Low-intensity Extracorporeal Shockwave Therapy Research Articles

Low-intensity extracorporeal shock wave therapy for Peyroniès disease: a systematic review and meta-analysis.

A systematic review of the evidence was conducted to assess the efficacy of low-intensity extracorporeal shock wave therapy (LI-ESWT) for patients with Peyronie`s Disease (PD). A comprehensive search of the Cochrane Registry, PubMed and Embase databases was conducted to identify all controlled trials, including randomised controlled trials (RCTs), cohort studies and case-control studies, focusing on the efficacy of LI-ESWT in treating PD, and published before February 2023. The size of plaques, curvature deviation, visual analog scale [VAS] and International Index of Erectile Function (IIEF) were the most commonly used tool to evaluate the treatment effectiveness of LI-ESWT. There were 7 studies including 475 patients from 1999 to 2023. The meta-analysis of the data revealed that LI-ESWT could considerably enhance the proportion of men experiencing a reduction in penile plaques (RD 0.27, 95% CI: 0.04-0.50, P = 0.02), improvement in penile curvature (RD: 0.13; 95% CI, 0-0.26; p = 0.05), alleviation of pain (RD 0.22, 95% CI: 0.01-0.42, P = 0.04), and complete remission (RD 0.38, 95% CI 0.23-0.52, P < 0.00001). However, there were no significant differences in improvement of sexual function (MD: 1.44; 95% CI, -3.10-5.97; p = 0.53) between LI-ESWT and the placebo group. According to these studies, LI-ESWT has the potential to decrease plaque size and improve penile curvature or pain in men with PD. The publication of robust evidence from additional well-designed long-term multicenter randomized controlled trials would provide more confidence regarding use of these devices in patients with PD.

Pharmacological Treatments for Erectile Dysfunction in Diabetic Patients: Efficacy, Safety, and Emerging Therapies

Men with diabetes mellitus, particularly those with type 2 diabetes (T2DM), are known to experience erectile dysfunction (ED), a condition whose prevalence has risen to 75% in recent years. The pathophysiology of ED in diabetic patients involves vascular impairment, neuropathy, hormonal dysregulation, and chronic hyperglycemia, all of which contribute to endothelial dysfunction, reduced nitric oxide availability, and nerve damage. Phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil, are the first-line pharmacological treatments for ED, though their efficacy is reduced in diabetic patients due to the extent of vascular and neurological damage. Other treatments, including testosterone replacement therapy (TRT), intracavernosal injections, and vacuum erection devices (VEDs), provide alternatives for patients unresponsive to PDE5 inhibitors. Emerging therapies such as low-intensity extracorporeal shockwave therapy (LI-ESWT) and regenerative medicine approaches, including stem cell and platelet-rich plasma (PRP) injections, show potential in improving erectile function in diabetic patients. Glycemic control plays a critical role in both preventing ED and enhancing the efficacy of treatments by improving vascular function and reversing nerve damage. This review was conducted through an extensive analysis of current literature on pharmacological and emerging treatments for ED in diabetic patients. In conclusion, integrating traditional pharmacotherapy with emerging treatments and emphasizing glycemic control holds promise for optimizing ED management in diabetic patients. Keywords: Erectile Dysfunction (ED), Diabetes Mellitus (T2DM), Phosphodiesterase Type 5 (PDE5) Inhibitors, Testosterone Replacement Therapy (TRT), Glycemic Control

Retrospective analysis of the efficacy of low-intensity extracorporeal shock wave therapy on young and middle-aged patients with erectile dysfunction responsive to PDE5Is: reducing the use of PDE5Is.

Low-intensity extracorporeal shock wave therapy (Li-ESWT) is a new method for treating erectile dysfunction (ED), but there are no standards yet for its indications. The study aimed to suggest the early clinical efficacy of Li-ESWT and explore its related factors in young and middle-aged patients with ED who responded to phosphodiesterase type 5 Inhibitors (PDE5Is). Data from 61 patients with ED who had previously responded to oral PDE5Is and subsequently underwent Li-ESWT were collected. This included information on age, body mass index, total testicular volume, sex hormones, as well as IIEF-EF scores before treatment and at 1, 3, and 6months after treatment. The treatment regimen involves a weekly session for four consecutive weeks, with each session administering 5000 shock wave pulses. Linear regression analysis was utilized to identify factors associated with the efficacy of Li-ESWT treatment. Additionally, the improvement in different severity groups of ED before and after treatment, along with their IIEF-EF scores, was compared. Li-ESWT was more targeted and effective for young and middle-aged patients with erectile dysfunction who responded to PDE5Is. The age of enrolled patients ranges from 22 to 53years old, and the IIEF-EF scores at 1month, 3months, and 6months after treatment were compared to baseline for efficacy assessment, showing significant improvements (P < .0001) in all instances. Linear regression analysis using baseline data revealed predictive factors associated with treatment efficacy: treatment efficacy was negatively correlated with baseline IIEF-EF scores (t = -2.599, P = .013) and positively correlated with baseline LH levels (t = 2.170, P = .036). Given the considerable cost of Li-ESWT treatment and the emphasis on treatment continuity, we hope to identify the most suitable candidates for Li-ESWT therapy, thereby optimizing its application. Our findings provide a better solution for nonelderly ED patients who are responsive to PDE5Is. This study was limited by our sample size and follow-up time. After 3months of Li-ESWT, the IIEF-EF score gradually stabilizes and short-term maintenance of PDE5Is medication increases the responsiveness to shock wave therapy.

Safety of low-intensity extracorporeal shock wave therapy in prostate disorders: in vitro and in vivo evidence.

Recent evidence suggests that low-intensity extracorporeal shock wave therapy (Li-ESWT) is a promising treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its safety in pelvic organs, particularly prostate tissues and cells, remains unclear. The current study evaluates the risks of prostate cell damage or oncogenesis following the administration of Li-ESWT for prostatitis. To this end, a robust in vitro model (Cell Counting Kit-8 [CCK-8] assay, clone formation assay, cell scratch assay, lactate dehydrogenase [LDH] release assay, flow cytometry, and immunoblotting assay) was designed to examine the effects of Li-ESWT on cell proliferation, clonogenicity, migration, membrane integrity, and DNA damage. Exome sequencing of Li-ESWT-treated cells was performed to determine the risk of carcinogenesis. Furthermore, an in vivo rat model ( n = 20) was employed to assess the effects of Li-ESWT on cancer biomarkers (carcinoembryonic antigen [CEA], Ki67, proliferating cell nuclear antigen [PCNA], and gamma-H2A histone family member X, phosphorylation of the H2AX Ser-139 [ γ -H2AX]) in prostate tissue. Based on our findings, Li-ESWT promotes cellular growth and motility without inducing significant cell membrane or DNA damage or alterations. Genetic analyses did not demonstrate an increase in mutations, and no damage to prostate tissue or upregulation of cancer biomarkers was detected in vivo. This comprehensive in vitro and in vivo assessment confirms the safety of Li-ESWT in managing prostate disorders.

Microenergy shockwave therapies for female stress urinary incontinence.

Stress urinary incontinence (SUI) is one of the pelvic floor disorders affecting tens of million of women worldwide. In general, non-surgical options have relatively limited efficacy. The most effective treatment is mid-urethral sling surgery which carries substantial risks of perioperative and postoperative complications. Regenerative therapy with the injection of several types of stem cells and stem cell products is promising but further investigation is needed before clinical implementation can be considered. In recent years, the application of microenergy therapy as a non-invasive treatment for SUI has received increasing attention. Preclinical animal studies of these models have demonstrated that low-intensity extracorporeal shockwave therapy (Li-ESWT) and microenergy acoustic pulse (MAP) therapy are capable of regenerating urethral sphincter tissue and pelvic floor muscles leading to improved urinary continence. One pilot clinical trial with Li-ESWT also reported improved quality of life in women with SUI as well as the symptoms. The objective of this review is to summarize the potential mechanisms associated with Li-ESWT and MAP therapies of SUI: (I) activation of tissue-resident stem cells; (II) regeneration of musculature in the urethra and pelvic floor; (III) improvement in biomechanical property of pelvic floor muscles; (IV) modulation of cellular signaling pathways. Further studies of the molecular mechanisms, optimal treatment dosage and schedule, and potential long-term side effects are needed to provide this non-invasive regenerative therapy for millions of women with SUI.

Promising Experimental Treatment in Animal Models and Human Studies of Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain Syndrome (IC/BPS) remains a mysterious and intricate urological disorder, presenting significant challenges to healthcare providers. Traditional guidelines for IC/BPS follow a hierarchical model based on symptom severity, advocating for conservative interventions as the initial step, followed by oral pharmacotherapy, intravesical treatments, and, in refractory cases, invasive surgical procedures. This approach embraces a multi-tiered strategy. However, the evolving understanding that IC/BPS represents a paroxysmal chronic pain syndrome, often involving extravesical manifestations and different subtypes, calls for a departure from this uniform approach. This review provides insights into recent advancements in experimental strategies in animal models and human studies. The identified therapeutic approaches fall into four categories: (i) anti-inflammation and anti-angiogenesis using monoclonal antibodies or immune modulation, (ii) regenerative medicine, including stem cell therapy, platelet-rich plasma, and low-intensity extracorporeal shock wave therapy, (iii) drug delivery systems leveraging nanotechnology, and (iv) drug delivery systems assisted by energy devices. Future investigations will require a broader range of animal models, studies on human bladder tissues, and well-designed clinical trials to establish the efficacy and safety of these therapeutic interventions.

Effects of low-intensity extracorporeal shock wave on bladder and urethral dysfunction in spinal cord injured rats.

To investigate the effects of low-intensity extracorporeal shock wave therapy (LiESWT) on bladder and urethral dysfunction with detrusor overactivity and detrusor sphincter dyssynergia (DSD) resulting from spinal cord injury (SCI). At 3 weeks after Th9 spinal cord transection, LiESWT was performed on the bladder and urethra of adult female Sprague Dawley rats with 300 shots of 2Hz and an energy flux density of 0.12mJ/mm2, repeated four times every 3 days, totaling 1200 shots. Six weeks postoperatively, a single cystometrogram (CMG) and an external urethral sphincter electromyogram (EUS-EMG) were simultaneously recorded in awake animals, followed by histological evaluation. Voiding efficiency significantly improved in the LiESWT group (71.2%) compared to that in the control group (51.8%). The reduced EUS activity ratio during voiding (duration of reduced EUS activity during voiding/EUS contraction duration with voiding + duration of reduced EUS activity during voiding) was significantly higher in the LiESWT group (66.9%) compared to the control group (46.3%). Immunohistochemical examination revealed that fibrosis in the urethral muscle layer was reduced, and S-100 stained-positive area, a Schwann cell marker, was significantly increased in the urethra of the LiESWT group. LiESWT targeting the urethra after SCI can restore the EUS-EMG tonic activity during voiding, thereby partially ameliorating DSD. Therefore, LiESWT is a promising approach for treating bladder and urethral dysfunction following SCI.

Patient out-of-pocket costs for guideline-recommended treatments for erectile dysfunction: a medicare cost modeling analysis.

Patient out-of-pocket (OOP) cost represents an access barrier to erectile dysfunction (ED) treatment. We determined OOP cost for men with ED covered by Fee-for-Service Medicare. Coverage policies were obtained from the Medicare Coverage Database for treatments recommended by the 2018 American Urological Association (AUA) guidelines. OOP cost was retrieved from the 2023 Centers for Medicare & Medicaid Services Final Rule. OOP cost for treatments without Medicare coverage were extracted from GoodRx® or literature and inflated to 2022 dollars. Annual prescription costs were calculated using the published estimate of 52.2 yearly instances of sexual intercourse. Medicare has coverage for inflatable penile prostheses (IPP; strong recommendation), non-coverage for vacuum erection devices (VED; moderate recommendation) and phosphodiesterase type-5 inhibitors (PDE5i; strong recommendation), and no policies for intracavernosal injections (ICI; moderate recommendation), intraurethral alprostadil (IA; conditional recommendation), or low-intensity extracorporeal shock wave therapy (ESWT; conditional recommendation). Annual IA prescription is most costly ($4022), followed by ICI prescription ($3947), one ESWT course ($3445), IPP ($1600), PDE5i prescription ($696), and one VED ($213). PDE5i and IPP, both strongly recommended by AUA guidelines, are associated with lower OOP cost. Better understanding of patient financial burden may inform healthcare decision-making.

(101) SHOCKWAVE THERAPY FOR THE TREATMENT OF POSTPARTUM STRESS URINARY INCONTINENCE: A PILOT STUDY

Abstract Introduction Stress urinary incontinence (SUI) is estimated to affect approximately 15% of adult women. Low-intensity extracorporeal shock wave therapy (Li-ESWT) is a form of electrohydraulic acoustic shockwave that has been shown to be effective in animal models of SUI. The Urogold100® is a Li-ESWT device that is FDA-cleared for improving blood flow, connective tissue activation, and pain relief, and it has been shown in multiple studies to be effective for mild to moderate erectile dysfunction and chronic pelvic pain in both men and women. While Li-ESWT has been investigated for related urologic conditions, minimal research exists as to its potential effectiveness for SUI in women. Objective Our aim was to evaluate the effectiveness of Li-ESWT for women with postpartum stress urinary incontinence in a pilot study. Methods Email recruitment was carried out in a single sexual medicine practice. Four women underwent weekly treatments with Li-ESWT for 4-6 weeks. All patients were postpartum women between ages 43-55. Treatment specifics included 1000 shocks at 2.5 Hz (initial visit) and 3.0 Hz (subsequent visits) distributed over the perineum and urethral opening. Energy level was based on patient tolerance, beginning with 0.06 Mj/mm2 and increased up to 0.08 Mj/mm2 for subsequent visits. Evaluation measures included the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Bladder Diary, both administered prior to treatment initiation and after treatment completion. The ICIQ-SF allowed patients to self-assess their urine leakage over the past several weeks (amount and frequency) while the Bladder Diary required patients to record specific leakage incidences throughout a single day. Results Prior to treatment initiation, patients reported 1-3 small daily urine leaks via the NIDDK Bladder Diary. All patients either improved or remained the same in this assessment post-treatment; all patients reported 1 small daily leak after treatment completion. Results from the subjective ICIQ-SF varied: 1 patient reported worsening from 1 daily leak to 2-3 daily leaks, which she attributed to increased water intake. Two patients reported improvements (several daily leaks to 1 weekly leak; several daily leaks to 2-3 weekly leaks). One patient reported no change. Subjective reporting from patients indicated 3 of the 4 felt the treatment was improving their symptoms, and the fourth patient reported no changes. Conclusions Our pilot study indicates that 3 of 4 patients showed improvements in their objective Bladder Diary recordings with reduced frequency of urine leakage, and 2 of 4 patients noted improvements in their subjective ICIQ-SF reporting. 3 of 4 provided positive verbal feedback as well. Despite the limited sample size, the improvements seen in the objective leakage frequency recordings are encouraging findings that warrant future investigation in a larger cohort. Given the noninvasive nature, ease of use, and high patient tolerability of Li-ESWT, this treatment modality should be considered for investigation in a larger cohort with the goal of relieving symptoms of SUI. Disclosure No.

Indirect assessment of low-intensity shockwave therapy's energy density and pulse frequency for erectile dysfunction: a systematic review, bayesian network meta-analysis and meta-regression.

Shockwaves are thought to activate regenerative and angiogenic pathways, providing a possible therapeutic benefit for patients with erectile dysfunction. This study aimed to analyze the effectiveness of low-intensity extracorporeal shockwave therapy energy density and pulse frequency. In May 2022, a systematic search of online databases was performed to identify randomized clinical trials related to low-intensity extracorporeal shockwave therapy in erectile dysfunction. Eligible articles compared low-intensity extracorporeal shockwave therapy to controls or sham procedures. A Bayesian framework with 200,000 Markov chains was performed. We included a total of 1272 patients from 18 studies. The energy flux density measured in joules included 0.09 mJ/mm2 (mean difference 3.2 IIEF [95% CrI 2.8, 3.6]), 0.15 mJ/mm2 (mean difference 4.9 IIEF [95% CrI 2.8, 7.2]) and 0.20 mJ/mm2 (mean difference 1.2 IIEF [95% CrI 0.11, 2.3]). Of these, 0.15 mJ/mm2 had the greatest ranking (SUCRA = 0.983) compared with placebo. When analyzed by pulse frequency, significant increases were found in 500 pulses/session (mean difference 2.5 IIEF [CrI 1.9, 3.2]), 1500 pulses/session (mean difference 4.6 IIEF [95% CrI 3.9, 5.4]) and > 3000 pulses/session (mean difference 3.1 IIEF [95% CrI 2.1, 4.2]). Of these, 1500 pulses/session had the highest SUCRA, at 0.996. Our network meta-analysis suggests that low-intensity extracorporeal shockwave therapy is an effective intervention for erectile dysfunction, as measured by increases in the IIEF-EF. Sessions featuring 1500 pulses and an energy flux density of 0.15 mJ/mm2 appear to be the most effective.

Conservative treatment of Peyronie's disease: a guide.

To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease. A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic. Peyronie's disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified. Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required.

Androgens and erectile dysfunction: from androgen deficiency to treatment.

Androgens play important roles in regulating the growth and development of the male reproductive system and maintaining libido and erectile function. The specific mechanisms by which androgen deficiency leads to erectile dysfunction (ED) are not yet fully understood. To understand the mechanisms and treatment of androgen deficiency-related ED. A literature search in the past 10years was conducted in PubMed and Google Scholar to determine the effects of androgen deficiency on erectile function and the treatment of androgen deficiency. Androgen deficiency can be caused by hypothalamic-pituitary lesions and injuries, testicular-related diseases and injuries, endocrine and metabolic disorders, the side effects of medication, and age. Androgen deficiency can lead to ED by inhibiting the NOS/NO/cGMP pathway (nitric oxide synthase/nitric oxide/cyclic guanosine monophosphate) and altering the expression of ion channel proteins, as well as by inducing oxidative stress, death, and fibrosis in penile corpus cavernosum cells. Testosterone replacement therapy is effective at improving the serum testosterone levels and erectile function in patients with androgen deficiency. For patients who need to maintain a low androgenic state, erectile function can be improved by lifestyle changes, treatment with phosphodiesterase type 5 inhibitors, low-intensity extracorporeal shock wave therapy, and stem cell therapy. Androgen deficiency can affect the structure and function of the penile corpus cavernosum, leading to ED. Areas of further study include how androgen replacement therapy can improve erectile function and how to improve the maintenance of erectile function in patients with hypoandrogenic status.

Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Detrusor Hyperactivity with Impaired Contractility via Transient Potential Vanilloid Channels: A Rat Model for Ovarian Hormone Deficiency.

This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca2+ channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.

LOW-INTENSITY SHOCKWAVE TREATMENT FOR NEUROGENIC BLADDER WITH CHRONIC URINE RETENTION - CASE REPORT

We present a case of neurogenic bladder accompanied by chronic urine retention in a patient diagnosed with multiple sclerosis (MS). This condition was effectively managed by low-intensity shockwave therapy (Li-ESWT). Low-intensity focused shockwave therapy (Li-ESWT) is becoming increasingly important in the treatment of urological problems. This case study investigates the feasibility and efficacy of using Li-ESWT to reduce post-void residual volume in persons with neurogenic bladder, representing the first examination of its sort. Bladder dysfunction (BD) frequently occurs in patients who have been diagnosed with multiple sclerosis (MS). Bladder dysfunction (BD) can occur due to the impairment of nerve impulses in the central nervous system regions involved for regulating bladder function and managing the contractions of the urinary sphincters, which is caused by the lesions associated with multiple sclerosis (MS). Urinary retention can cause various symptoms, including insufficient bladder emptying, urinary incontinence, frequent urinary tract infections, urosepsis resulting in the development of kidney abscesses due to localised kidney infection, and reduced kidney function. Optimal bladder function is essential for individuals with MS, as it plays a critical role in preserving kidney health, preventing urinary tract infections and incontinence, reducing the frequency of MS episodes, and improving their overall well-being. A 31-year-old woman was referred to our urology office with a chronic urinary tract infection caused by a neurogenic bladder with a significant volume of residual urine. A kidney abscess formation was identified as a complication. Li-ESWT, which stands for low-intensity extracorporeal shockwave therapy, was used as a part of a multimodal strategy to treat the urinary bladder. This treatment was delivered off-label. The therapy was given on a weekly basis for a period of 6 weeks. The procedure included administering 2500 shocks at a rate of four pulses per second, with an energy flux density (EFD) of 0.25 millijoules per square millimetre. The EFD (Energy Flux Density) used in our study exceeded 0.32 mJmm2,4, the fR (frequency rate) was set at 8 Hz (pulses per second), the treatment sessions consisted of 12 cycles of Li-ESWT (Low-Intensity Extracorporeal Shockwave Therapy), and a total of 3000 shocks were administered. At the intervals of one week, three months, six months, nine months, and twelve months following the administration of Li-ESWT and tadalafil 2.5 mg, the post-void residual (PVR) volume was consistently below 50 ml. The Li-ESWT treatment effectively reduced the post-void residual urine volume.Low-intensity extracorporeal shockwave therapy (Li-ESWT) can safely and efficiently decrease the amount of urine left in the bladder after voiding in individuals with neurogenic bladder caused by multiple sclerosis (MS). We have effectively demonstrated that Li-ESWT is a feasible and safe treatment for chronic urine retention, resulting in a decrease of post-void residual (PVR) volume from 200 ml to 50 ml. In the future, Li-ESWT has the potential to be advanced as a more efficacious alternative therapy for individuals experiencing chronic urinary retention. Further investigation is necessary to confirm the effectiveness of ESWT in addressing the neurogenic bladder.

Impact of low-intensity extracorporeal shockwave therapy on vascular parameters and sexual function in patients with arteriogenic erectile dysfunction.

Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy (Li-ESWT). However, the clinical significance of these findings remains unclear, and definitive selection criteria for Li-ESWT based on preexisting comorbidities have yet to be established. This was an observational study of 113 patients with ED, evaluated between January 2019 and December 2021 in Andrology Unit at the Department of Urology and Renal Transplantation, University of Foggia (Foggia, Italy). Penile dynamic Doppler was performed to evaluate vascular parameters and 5-item version of the International Index of Erectile Dysfunction (IIEF-5) questionnaire was administered to assess the severity of ED. This was repeated 1 month after treatment. Patients with a peak systolic velocity (PSV) <30 cm s -1 were considered eligible for Li-ESWT. Our protocol consisted of 8 weekly sessions with 1500 strokes distributed in 5 different locations along the penis. After treatment, a significant mean (±standard deviation [s.d.]) PSV increase of 5.0 (±3.4) cm s -1 was recorded and 52/113 (46.0%) patients reached a PSV >30 cm s -1 at posttherapeutic penile dynamic Doppler. A clinically significant IIEF-5 score improvement was observed in 7 patients, 21 patients, and 2 patients with mild-to-moderate, moderate, and severe pretreatment ED, respectively. No different outcomes were assessed based on smoking habits, previous pelvic surgery, or use of oral phosphodiesterase-5 inhibitor (PDE5i). On the other side, only 1 (6.7%) in 15 patients with diabetes mellitus showed an IIEF-5 score improvement after Li-ESWT. Shockwave treatment determined a significant increase in PSV and correlated IIEF-5 improvement in ED patients. This advantage seemed particularly evident for moderate ED and was not affected by smoking habits, previous pelvic surgery, and use of PDE5i. Conversely, diabetic patients did not benefit from the treatment.

(281) Low-Intensity Shockwave Therapy Combined with Tadalafil 5mg Daily has Better Efficacy for Mild and Moderate Erectile Dysfunction: The Preliminary Results of a Multicenter Clinical Study in China

Abstract Introduction Most clinical studies have demonstrated that low-intensity extracorporeal shockwave therapy (Li-ESWT) can improved erectile function in patients with erectile dysfunction (ED). The EAU guideline recommended to use Li-ESWT for mild vasculogenic ED patients. However, the therapeutic advantages of Li-ESWT combined with phosphodiesterase type 5 inhibitors (PDE5i) have not been explored clearly in clinical practice for mild and moderate ED patients. Objective To compare the therapeutic effects of Li-ESWT and Li-ESWT combined with PDE5i in mild and moderate ED patients with 8≤IIEF-5≤16 from a multicenter clinical study in China. Methods Patients with ED which IIEF-5 score is less than 22 and aged 18–60 years old were enrolled from three clinical centers from Jun. 2019 to Mar. 2023. The demographic data, International Index of Erectile Function-5 (IIEF-5), erectile hardness score (EHS) and self-reported symptom questions were collected. Patients were treated by a linear low-energy shock waves generator (Renova). Low-intensity shock wave (energy density of 0.09mJ/mm2) treatments were applied (once a week, 4 weeks in total, 5000 shocks each time). Patients in Li-ESWT combined with PDE5i group took 5mg of tadalafil once a day for one continuous month during ESWT. Comparative analyses of pre- and post-treatment and intergroup were used for statistics. Results In total, 42 ED cases (37.43±11.86 years) in Li-ESWT group and 116 cases (37.41±10.14 years) in combined group were enrolled for analysis. The IIEF-5 score and EHS in both groups were significantly improved after 1 month treatment (p&amp;lt;0.01). Compared with Li-ESWT group, patients in combined group significantly had higher self-reported efficiency (61.2% vs. 47.6%, p=0.013), IIEF-5 scores (15.34±7.15 vs. 13.96±7.71, p=0.039) and EHS (2.85±0.82 vs. 2.69±0.89, p=0.050). In the mild and moderate ED (with 8≤IIEF-5≤16) sub-group, 30 ED cases (36.81±10.99 years) in Li-ESWT group and 96 cases (36.80±10.69 years) in combined group were enrolled for analysis. The combined regimen showed better therapeutic advantages, including effective parameters IIEF-5(14.50±6.74 vs. 12.87±8.54, p=0.040), EHS (2.85±0.75 vs. 2.81±0.67, p=0.046) and self-reported efficiency (64.2% vs. 54.1%, p=0.001). Conclusions Li-ESWT can effectively improve erectile function in this multicenter clinical study in China, and the combination of Li-ESWT with daily use PDE5i had a better therapeutic effect on Chinese ED patients, especially on mild and moderate ED. Long-term follow-up with large sample study need to be developed for exploring the optimal therapeutic regimen. Disclosure No.

(138) Efficacy and Patient Satisfaction of Low-Intensity Shockwave Treatment for Erectile Dysfunction in a Retrospective Real-World Study in Japan

Abstract Introduction In Japan, the treatment options for erectile dysfunction (ED) are very restricted, if phosphodiesterase type 5 inhibitors (PDE5Is) are not effective. In this situation, low-intensity extracorporeal shockwave therapy (LiESWT) has gained increased attention as a new option for ED treatment in Japan. Objective To clarify the efficacy of low-intensity extracorporeal shockwave therapy for patients with erectile dysfunction, compare the efficacy between two types of lithotripters (ED1000 [focused type] and Renova [linear type]), and detect factors indicative of therapeutic gain with the treatment. Methods This retrospective study included 76 patients (52.8 +/- 11.7 years) treated by ED1000 (12 times over 9 weeks) and 484 patients (52.5 +/- 11.6 years) treated by Renova (4 times over 4 weeks). Age, sexual symptoms scores, and blood examinations were assessed. Efficacy was judged by improvement of the scores and patient satisfaction and compared between patients at 1 month after treatment with the lithotripters. Independent factors influencing efficacy by Renova were also assessed. Results Sexual symptom scores were improved significantly by both lithotripters, although the changes in the scores did not differ significantly between them. Efficacy rate as judged by patient satisfaction was 65.8% with the ED1000 and 71.1% with Renova, also without significant difference. Among several factors including age, sexual symptoms scores, endocrinological factors, metabolic factors, and the rate of phosphodiesterase type 5 inhibitor use, only age was found to be an independent factor influencing the efficacy of Renova. Conclusions We clearly showed the high efficacy of both lithotripters. Although the efficacy rate did not differ between them, we speculated that the fewer treatment sessions needed with the Renova versus the ED1000 would be a great advantage for patients. We also suggest that Renova should be recommended for patients younger than 70 years of age. Disclosure No.

(313) Low-Intensity Extracorporeal Shockwave Therapy May Result in Improvements in Flaccid Cavernosal Artery Peak Systolic Velocity

Abstract Introduction Low-intensity extracorporeal shockwave therapy (LiESWT) is thought to treat erectile dysfunction (ED) by stimulating neovascularization and nerve regeneration. Studies suggest subjective improvements following treatment, but objective measures are sparse. Objective We aimed to objectively assess the efficacy of LiESWT in the treatment of ED using penile Doppler in men with ED following LiESWT therapy. We hypothesized that LiESWT results in demonstrable increases in penile blood flow. Methods Patients were prospectively enrolled in a clinical trial examining objective and subjective changes in erectile function following LiESWT. Patients underwent baseline examination with penile Duplex ultrasound in both the flaccid and rigid states following intracavernosal injection of alprostadil. Patients received 12 bi-weekly LiESWT treatments of 0.2mJ/mm2 at 5Hz, 1500 shocks delivered per treatment, with follow up Duplex at 1-2 weeks, 4-6 weeks, 3 months and 6 months post-treatment. Highest peak systolic velocity (PSV) and lowest end diastolic velocity (EDV) were reported. Results Twenty-five patients completed all five study visits. The mean highest PSV in the flaccid state prior to treatment was 7.86 cm/s (± 1.47), which significantly increased to 11.31 cm/s (± 1.81, p &amp;lt; 0.05) immediately following completion of treatments. This increase was sustained at 4-6 weeks with a mean PSV of 12.74 cm/s (± 1.80, p &amp;lt; 0.05), followed by 10.74 cm/s (± 1.43, p &amp;lt; 0.05) at 3 months, and 9.87 cm/s (± 1.14, p=0.11) at 6 months (Figure 1). No significant improvements were noted in flaccid lowest EDV or rigid peak PSV/lowest EDV. Conclusions Our results suggest that LiESWT may improve baseline penile vascularity. Overall, the clinical significance of the noted improvement in flaccid PSV after LiESWT remains to be determined and more work needs to be done to define the mechanism of action of LiESWT at a tissue level in human subjects. Disclosure No.

(231) Low-Intensity Extracorporeal Shockwave Therapy Twice Per Week for Six Weeks May Result in Transient Subjective Improvements in Erectile Function

Abstract Introduction Low-intensity extracorporeal shockwave therapy (LiESWT) has been reported to result in subjective improvements in erectile function, but the ideal patient population and treatment protocol have not yet been established. Objective We aimed to assess improvements in International Index of Erectile Function – Erectile Function domain (IIEF-EF) scores following treatment with LiESWT of 1500 shocks of 0.2mJ/mm2 per treatment, twice a week for six weeks. We hypothesized that LiESWT results in subjective improvements of erectile function. Methods Patients were prospectively enrolled in a clinical trial examining changes in erectile function following LiESWT. The study was powered to detect a change in IIEF-EF scores of 5 points. Patients received 12 bi-weekly LiESWT treatments of 0.2mJ/mm2 at 5Hz, 1500 shocks delivered per treatment using the Storz Duolith T-Top Ultra shockwave device. Patients completed IIEF-EF, Sexual Encounter Profile (SEP) questions two and three, Global Assessment Questions (GAQ), and Erection Hardness Score (EHS) questionnaires prior to initiation of treatments and following completion of treatments at 1-2 weeks, 4-6 weeks, 3 months and 6 months post-treatment. Changes in questionnaire responses were compared to baseline responses. Data were analyzed using single variant one-tailed T-tests and one-tailed Fisher’s exact test. Values are reported as means ± standard error. Results Twenty-five patients completed all five study visits. Mean pre-treatment IIEF-EF score was 14.24 ± 1.21. Mean IIEF-EF scores increased to 15.80 ± 1.46 1-2 weeks following treatment (Study Time #2), 16.12 ± 1.46 4-6 weeks following treatment (Study Time #3), 18.12 ± 1.57 3 months following treatment (Study Time #4), and 16.36 ± 1.86 6 months following treatment (Study Time #5), though results only reached significance at Study Time #4 (p=0.016) and results were not sustained. Changes in IIEF-EF scores following treatment were evaluated by baseline ED severity (normal IIEF-EF 26-30, N=1; mild IIEF-EF 22-25, N=2; mild-moderate IIEF-EF 17-21, N=7; moderate IIEF-EF 11-16, N=10; severe IIEF-EF 6-10, N=5. Patients with IIEF-EF scores 11-21 reported significant improvements in IIEF-EF scores at all time points (Figure 1). Mean pre-treatment EHS score was 2.1±0.14. There was no significant improvement in EHS score following treatment at any time point, and no differences when analyzed based on pre-treatment ED severity. Similarly, no changes in SEP or GAQ positive response rates were noted following treatment. Conclusions Our results suggest that LiESWT using 1500 shocks per treatment with energy of 0.2mJ/mm2 twice per week for 6 weeks may transiently improve subjective erectile function as measured using IIEF-EF questionnaires, particularly for patients with mild-moderate to moderately severe ED, consistent with other studies. However, improvements may not be sustained 6 months following treatment. Disclosure No.

(069) Markers of Neovascularization and Neurogenesis May Change After Low-Intensity Extracorporeal Shockwave Therapy for Erectile Dysfunction

Abstract Introduction Low-intensity extracorporeal shockwave therapy (LiESWT) is thought to treat erectile dysfunction (ED) but the mechanism remains elusive. It is believed that LiESWT may work by stimulating neovascularization and nerve regeneration as demonstrated in animal models by histologically increased angiogenesis-related growth factors and neuronal factors including vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS) and brain derived-neurotropic factor (BDNF). Given its prolific use, a thorough understanding of the mechanism of action of this therapy at a cellular level is critical prior to recommendation of this therapy on a larger scale. Objective Objective data post LiESWT is sparse. In this study, we aimed to determine whether markers for neovascularization and nerve regeneration can be detected in the serum of penile tissue in men following LiESWT treatment. We hypothesized that LiESWT results in appreciable increases in vascular and neuronal factors post therapy. Methods Patients were prospectively enrolled in a clinical trial of LiESWT for ED. Patients received 12 bi-weekly LiESWT treatments of 0.2mJ/mm2 at 5Hz, 1500 shocks delivered per treatment, with follow up at 1-2 weeks, 4-6 weeks, 3 months and 6 months post-treatment. Cavernosal penile blood samples were obtained prior to treatment and at each visit post-treatment. The concentrations of eNOS, nNOS, VEGF, and BDNF in penile plasma samples were measured using Enzyme-Linked Immunosorbent Assay (ELISA) with specific commercial kits, following the protocols provided by the manufacturer. Results Twenty-five patients completed all five study visits. Mean patient age was 63. Mean baseline IIEF-EF score prior to treatment was 14.24 (±1.21). At the time of data analysis, plasma samples from 9 men were analyzed for BDNF, eNOS, and nNOS levels using the ELISA assay, and samples from all 25 men were analyzed for VEGF. BDNF levels demonstrated a sustained decrease after the first treatment (P = 0.0001, Figure 1A). Levels of eNOS were noted to trend upward, but no significant changes in eNOS, nNOS or VEGF levels were noted. Conclusions To our knowledge, this is the first study in human tissues to attempt to quantify objective measures of neurogenesis and neovascularization in penile tissue following LiESWT for ED. Though our N is small, our results suggest that LiESWT may decrease BDNF levels after initial LiESWT treatment while VEGF, eNOS and nNOS levels remain unchanged. The clinical significance of these findings is currently unknown, as our findings are not consistent with histological studies in animals which demonstrate upregulation of these markers in penile tissues. However, we believe this represents a promising first step in attempting to understand the effect of LiESWT at a tissue level in men undergoing LiESWT. Disclosure No.