Acupuncture for erectile dysfunction: a randomized controlled trial. / é’ˆåˆºæ²»ç–—å‹ƒèµ·åŠŸèƒ½éšœç¢ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical efficacy of acupuncture in treating erectile dysfunction (ED). METHODS: A total of 64 ED patients were randomly divided into an acupuncture group (32 cases, 2 case dropped out) and a western medication group (32 cases, 2 cases dropped out). In the acupuncture group, acupuncture treatment was applied at Baihui (GV 20), Qihai (CV 6), Guanyuan (CV 4), Zhongji (CV 3), Dahe (KI 12), Qugu (CV 2), Zusanli (ST 36), and etc., two groups of acupoints were used alternately, 30 min each time, once every other day. In the western medication group, 50 mg of sildenafil tablet was took orally 1 h before sexual activity. Both groups were treated for 30 d. The international index of erectile function citrate (IIEF-5) score, self rating anxiety scale (SAS) score, self rating depression scale (SDS) score, TCM syndrome score were observed before and after treatment, and in follow-up of 2 weeks after treatment completion, the serum testosterone (T) level was detected before and after treatment, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment and in follow-up, the IIEF-5 scores were increased compared with those before treatment in the two groups (P<0.01). In follow-up, the IIEF-5 score in the acupuncture group was ascended compared with that in the western medication group (P<0.05). Except for the SDS and TCM syndrome scores in the western medication group of follow-up, the SAS scores, SDS scores, and the TCM syndrome scores were decreased after treatment and in follow-up compared with those before treatment in the two groups (P<0.01, P<0.05); in the acupuncture group, the SAS scores, SDS scores and the TCM syndrome scores after treatment and in follow-up were lower than those in the western medication group (P<0.01). After treatment, the serum T levels were increased compared with those before treatment in the two groups (P<0.01). The total effective rate of the acupuncture group was 83.3% (25/30), and it was 86.7% (26/30) in the western medication group, there was no significant difference in total effective rate between the two groups (P>0.05). CONCLUSIONS: Acupuncture can effectively improve erectile function, anxiety and depression state, and TCM syndrome in ED patients, and has a advantage of posterior effect compared with western medication treatment.

Testicular Cancer Treatments and Sexuality: A Narrative Review.

The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing the patient different treatment approaches according to histology and tumor stage. Currently, physicians usually prioritize oncological outcomes over sexual outcomes and quality of life, considering as a first aim the overall survival of the patients; however, differently from other neoplasms, quality of life is still strongly affected among TC patients, and sexual outcomes are frequently compromised after each TC treatment. Several studies have suggested that each treatment approach may be associated with sexual dysfunctions, including erectile dysfunction, ejaculatory disorders, fertility issues, and hormonal changes. Since testicular cancer patients are more frequently young men, the subject of this work is substantial and should be analyzed in detail to help specialists in the management of this disease. The aim of the current narrative review is to generally describe every treatment for TC, including surgery, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, and to establish which sexual dysfunction may be specifically associated with each therapy.

High-intensity focused ultrasound with visually directed power adjustment for focal treatment of localized prostate cancer: systematic review and meta-analysis.

PURPOSE: To characterize patient outcomes following visually directed high-intensity focused ultrasound (HIFU) for focal treatment of localized prostate cancer. METHODS: We performed a systematic review of cancer-control outcomes and complication rates among men with localized prostate cancer treated with visually directed focal HIFU. Study outcomes were calculated using a random-effects meta-analysis model. RESULTS: A total of 8 observational studies with 1,819 patients (median age 67 years; prostate-specific antigen 7.1 mg/ml; prostate volume 36 ml) followed over a median of 24 months were included. The mean prostate-specific antigen nadir following visually directed focal HIFU was 2.2 ng/ml (95% CI 0.9-3.5 ng/ml), achieved after a median of 6 months post-treatment. A clinically significant positive biopsy was identified in 19.8% (95% CI 12.4-28.3%) of cases. Salvage treatment rates were 16.2% (95% CI 9.7-23.8%) for focal- or whole-gland treatment, and 8.6% (95% CI 6.1-11.5%) for whole-gland treatment. Complication rates were 16.7% (95% CI 9.9-24.6%) for de novo erectile dysfunction, 6.2% (95% CI 0.0-19.0%) for urinary retention, 3.0% (95% CI 2.1-3.9%) for urinary tract infection, 1.9% (95% CI 0.1-5.3%) for urinary incontinence, and 0.1% (95% CI 0.0-1.4%) for bowel injury. CONCLUSION: Limited evidence from eight observational studies demonstrated that visually directed HIFU for focal treatment of localized prostate cancer was associated with a relatively low risk of complications and acceptable cancer control over medium-term follow-up. Comparative, long-term safety and effectiveness results with visually directed focal HIFU are lacking.

Poly-L-lactic acid/gelatin electrospun membrane-loaded bone marrow-derived mesenchymal stem cells attenuate erectile dysfunction caused by cavernous nerve injury.

Radical prostatectomy (RP) can cause neurogenic erectile dysfunction (ED), which negatively affects the quality of life of patients with prostate cancer. Currently, there is a dearth of effective therapeutic strategies. Although stem cell therapy is promising, direct cell transplantation to injured cavernous nerves is constrained by poor cell colonization. In this study, poly-L-lactic acid (PLLA)/gelatin electrospun membranes (PGEM) were fabricated to load bone marrow-derived mesenchymal stem cells (BM-MSCs) as a patch to be placed on injured nerves to alleviate ED. This study aimed to establish a promising and innovative approach to mitigate neurogenic ED post-RP and lay the foundation for modifying surgical procedures. Electrospinning and molecular biotechnology were performed in vitro and in vivo, respectively. It was observed that PGEM enhanced the performance of BM-MSCs and Schwann cells due to their excellent mechanical properties and biocompatibility. The transplanted PGEM and loaded BM-MSCs synergistically improved bilateral cavernous nerve injury-related ED and the corresponding histopathological changes. Nevertheless, transplantation of BM-MSCs alone has been verified to be ineffective. Overall, PGEM can serve as an ideal carrier to supply a more suitable survival environment for BM-MSCs and Schwann cells, thereby promoting the recovery of injured cavernous nerves and erectile function.

Research Advances in Stem Cell Therapy for Erectile Dysfunction.

Erectile dysfunction (ED) is a common clinical condition that mainly affects men aged over 40 years. Various causes contribute to the progression of ED, including pelvic nerve injury, diabetes, metabolic syndrome, age, Peyronie's disease, smoking, and psychological disorders. Current treatments for ED are limited to symptom relief and do not address the root cause. Stem cells, with their powerful ability to proliferate and differentiate, are a promising approach for the treatment of male ED and are gradually gaining widespread attention. Current uses for treating ED have been studied primarily in experimental animals, with most studies observing improvements in erectile quality as well as improvements in erectile tissue. However, research on stem cell therapy for human ED is still limited. This article summarizes the recent literature on basic stem cell research on ED, including cavernous nerve injury, aging, diabetes, and sclerosing penile disease, and describes mechanisms of action and therapeutic effects of various stem cell therapies in experimental animals. Stem cells are also believed to interact with host tissue in a paracrine manner, and improved function can be supported through both implantation and paracrine factors. To date, stem cells have shown some preliminary promising results in animal and human models of ED.

Iron homeostasis alterations and erectile dysfunction: A new issue in erectile disfunction treatment?

To the Editor, Erectile dysfunction (ED) is one of the most prevalent conditions affecting men globally, with significant psychological and social consequences. The prevalence varies across different populations, and it is estimated around 50% in men aged between 40 to 70. The etiology of ED is multifactorial, involving a complex crosstalk between psychological, hormonal, neurogenic, vascular, and structural factors [...].

Fibroblasts enable penile erection.

Perivascular fibroblasts may underlie erectile dysfunction.

The pathogenic role of the immune system in erectile dysfunction and Peyronie's disease: focusing on immunopathophysiology and potential therapeutic strategies.

INTRODUCTION: Erectile dysfunction (ED) represents the major cause of male sexual dysfunction, which is often associated with obesity, diabetes mellitus, atherosclerotic cardiovascular disease, and cigarette smoking. Peyronie's disease is a chronic disorder associated with irreversible fibrotic damage of the tunica albuginea leading to ED, painful erection, coital disturbance, and physical and social complaints. Both conditions are characterized by chronic inflammation, oxidative stress, and significant changes in intracavernous hydrodynamics. In this scenario, oxidized lipoproteins, M1-polarized macrophages, proinflammatory cytokines (such as the tumor necrosis factor α), endothelial nitric oxide synthase, penile smooth muscle cells, and toll-like receptors represent the main triggers of the inflammatory process in ED. Phosphodiesterase-5 inhibitors are the most common treatment for ED. This treatment is used intermittently, as it is conceived as a symptomatic and not curative therapy. Moreover, not all patients respond to phosphodiesterase-5 inhibitors (35%-85%), particularly those with dysmetabolic phenotypes. Additional or alternative treatments are therefore desirable, mostly in refractory cases. OBJECTIVES: In this review, we describe the immune-mediated pathogenesis of ED and Peyronie's disease (PD). In our literature search we placed particular emphasis on potentially practical therapeutic approaches, including natural products (such as polyphenols), due to their anti-inflammatory and antioxidant activities, stem cell therapy, and platelet-derived preparations. METHODS: We searched PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library, Google Scholar, and institutional websites. Original studies, narrative reviews, systematic reviews, and meta-analyses written in English were searched, screened, and selected. RESULTS: In animal models of ED and PD, therapeutic approaches, including anti-inflammatory and antioxidant agents, stem cell therapy, and platelet-derived preparations, have provided positive results, including improved penile function, reduced inflammation and oxidative stress, and promotion of tissue repair. However, clinical evidence of improvement in human patients is still insufficient. CONCLUSION: Promising results for treating ED and PD have been shown in preclinical and pilot clinical studies, but specific clinical trials are needed to validate the efficacy of these therapeutic approaches in men with ED.

Long-term outcomes of extracorporeal shock wave therapy for acute Peyronie's disease: a 10-year retrospective analysis.

The aim of this paper was to describe the long-term outcomes of extracorporeal shock wave therapy (ESWT) in patients with acute Peyronie'disease (PD). An observational retrospective study was conducted in men with acute PD who underwent ESWT between 2009-2013 at a single institution. ESWT protocol consisted of 1 session (3000 shock waves, 0.10-0.25 mJ/mm^2, 4-6 Hz) per week for 4 weeks. Penile pain was chosen as the primary outcome. Penile curvature angle, erectile function, and satisfaction with ESWT were selected as secondary long-term outcomes. A total of 194 patients were included. The mean follow-up duration after ESWT was 125.6 months. Mean penile curvature worsened significantly at 3 months (18.3 vs. 21.5 degrees; p = 0.023) and 12 months (21.5 vs. 28.6 degrees; p = 0.001) and stabilized over the long-term (28.6 vs. 28.8 degrees; p = 0.335). Mean penile pain improved significantly at 3 months (6.5 vs. 3.1 points; p < 0.001) and 12 months (3.1 vs. 1.0 points; p = 0.001), remaining stable over time (1.0 vs. 1.0 points; p = 0.074). The mean five-item version of the International Index of Erectile Function (IIEF-5) increased significantly at 3 months (14.5 vs. 17.9 points; p = 0.001), remaining stable at 12 months (17.9 vs. 18.5 points; p = 0.082), and deteriorating in the long-term (18.5 vs. 15.8 points; p = 0.003). A high satisfaction rate with ESWT was recorded at 3 months (92.3%), remaining similar at 12 months (91.2%) and over the long-term (90.2%). No new acute phase and low rate of PD surgery (4.1%) were recorded in the long-term analysis. In patients with acute PD, ESWT seems to be associated with early and persistent relief of penile pain, transient improvement in erectile function, no significant effect on penile curvature, and a high rate of patient satisfaction constant over time.

d-Galactose induces the senescence and phenotype switch of corpus cavernosum smooth muscle cells.

Studies regarding age-related erectile dysfunction (ED) based on naturally aging models are limited by their high costs, especially for the acquisition of primary cells from the corpus cavernosum. Herein, d-galactose ( d-gal) was employed to accelerate cell senescence, and the underlying mechanism was explored. As predominant functional cells involved in the erectile response, corpus cavernosum smooth muscle cells (CCSMCs) were isolated from 2-month-old rats. Following this, d-gal was introduced to induce cell senescence, which was verified via ß-galactosidase staining. The effects of d-gal on CCSMCs were evaluated by terminal deoxynucleoitidyl transferase dUTP nick-end labeling (TUNEL), immunofluorescence staining, flow cytometry, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, RNA interference (RNAi) was carried out for rescue experiments. Subsequently, the influence of senescence on the corpus cavernosum was determined via scanning electron microscopy, qRT-PCR, immunohistochemistry, TUNEL, and Masson stainings. The results revealed that the accelerated senescence of CCSMCs was promoted by d-gal. Simultaneously, smooth muscle alpha-actin (alpha-SMA) expression was inhibited, while that of osteopontin (OPN) and Krüppel-like factor 4 (KLF4), as well as fibrotic and apoptotic levels, were elevated. After knocking down KLF4 expression in d-gal-induced CCSMCs by RNAi, the expression level of cellular alpha-SMA increased. Contrastingly, the OPN expression, apoptotic and fibrotic levels declined. In addition, cellular senescence acquired partial remission. Accordingly, in the aged corpus cavernosum, the fibrotic and apoptotic rates were increased, followed by downregulation in the expression of alpha-SMA and the concurrent upregulation in the expression of OPN and KLF4. Overall, our results signaled that d-gal-induced accelerated senescence of CCSMCs could trigger fibrosis, apoptosis and phenotypic switch to the synthetic state, potentially attributed to the upregulation of KLF4 expression, which may be a multipotential therapeutic target of age-related ED.

Serum Testosterone Concentration Influences the Response to Extracorporeal Shock Wave Treatment in Men With Peyronie's Disease.

OBJECTIVE: To assess the relationship between baseline total serum testosterone (T) and clinical outcomes in men affected by Peyronie's disease (PD) stable stage and treated by extra corporeal shockwave therapy (ESWT). METHODS: In this study, 168 patients affected by PD in stable stage (≥12 months) and treated with ESWT, were divided into 2 groups. Group 1 (G1) counted 71 patients with low T levels (≤ 300 ng/dL); group 2 (G2) consisted of 97 patients with normal T that received ESWT with the same protocol of G1 for 6 weeks. There were assessed at baseline and follow-up: Erectile dysfunction (ED), presence and severity of painful erections, penile plaque size, and penile curvature degree. The results were evaluated at baseline and 3, 6, 12, months after the treatment. RESULTS: Not statistically significant differences emerged between the 2 groups at baseline, except for higher presence of patients with ED in G1 (90%) vs G2 (52%). Three months after the treatment in G2 pain was resolved completely in 80.4% of the patients, compared with G1 (54.9%). G2 had a reduction of curvature degree after the 3-month treatment (P <.001). Mean plaque size decreased in both groups without statistically differences with baseline values. Mean ± SD International Index of Erectile Function-5 score progressively improved significantly in the eugonadal men. CONCLUSION: This study demonstrated greater efficacy for the treatment of PD in men with normal T concentrations compared with men with low T concentrations. The results obtained from this study suggest that may be valuable in considering T therapy in men with PD prior to ESWT.

Dual Strategy with Adipose-Derived Stem Cells and l-arginine Recovered Cavernosal Functions in a Rat Model of Radical Prostatectomy.

As standard therapy for prostate cancer, radical prostatectomy causes cavernous nerve (CN) injury and increases fibrosis and hypoxia-induced penile structural alterations. This study aimed to determine the potential beneficial effects of adipose-derived stem cells (ADSCs) and l-arginine alone or in combination on the penile erection in a rat model of erectile dysfunction caused by bilateral cavernous nerve transection (CNT). Male rats (n = 35) were randomized into five groups: Sham-operated; CNT (4-weeks); CNT plus ADSCs (1 × 106 cells by intracavernosal injection); CNT plus l-arginine (4 weeks, 10 mg/kg/day, oral); and ADSCs combined with l-arginine in CNT. In vivo erectile responses and in vitro relaxant responses were measured. Western blot and immunohistochemistry analyses were used to determine the expression and localization of endothelial nitric oxide synthase, neuronal nitric oxide synthase, transforming growth factor-beta 1, hypoxia-inducible factor-1 alpha (HIF-1α), and apoptosis markers (Bax and Bcl-2). The ratio of smooth muscle to collagen and nerve regeneration were calculated using Masson's trichrome and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. The combined treatment restored diminished erectile responses, endothelium-dependent acetylcholine, and electrical field stimulation-induced relaxation of the corpus cavernosum in rats with CNT, whereas either monotherapy produced only partial improvements. All treatment regimens restored increases in the protein expression of HIF-1 and Bax in rats with CNT. The decrease in smooth muscle mass and NADPH-diaphorase-positive nerve fibers was partially ameliorated by monotherapy, whereas combined therapy led to recovery. These findings indicate that combined treatment with ADSCs and l-arginine may restore erectile function in rats with CNT by inhibiting hypoxia-induced neurotoxicity and preserving endothelium function and smooth muscle content.

Men with erectile dysfunction (ED) should be screened for cardiovascular risk factors - Cost-benefit considerations in Swiss men.

Background: Current evidence indicates that erectile dysfunction (ED) is an independent risk factor for future cardiovascular events. This study aimed to estimate the cost-effectiveness of screening and subsequent preventive treatment for cardiovascular risk factors among men newly diagnosed with ED from the Swiss healthcare system perspective. Methods: Based on known data on ED and cardiovascular disease (CVD) prevalence and incidence costs and effects of a screening intervention for cardiovascular risk including corresponding cardiovascular prevention in men with ED were calculated for the Swiss population over a period of 10 years. Results: Screening and cardiovascular prevention over a period of 10 years in Swiss men with ED of all seriousness degrees, moderate and severe ED only, or severe ED only can probably avoid 41,564, 35,627, or 21,206 acute CVD events, respectively. Number needed to screen (NNS) to prevent one acute CVD event is 30, 23, and 10, respectively. Costs for the screening intervention are expected to be covered at the seventh, the fifth, and the first year, respectively. Conclusion: Screening and intervention for cardiovascular risk factors in men suffering from ED is a cost-effective tool not only to strengthen prevention and early detection of cardiovascular diseases but also to avoid future cardiovascular events.

Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury.

OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

MicroRNA-148a-3p in pericyte-derived extracellular vesicles improves erectile function in diabetic mice by promoting cavernous neurovascular regeneration.

BACKGROUND: To investigate the regulatory role of microRNA (miR)-148a-3p in mouse corpus cavernous pericyte (MCPs)-derived extracellular vesicles (EVs) in the treatment of diabetes-induced erectile dysfunction (ED). METHODS: Mouse corpus cavernous tissue was used for MCP primary culture and EV isolation. Small-RNA sequencing analysis was performed to assess the type and content of miRs in MCPs-EVs. Four groups of mice were used: control nondiabetic mice and streptozotocin-induced diabetic mice receiving two intracavernous injections (days - 3 and 0) of phosphate buffered saline, MCPs-EVs transfected with reagent control, or MCPs-EVs transfected with a miR-148a-3p inhibitor. miR-148a-3p function in MCPs-EVs was evaluated by tube-formation assay, migration assay, TUNEL assay, intracavernous pressure, immunofluorescence staining, and Western blotting. RESULTS: We extracted EVs from MCPs, and small-RNA sequencing analysis showed miR-148a-3p enrichment in MCPs-EVs. Exogenous MCPs-EV administration effectively promoted mouse cavernous endothelial cell (MCECs) tube formation, migration, and proliferation, and reduced MCECs apoptosis under high-glucose conditions. These effects were significantly attenuated in miR-148a-3p-depleted MCPs-EVs, which were extracted after inhibiting miR-148a-3p expression in MCPs. Repetitive intracavernous injections of MCPs-EVs improved erectile function by inducing cavernous neurovascular regeneration in diabetic mice. Using online bioinformatics databases and luciferase report assays, we predicted that pyruvate dehydrogenase kinase-4 (PDK4) is a potential target gene of miR-148a-3p. CONCLUSIONS: Our findings provide new and reliable evidence that miR-148a-3p in MCPs-EVs significantly enhances cavernous neurovascular regeneration by inhibiting PDK4 expression in diabetic mice.

Heart Failure and Erectile Dysfunction: a Review of the Current Evidence and Clinical Implications.

PURPOSE OF REVIEW: Heart failure (HF) and erectile dysfunction (ED) are two common conditions that affect millions of men worldwide and impair their quality of life. ED is a frequent complication of HF, as well as a possible predictor of cardiovascular events and mortality. ED deserves more attention from clinicians and researchers. RECENT FINDINGS: The pathophysiology of ED in HF involves multiple factors, such as endothelial dysfunction, reduced cardiac output, neurohormonal activation, autonomic imbalance, oxidative stress, inflammation, and drug side effects. The diagnosis of ED in HF patients should be based on validated questionnaires or objective tests, as part of the routine cardiovascular risk assessment. The therapeutic management of ED in HF patients should be individualized and multidisciplinary, considering the patient's preferences, expectations, comorbidities, and potential drug interactions. The first-line pharmacological treatment for ED in HF patients with mild to moderate symptoms (NYHA class I-II) is phosphodiesterase type 5 inhibitors (PDE5Is), which improve both sexual function and cardiopulmonary parameters. PDE5Is are contraindicated in patients who use nitrates or nitric oxide donors for angina relief, and these patients should be advised to avoid sexual activity or to use alternative treatments for ED. Non-pharmacological treatments for ED, such as psychotherapy or couples therapy, should also be considered if there are significant psychosocial factors affecting the patient's sexual function or relationship. This review aims to summarize the most recent evidence regarding the prevalence of ED, the pathophysiology of this condition with an exhaustive analysis of factors involved in ED development in HF patients, a thorough discussion on diagnosis and management of ED in HF patients, providing practical recommendations for clinicians.

Non-invasive alternative for phosphodiesterase inhibitor-refractory erectile dysfunction: Real-life experience with low-intensity extracorporeal shockwave therapy.

This retrospective study assessed the efficacy of low-intensity extracorporeal shockwave therapy (Li-ESWT) in the treatment of erectile dysfunction (ED) in patients unresponsive to phosphodiesterase inhibitors (PDE5is). Between May 2020 and December 2022, we retrospectively analyzed the records of 126 ED patients who underwent Li-ESWT post unsuccessful PDE5is trials, defined as inadequate response following at least 6 consistent trials with correct dosage (preference given to 20 mg tadalafil). Patients with neurogenic disorders were excluded. Patients' ED severity was determined using the IIEF-5 score and further categorized into 2 groups. The Li-ESWT treatment protocol consisted of 12 weeks. Data was analyzed using descriptive statistics and paired t-tests. In the cohort of 126 patients, the mean age was 50.5 ±â€…12.4 years, with a BMI of 29.18 ±â€…3.49. Notably, 74.6% had ED for more than 12 months. Before Li-ESWT, 55.6% used sildenafil and 44.4% used tadalafil. Post 3 months of Li-ESWT, the average IIEF score rose significantly from 10.19 ±â€…7.71 to 14.29 ±â€…0.92 (P < .01). Particularly, Group 2 exhibited a significant improvement in their mean IIEF score from 13.78 ±â€…1.38 pretreatment to 21 ±â€…2.31 post-treatment. However, Group 1 (with higher diabetes prevalence) showed a marginal rise from 5.8 ±â€…1.47 to 6.1 ±â€…3.2 (P = .14). Similarly, the overall EHS score progressed significantly from 1.34 ±â€…0.8 to 2.3 ±â€…1.17 post-treatment. Post-treatment, while Group 1 showed no changes in successful vaginal penetration, Group 2 reported a dramatic increase in successes, from 16 before treatment to 68 after. This study demonstrated the efficacy of Li-ESWT for PDE5is-refractory ED, particularly in patients with moderate to mild ED. However, patients with severe ED and comorbidities did not show significant improvement. Further research with larger sample sizes, control groups, longer follow-up periods, and standardized protocols is required to confirm the effectiveness and limitations of Li-ESWT in ED treatment.