, and its assessment was done under several domains; selection bias (random sequence generation, allocation concealment), performance bias, i.e., blinding of patients and staff, detection bias, i.e., blinding of outcome assessment, attrition bias, i.e., incomplete outcome data, reporting bias, i.e., selective reporting, and other bias.

3.4. Results of the meta-analysis

3.4.1. Mean IIEF-EF score

Overall pooled analysis reveals that the mean IIEF-EF score increased significantly in the treatment group compared with the control group (MD: 2.28; 95% CI [1.32, 3.24]; p < 0.0001).

In comparison to baseline scores, the mean IIEF-EF score post-treatment ranged from 11.0 to 22.0 in the treatment group versus 8.14 to 18.80 in the sham group. There was significant heterogeneity among the nine trials, I² = 85%. Sensitivity analyses performed by excluding Sirini et al. caused heterogeneity to decrease to 63% and the results remained statistically significant. Change in mean IIEF-EF scores were similar at follow-ups of 1, 3, 6, 9, and 12 months (P-interaction = 0.98) (Figure 1).

3.4.2. Change in IIEF-EF score

Our pooled analysis demonstrated that the IIEF-EF score increased significantly in the treatment group as compared to the control group (Figure 2). Pooled studies were stratified according to specific target populations in to vasculogenic ED, PDE5i responders, and non-responders. The overall mean difference between treatment and sham groups in the change from baseline to 1-month post-treatment follow-up was statistically significant (MD: 3.78; 95% CI [1.65, 5.91], I² = 92%, p < 0.00001). Our subgroup analysis demonstrated that the change in IIEF-EF Score was similar between the PDE5i responders and nonresponder group (P-interaction = 0.56).

Figure 2.

Effect of Li-ESWT on change in IIEF-EF score.

3.4.3. Increase in EHS score

Eight studies provided data for the increase in EHS scores from baseline (Figure 3). Pooled analysis shows that EHS scores were significantly improved in the treatment group in contrast to the control group (MD: 5.44; 95% CI [2.40, 12.33]; I² = 65%, p-value = 0.001). Our subgroup analysis demonstrated that changes in EHS scores were similar between PDE5i responders, PDE5i non-responders, and kidney-transplant patients (P-interaction = 0.30).

Figure 3.

Effect of Li-ESWT on increase in EHS.

3.4.4. Improvement in SEP-2 and SEP-3

A total of three studies provided data on SEP-2 and SEP-3. Subgroups for improvement in SEP-2 on the basis of follow-up at weeks 4, 7, and 12 demonstrated similar results (P-interaction = 0.43). Overall, SEP-2 did not significantly improve in the intervention group (RR: 1.16 [95% CI: 0.93, 1.45], p-value = 0.18; Figure 4). Subgroups for improvement in SEP-3 were also made at 4-, 7- and 12-week follow-ups, and demonstrated similar results (P-interaction = 0.20; Figure 5). Pooled analysis represented a significant improvement in SEP-3 from baseline in the treatment group versus control group (RR: 2.07 [95% CI: 1.49, 2.89], I² = 70%, p-value = 0.0001).

Figure 4.

Effect of Li-ESWT on improvement in EHS-2.

Figure 5.

Effect of Li-ESWT on improvement in SEP-3.

4. Discussion

This meta-analysis of 12 RCTs, including a total of 882 men with vasculogenic erectile dysfunction, demonstrated a statistically significant improvement in IIEF-EF score i.e., International Index of Erectile Function (an improvement from baseline as well as MCID) and EHS i.e., Erection Hardness Score (patients with EHS ≥ 3) after low-intensity extracorporeal shockwave therapy in comparison to men undergoing sham therapy.

Our study expands on the previous meta-analysis by Dong et al. [31]. Two previous meta-analysis have been published by Lu et al. (2017) and Man and Li (2018) which included heterogeneous patient populations and were not confined to the inclusion of randomized controlled trials only [32,33]. Clavijo et al. were the first to publish on a homogenous population and included only RCTs (level 1 A evidence) however analyzed only the change in IIEF-score outcome [34]. Despite these limitations, their work was of great value in this arena. In the present meta-analysis, we opted to incorporate only RCTs because this study design methodology provides the highest level of scientific evidence. Studies based on patient populations with erectile dysfunction associated with other underlying pathological conditions (e.g., Peyronie’s disease, chronic pelvic pain syndrome, diabetes mellitus) were not included. Those studies which included patients with ED due to a history of radical prostatectomy were excluded. Our analysis was unable to report on objective parameters like ultrasound Doppler findings because they were not uniformly reported by the RCTs.

Since the use of low-intensity extracorporeal shockwave therapy for erectile dysfunction is not fully explored and tested to its fullest, the mechanisms by which Li-ESWT acts to improve ED symptoms are yet to be fully understood. Animal studies have substantially explained that shock waves cause microtrauma and mechanical trauma that stimulate the release of growth factors, such as vascular endothelial growth factor, which lead to angiogenesis that may improve blood flow [35]. Scroppo et al. demonstrated that low-intensity extracorporeal shockwave therapy treatment promotes neovascularization of the functional arteries in patients affected by vasculogenic ED [36]. Another potential downstream effect of Li-ESWT could be the upregulation of neuronal or endothelial nitric oxide synthase [37,38]. An increase in baseline levels of nitric oxide, a known penile smooth muscle relaxant normally involved in penile tumescence, could be responsible for the improved erectile function seen after Li-ESWT [39]. Shockwave therapy has also been postulated to stimulate the recruitment and activation of stem cells in a variety of tissues including skeletal muscle and skin flaps and in a rat model of pelvic neurovascular injury leading to angiogenesis, tissue restoration, and nerve regeneration [40,41]. Sokolakis et al. demonstrated a decrease in age and diabetes-induced sympathetic hyperactivity in the corpus cavernosum via an increased expression of α2 adrenergic receptors with a parallel decrease in the expression of α1 adrenergic receptors because of Li-ESWT [42]. Based on these findings, it is suggested that low-intensity extracorporeal shockwave therapy could increase blood flow and endothelial function in the penis thereby improving erectile function. Despite initial enthusiasm surrounding LiESWT due to promising early results, it has become evident that it does not offer a definitive solution for ED. Over time, its effects tend to diminish, and the observed changes in the International Index of Erectile Function (IIEF) score are not consistently robust. It is essential to recognize that neither oral therapy nor LiESWT address the underlying pathophysiological mechanisms of ED comprehensively. Both modalities have their limitations. However, upon closer examination, the drawbacks associated with LiESWT appear to be more significant compared to oral therapy.

Moderate heterogeneity was observed in the mean EHS score (I² = 65%) that could not be attributed to any single study on sensitivity analysis. It did not decrease on the omission of studies and hence was distributed across the eight studies. A plausible reason for this might be the use of different treatment regimens. Amongst the eight RCTs that reported mean EHS outcome, four applied the intervention at 5 sites (Vardi et al., Srini et al., Kitrey et al., Yee et al.), two applied on 3 sites (Kim et al., Yamacake et al.), one on 6 sites (Olsen et al.) and one on 4 sites (Vinay et al.) of the penis. The greatest heterogeneity in treatment effects was noted amongst studies including patients who were non-responsive to PDE5i (I² = 81%). This can be attributed to the use of a different number of shocks; Vinay et al. administered 5000 shocks per treatment session with only one session per week. While other RCTs were administered between 1500 and 3000 shocks.

Similarly, for change in IIEF-EF Score heterogeneity (I² = 93%) did not decrease on sensitivity analysis. This is possibly a result of three different sources of ESWT used amongst the eight RCTs that reported Change in IIEF-EF Score. Sramkova et al. and Fojecki et al. used a piezoelectric device, while Vinay et al. were the only ones to use an electromagnetic source and the remaining five RCTs used an electrohydraulic source. Our analysis identified a mean IIEF-EF score of 90% which after sensitivity analysis dropped to 63%. An increase in heterogeneity was observed in this updated meta-analysis pertaining to different treatment protocols. Five out of the nine RCTs with a mean IIEF-EF score used 6000–1500 shocks/session. Chung et al. and Sramkova et al. administered 3000 and 6000 shocks/session and shock wave intensities used were 0.16 and 0.25 mJ/mm respectively. One of the studies, Srini et al., did not report wave intensity at all.

The use of low-intensity extracorporeal shockwave therapy for long-term clinical management of ED can be an invaluable addition to the currently available treatment options. Initial screening by penile ultrasound must be carried out to ensure only men with vasculogenic erectile dysfunction are included and accurate documentation of comorbidities like diabetes and depression at the start of treatment must be done to rule out other causes of ED. Studies with PDE5i washout periods are needed to ensure the results are not influenced by prior treatment and determine the independent efficacy of Li-ESWT. Future randomized controlled trials with standardized and detailed treatment protocols including the number of treatment sessions, number of shocks, energy intensity, type of probe, and site of administration are required. Additional studies in carefully categorized populations, including diabetic men and men who have had renal transplants, and men with severe, mild, or moderate ED, are necessary to properly evaluate which population may maximally benefit from low-intensity extracorporeal shockwave therapy. Dose-response studies, like Kayvianakis et al., in the future will aid in assessing the efficiency of an optimum treatment protocol [43]. Large-scale and multicentric randomized sham-controlled trials with longer follow-ups are necessary to fully elucidate concerns regarding the long-term efficacy and delayed adverse effects, hence determining the sustainability of the benefit of Li-ESWT for the treatment of erectile dysfunction.

The key findings of the study by Yao et al. suggest that Low-Intensity Extracorporeal Shock Wave Therapy (LIESWT) is effective in improving erectile function in men with erectile dysfunction. The meta-analysis synthesized evidence from 16 randomized controlled trials and found that LIESWT led to significant improvements in erectile function compared to placebo or sham therapy. Additionally, like our study, the study highlights the potential of LIESWT as a noninvasive and promising treatment option for erectile dysfunction [44]. We have incorporated longer follow-up periods in the included trials allowing for a better understanding of the durability and sustainability of the treatment effects over time. We have also conducted subgroup analysis based on follow up periods, PDE5i-responders, kidney transplant recipients, etc. helping to assess the potential impact of it.

It is essential to establish standardized treatment protocols for low-intensity extracorporeal shockwave therapy in the management of erectile dysfunction. This entails determining the prime number of treatment sessions, intensity and quantity of shocks, energy intensity, probe type, and administration site. By achieving consistency in treatment protocols, researchers can facilitate better comparisons between studies and enhance the reproducibility of results. Rigorous screening measures, such as penile ultrasound, should be incorporated to ensure the inclusion of men with vasculogenic erectile dysfunction, while carefully categorized populations, including diabetic men, renal transplant recipients, and individuals with varying severity levels of ED, should be examined to assess the efficacy and applicability of Li-ESWT in these specific groups. Large-scale, multicentric randomized controlled trials with extended follow-up periods are imperative to evaluate the long-term efficacy and safety of Li-ESWT. Additionally, integrating objective parameters, like penile Doppler ultrasonography, will provide a comprehensive understanding of the underlying etiology of erectile dysfunction in response to Li-ESWT. Dose-response studies and incorporating washout periods for phosphodiesterase type 5 inhibitors will help determine the optimal treatment protocol and assess the independent efficacy of Li-ESWT. Furthermore, it is crucial to evaluate low-intensity extracorporeal shockwave therapy in diverse patient populations, including those with comorbidities and varying degrees of ED severity, to understand its applicability and benefits across different clinical scenarios. Multidisciplinary collaboration among researchers, clinicians, and industry experts will play a pivotal role in advancing low-intensity extracorporeal shockwave therapy research, fostering innovation, and generating robust evidence for optimal treatment strategies in the future.

Our meta-analysis has several notable limitations that should be acknowledged. Firstly, the majority of the included randomized controlled trials (RCTs) had small sample sizes, with the largest study including only 135 men. Moreover, the follow-up periods varied and were relatively short, ranging from 1 month to 12 months, and later outcomes were not consistently reported in these RCTs. This limited follow-up duration may not fully capture the long-term effectiveness of low-intensity extracorporeal shockwave therapy for erectile dysfunction.

Furthermore, the original studies lacked objective parameters, such as penile Doppler ultrasonography, which could provide valuable insights into the underlying causes of erectile dysfunction. The absence of such objective diagnostic tools may limit the accuracy of the etiological diagnosis in these studies.

Another challenge lies in the variability of treatment protocols across the included RCTs. There were variations in the types of lithotripters used, treatment durations, and the number and intensity of shockwaves applied. This heterogeneity makes it difficult to establish an optimal and standardized treatment protocol for erectile dysfunction using Li-ESWT.

Additionally, although the studies were randomized, it should be noted that some participants did not complete the trial. This can introduce bias and limit the generalizability of the findings, as the data only represent the subset of participants who completed the study, potentially leading to misleading conclusions regarding the efficacy of low-intensity extracorporeal shockwaves, if dropouts were due to the intervention itself.

The study’s findings underscore several crucial limitations in current research on erectile dysfunction (ED) and sexual dysfunction. Firstly, there is a pressing need for larger and more diverse participant samples to enhance statistical power and ensure the applicability of findings across diverse populations. Secondly, extending follow-up periods in future studies is imperative for a comprehensive understanding of the long-term efficacy and potential side effects of therapies. Thirdly, standardizing treatment protocols is essential to facilitate comparisons between studies and draw more definitive conclusions. Additionally, incorporating objective diagnostic tools, such as penile Doppler ultrasonography, can provide more precise insights into the underlying causes of ED. Broadening the discussion beyond ED to encompass various medical conditions, like celiac disease, would offer a comprehensive understanding of their impact on sexual function, highlighting the importance of a holistic approach to sexual health. Furthermore, identifying new research areas, particularly regarding the relationship between autoimmune diseases and sexual dysfunction, could pave the way for targeted interventions and support for affected individuals.

Considering these limitations, it is important to interpret the findings of our meta-analysis with caution and recognize the need for larger, well-designed randomized controlled trials with longer follow-up periods and standardized treatment protocols. Incorporating objective diagnostic tools and ensuring high participant retention rates would enhance the robustness and applicability of future studies investigating the efficacy of low-intensity extra shock wave therapy for the treatment of erectile dysfunction.

5. Conclusion

This meta-analysis of the available randomized controlled trials presents strong evidence supporting the effectiveness of low-intensity extracorporeal shockwave in improving erectile dysfunction. The results demonstrate a significant improvement in both the International Index of Erectile Function-Erectile Function (IIEF-EF) scores and the Erection Hardness Score (EHS) for men who received Li-ESWT compared to those who underwent sham therapy. These findings highlight the positive impact of low-intensity extracorporeal shockwave therapy on erectile dysfunction and emphasize its potential as a promising treatment option for men experiencing this condition.

Funding Statement

This article was not funded.

Author contributions

Conceptualization, data curation, and project administration were carried out by KF. Supervision was carried out by AMR. Formal analysis of data was carried out by ZA, RA and SIA. Formal analysis, methodology, and software were carried out by ZA, RA and SIA. Writing the original draft was carried out by ZA, AN, SIA, RA, FN, and SZ. Writing, reviewing, and editing were carried out by AMR. Visualization and validation were carried out by AMR.

Disclosure statement

Financial disclosure

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The corresponding author certifies, on behalf of all the authors listed in the manuscript, that the information presented is accurate and true.

Writing assistance disclosure

No funded writing assistance has been used in the creation of the manuscript.