Goldstein SW. et al., 2024: Randomized trial of low intensity shockwave therapy for erectile dysfunction utilizing grayscale ultrasound for analysis of erectile tissue homogeneity/inhomogeneity.
Sue W Goldstein 1, Noel N Kim 2, Irwin Goldstein 1 3
1San Diego Sexual Medicine, San Diego, CA, USA.
2Institute for Sexual Medicine, San Diego, CA, USA.
3Sexual Medicine, University of California San Diego Health East Campus, San Diego, CA, USA.
Abstract
Background: Electrohydraulic shockwave devices have been Food and Drug Administration-cleared for improved blood flow and connective tissue activation and have been used to treat erectile dysfunction (ED). In this study, the main focus was to evaluate improvement in erectile tissue quality after low intensity shockwave therapy (LiSWT).
Methods: A single-blind, sham-controlled, randomized, prospective study, was performed in men with ED naïve to shockwave or radial ballistic pressure wave therapy. Participants were randomized 1:2 to simulated (sham) or active LiSWT treatment. After simulated treatments, participants in the Sham Arm were converted to active LiSWT, while participants initially in the Active Treatment Arm received no further treatment. Assessments were performed at baseline and two follow-up visits. Subjective parameters of erectile function (EF) were assessed by total and EF domain scores of the International Index of Erectile Function (IIEF) and sexual encounter profile (SEP). Objective parameters of penile erection were measurements of hypoechoic areas in images obtained by grayscale ultrasound (GUS) with high resolution 15.4 MHz probe and cavernosal artery peak systolic velocity (PSV) and end diastolic velocity (EDV) by color duplex Doppler ultrasound (DUS). Outcome measures for erectile and urinary function were also obtained.
Results: Simulated LiSWT did not significantly change any assessment parameter. Sham Arm participants who converted to active LiSWT had significantly increased mean IIEF total (P=0.02) and IIEF-EF scores that approached statistical significance (P=0.06), relative to baseline. Similarly, at the end of the study, Active Treatment Arm participants had significantly increased mean IIEF total (P=0.02) and IIEF-EF scores that approached statistical significance (P=0.07), relative to baseline. Additionally, at the end of the study, SEP3 success rates (erection lasting long enough for successful intercourse) approached statistical significance when Sham Arm participants were converted to active LiSWT (P=0.08) and reached statistical significance in the Active Treatment Arm (P=0.049). GUS assessments by visual grading were significantly correlated to IIEF-EF score (P=0.002) and were significantly increased relative to baseline in the Active Treatment Arm at follow-up Assessment 1 (P=0.03) and Assessment 2 (P=0.04). The greatest reduction in hypoechoic area after LiSWT occurred in the proximal penile shaft. EDV was also significantly reduced in the Active Treatment Arm at follow-up Assessment 1 (P=0.04) and Assessment 2 (P=0.04). LiSWT also resulted in improved prostate symptom scores, approaching significance in the Active Treatment Arm (P=0.055) with no changes in prostate-specific antigen. Treatment-related adverse events were limited and transient.
Conclusions: In this prospective trial, LiSWT was safe and efficacious for erectile symptoms using GUS imaging as a novel, non-invasive method to assess improvements in corporal veno-occlusive function. Improved veno-occlusion and reduced hypoechoic area demonstrated by GUS imaging suggest that LiSWT decreases connective tissue content in penile erectile tissue. Lower urinary tract symptoms also improved with LiSWT.
Transl Androl Urol. 2024 Oct 31;13(10):2246-2267. doi: 10.21037/tau-24-338. Epub 2024 Oct 28.
PMID: 39507857 FREE PMC ARTICLE
Comments 1
The article investigates the efficacy of low-intensity shockwave therapy (LiSWT) for erectile dysfunction (ED) with a specific focus on the use of grayscale ultrasound (GUS) as a novel assessment tool. The study was conducted on men with ED who had not previously received shockwave treatments, using a randomized (1:2), sham-controlled, and single-blind design. Grayscale ultrasound was employed to analyze erectile tissue homogeneity and inhomogeneity, providing objective visual grading alongside traditional subjective measures like the International Index of Erectile Function (IIEF).
Participants underwent a four-week screening period during which their medical history was assessed, and baseline erectile function was measured using grayscale ultrasound (GUS) and color duplex Doppler ultrasound (DUS). For this purpose, the participants were administered an intracavernosal injection of vasoactive agents, papaverine (30 mg), phentolamine (1–10 mg), prostaglandin E1 (0–60 mcg per 0.1–0.5 mL) to achieve a sustained pharmacologic erection, 3–4 out of 4 on the Erection Hardness Scale (EHS) with redosing as needed. Ultrasound was performed using a high-resolution probe (Aixplorer 15.4 mHz transducer). For GUS, three different gain settings 45%, 55%, and 65% with the dynamic range set at 70 dB were used. Images were captured in the axial plane at the proximal, mid, and distal penile shaft. The GUS erectile tissue homogeneity/ inhomogeneity for each area of the penile shaft was visually graded immediately after image acquisition by investigators and graded
accordingly:
The LiSWT treatment protocol involved the use of a specific shockwave device, with participants receiving either active or sham treatments. Shockwaves were generated by an electrohydraulic shockwave device SoftWave TRT/UroGold 100MTS utilizing the parabolic applicator OP 155. Due to the absence of a concentrated focus, a 14 mm wide shockwave was delivered to the erectile tissue with up to 30 mm penetration. The initial energy flux density setting was 0.12 mJ/mm2. For simulated treatment, a high-quality recording of shockwave sounds was played through a Bluetooth speaker. Since participants were naïve to acoustic wave therapy, there were no expectations of perceiving sensation from the applicator during simulated (no energy) treatment.
Clinical assessments were conducted at baseline and follow-up visits, collecting data on subjective and objective measures of erectile function. The results indicated significant improvements in erectile tissue homogeneity and erectile function scores (IIEF: 16 vs 11,5) in participants receiving active treatment compared to those in the sham group.
Key findings indicated that active LiSWT led to significant improvements in erectile function as assessed by IIEF scores and GUS grading, reflecting enhanced erectile tissue health. The study revealed that GUS could effectively detect changes in cavernosal tissue composition, highlighting its potential as a sensitive measure of corporal veno-occlusive function. The results suggested that LiSWT not only improved erectile function but also positively influenced the structural integrity of erectile tissue, supported by increased stem cell activation and reduced fibrosis.
Despite limitations due to a small sample size (N=35) influenced by the COVID-19 pandemic, the study underscores the utility of GUS in evaluating treatment outcomes for ED. The findings advocate for the inclusion of GUS in future research and clinical practice as an objective measure to assess the effects of LiSWT on erectile tissue. The article emphasizes the biological mechanisms behind LiSWT, supported by animal studies, and discusses the potential for LiSWT as a safe and effective treatment for ED. There is no doubt, that such studies should be continued by other groups. However, it might be still unclear, whether patients really need to be treated under artificial erection.
When applying low-intensity shockwave therapy (LiSWT), it is typically recommended to perform the treatment while the patient is in a relaxed state. This usually means that an artificial erection is not necessary for the application of LiSWT itself. The therapy primarily aims to stimulate the erectile tissue through mechanical waves, promoting biological responses such as increased blood flow and the activation of stem cells.
However, having an artificial erection during the evaluation phase, such as when conducting ultrasound assessments, can provide valuable insights into the structural and functional changes in the erectile tissue post-treatment. It allows for better visualization of the effects of LiSWT on the cavernosal tissue and can help correlate treatment outcomes with the observed changes in erectile function.
In summary, while artificial erection is not required during the actual application of LiSWT, it can be beneficial for assessment and evaluation purposes to ensure comprehensive understanding and monitoring of treatment efficacy.
Jens Rassweiler