BACKGROUND: Recently we reported results of phase 1 pilot clinical trial of 2 consecutive intracavernous (IC) injection of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) for the first time in the treatment of diabetic patients with erectile dysfunction (DM-ED). In phase 2 of this study our aim is to evaluate long term safety and efficacy of IC injections of BM-MSC on additional eight patients with DM-ED.
RESULTS: Each patient received 2 consecutive IC injections of BM-MSC and evaluated at 1, 3, 6, 12, and 24-month time points. Primary outcome was the tolerability and safety of stem cells therapy (SCT), while the secondary outcome was improvement of erectile function (EF) as assessed using the International Index of Erectile Function-5 (IIEF-5), Erection Hardness Score (EHS) questionnaires, and Color Duplex Doppler Ultrasound (CDDU). IC injections of BM-MSCs was safe and well-tolerated. Minor local and short-term adverse events related to the bone marrow aspiration and IC injections were observed and treated conservatively. There were significant improvement in mean IIEF-5, EHS, all over the follow-up time points in comparison to the baseline. At 24-month follow up there were significant decline in the mean IIEF-5, and EHS compared to the baseline. The mean basal and 20-min peak systolic velocity was significantly higher at 3-month after the IC injections compared to baseline.
CONCLUSIONS: This phase 2 clinical trial confirmed that IC injections of BM-MSC are safe and improve EF. The decline in EF over time suggests a need for assessing repeated injections.
BACKGROUND: NCT02945462.
RéSUMé: CONTEXTE: Récemment, nous avons rapporté les résultats d’un essai clinique pilote de phase 1, de 2 injections intracaverneuses (IC) consécutives de cellules souches mésenchymateuses autologues dérivées de la moelle osseuse (BM-MSC), pour la première fois dans le traitement de patients diabétiques atteints de dysfonction érectile (DM-ED). Dans la phase 2 de cette étude, notre objectif est d’évaluer l’innocuité et l’efficacité à long terme des injections IC de BM-MSC sur huit autres patients atteints de dysfonction érectile. RéSULTATS: Chaque patient a reçu 2 injections IC consécutives de BM-MSC, et a été évalué à des intervalles de temps de 1, 3, 6, 12 et 24 mois. Le critère de jugement principal était la tolérance et l’innocuité de la thérapie par cellules souches, tandis que le critère de jugement secondaire était l’amélioration de la fonction érectile (FE) évaluée à l’aide de l’indice international de la fonction érectile-5 (IIEF-5), de questionnaires sur le score de dureté de l’érection (EHS) et de l’échographie Doppler duplex couleur. Les injections IC de BM-MSC se sont avérées sûres et ont été bien tolérées. Des effets indésirables locaux et à court terme mineurs, liés à l’aspiration de la moelle osseuse et aux injections d’IC, ont été observés et traités de manière conservatrice. Il y a eu une amélioration significative des moyennes de l’IIEF-5 moyen, de l’EHS à tous les points de suivi par rapport à la l’état basal. A 24 mois de suivi, il y a eu une baisse significative de l’IIEF-5 moyen et de l’EHS par rapport à l’état basal. La moyenne se base et celle du pic maximal de la  vitesse systolique à 20 minutes étaient significativement plus élevées 3 mois après les injections de CI par rapport à l’état de base. CONCLUSIONS: Cet essai clinique de phase 2 a confirmé que les injections de BM-MSC par injections intracaverneuses sont sûres et améliorent la fonction érectile. La baisse de cette dernière au fil du temps suggère une nécessité d’évaluation des injections répétées.

UNASSIGNED: Nitric oxide is the most important mediator of penile erection after the onset of sexual excitement. It activates cyclic guanosine monophosphate (cGMP), increasing penile blood flow. Most pharmaceutical medications prevent enzyme phosphodiesterase type 5 (PDE-5) from breaking down cGMP, thus keeping its level high. However, due to the adverse effects of pharmacological therapies, herbal drugs that improve sexual function have gained attention recently. This study aimed to investigate the combined effects of ginseng, Tribulus terrestris, and L-arginine amino acid on the sexual performance of individuals with erectile dysfunction (ED) using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire.
UNASSIGNED: Over three months, 98 men with erectile dysfunction were randomly assigned to receive either 500 mg of herbal supplements or placebo pills. Each herbal tablet contained 100 mg of protodioscin, 35 mg of ginsenosides, and 250 mg of L-arginine.
UNASSIGNED: The results showed that the changes in the average scores of ILEF-5 within each group before and after the intervention indicated that all parameters related to the improvement of sexual function in patients with erectile dysfunction improved in the herbal treatment group (p < 0.001). The herbal group significantly improved IIEF-5 scores in non-diabetics (p < 0.05). However, there was no significant difference in the changes of IIEF-5 scores between the two intervention and control groups in diabetic patients.
UNASSIGNED: In conclusion, ginseng, Tribulus terrestris, and L-arginine have properties that increase energy and strengthen sexual function, making them suitable for patients with sexual disorders.

BACKGROUND: Cardiovascular disease induces erectile dysfunction modulated by endothelial nitric oxide synthase enzyme and an impaired ejection fraction that restricts penis vascular congestion. However, the mechanisms regulating endothelial dysfunction are not understood.
OBJECTIVE: Exploring the functional impact of endothelial nitric oxide synthase genetic polymorphisms on erectile dysfunction and drug therapy optimization in high-risk cardiovascular disease patients.
METHODS: Patients with erectile dysfunction symptoms and candidates for andrology therapy were included (n = 112). Clinical data and endothelial nitric oxide synthase rs1799983 (G894T) and rs2070744 (T-786C), genotyped by fluorescence polarization assays, were registered. The 27-bp variable number of the tandem repeat polymorphism in intron 4 (intron4b/a) was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Association analyses were run with the R-3.2.0 software.
RESULTS: A significant association between endothelial nitric oxide synthase 786-TT (p = 0.005) and the aa/ac of intron 4 variable number of the tandem repeat (p = 0.02) with higher erectile dysfunction susceptibility was observed in cardiovascular disease patients (60 ± 9 years, 66% severe erectile dysfunction, 56% ejection fraction). After 3-months of phosphodiesterase type 5 inhibitors, erectile dysfunction (International Index of Erectile Function, 50 ± 16 scores, the International Index of Erectile Function-Erectile Function 21 ± 10 scores, p < 0.001) and sexual quality of life (modified Sexual Life Quality Questionnaire 55 ± 23 scores, p < 0.001) had significantly improved. The cardiovascular ejection fraction was influenced positively with better sexual quality of life (0.1941), and also in the endothelial nitric oxide synthase G894-T allele (p = 0.076) carriers, which could merit future analyses. Erectile dysfunction was present as the primary clinical manifestation in 62% of cases, with cardiovascular disease occurring concurrently. Only former smokers and obese subjects debuted prior to cardiovascular disease than to erectile dysfunction.
CONCLUSIONS: Our study provides comprehensive insights into the functional interaction linking endothelial nitric oxide synthase gene polymorphisms, erectile function, and ejection fraction in high-risk cardiovascular disease patients. Future therapeutic strategies could target endothelial nitric oxide synthase activity by including lifestyle changes and epigenetic modulations.

The existing research on the association between apolipoproteins (Apos) and erectile dysfunction (ED) primarily relies on observational studies and does not distinguish between organic and psychogenic causes when diagnosing ED. It is difficult to believe that Apos play a role in psychogenic ED. To address these issues, our study explored the causal relationship between lipoproteins and ED using Mendelian randomization (MR) analysis and differentiate between organic and psychogenic ED through the use of nocturnal penile tumescence and rigidity (NPTR) monitoring. Multivariate MR analysis revealed significant causal associations between high-density lipoprotein (HDL), Apo A1, and Apo B/A1 with ED (OR and 95% CI were 0.33 (0.14-0.78), 3.58 (1.52-8.43), and 0.30 (0.13-0.66)). we conducted statistical and analytical analyses on the data of 212 patients using multivariate analyses and receiver operating characteristic (ROC) curves. Patients with organic ED had significantly lower levels of HDL, Apo A1 and Apo A1/B, whereas patients with organic ED had considerably higher levels of Apo B and low-density lipoprotein (LDL). The diagnostic value of Apos in predicting the risk of organic ED was evaluated using ROC curves. The results indicated that Apo A1 and Apo A1/B demonstrated good predictive value. HDL, Apo A1, and Apo A1/B have been identified as risk factors for ED in our study. Furthermore, our research highlights the significance of Apo A1 and Apo A1/Apo B in the development of organic ED and suggests their potential use as indicators to assess the risks associated with organic ED.

UNASSIGNED: Serum 25-hydroxyvitamin D level is associated with erectile dysfunction (ED) in observational studies. However, whether there is a causal association between them remains uncertain.
UNASSIGNED: Conduct a two-sample Mendelian randomization (MR) analysis to investigate the causal effect between serum 25-hydroxyvitamin D level and ED risk.
UNASSIGNED: Genome-wide association study (GWAS) data of serum 25-hydroxyvitamin D levels comprising 6,896,093 single nucleotide polymorphisms (SNP) from 496,949 people of European ancestry were regarded as exposure for the MR analysis. Additional GWAS data involving 9,310,196 SNPs of 6,175 European ED cases and 217,630 controls were used as outcome data. The MR-Egger, inverse variance weighted (IVW) method, weighted median, simple mode, and weighted mode were employed to evaluate causal effects, among which IVW was the primary MR analysis method. The stability of the MR analysis results was confirmed by a heterogeneity test, a horizontal pleiotropy test, and the leave-one-out method.
UNASSIGNED: There were 103 SNPs utilized as instrumental variables (p < 5 × 10-8). The results of MR analysis showed no causal effects of serum 25(OH) D concentration on ED risks (IVW; OR = 0.9516, 95% CI = 0.7994 to 1.1328, p = 0.5772). There was no heterogeneity and pleiotropy in the statistical models.
UNASSIGNED: The present MR study did not support a causal association for genetically predicted serum 25-hydroxyvitamin D concentration in the risk of ED in individuals of European descent.

We aimed to establish the prevalence of atypical masturbation in the general population and explore the association between atypical masturbation and male sexual dysfunction in heterosexual males. Atypical masturbation refers to stimulation significantly distinct from that encountered during partnered sexual activity. We posted questionnaires that contained the abridged International Index of Erectile Function (IIEF-6) and the premature ejaculation diagnostic tool on social media in China. We collected 2743 valid questionnaires from December 9, 2020, to April 18, 2021. We found that the prevalence of atypical masturbation in the general population was 10.97%. Men with atypical masturbation had lower IIEF-6 scores and higher rates of erectile dysfunction (ED) than men with typical masturbation. The prevalence of premature ejaculation and estimated intravaginal ejaculatory latency time were not significantly different among men with different patterns of masturbation. Our study demonstrated that atypical masturbation is associated with ED, and a clinician dealing with sexual issues should inquire more fully about masturbation patterns than has been done to date.

UNASSIGNED: Erectile Dysfunction (ED) is a common challenge post Radical Prostatectomy (RALP), affecting men\'s sexual health after undergoing definitive cancer therapy. Despite employing nerve-sparing techniques, ED remains a prevalent issue in this population. Studies indicate that approximately 70%-85% of men experience varying degrees of ED following RALP. The existing treatment landscape for post-RALP-ED presents limitations, and a discernible knowledge gap persists. To address this, our study aims to investigate the efficacy of Shockwave Therapy (SWT) as a potential intervention for managing ED after RALP.
UNASSIGNED: This prospective, randomized, sham-controlled clinical trial aims to recruit 189 eligible patients post-RP and assess the effects of SWT. Comprehensive screening, including medical history, physical examinations, and biochemical evaluations, will be conducted to confirm eligibility. The intervention involves utilizing a device to administer focal shockwaves targeted at cavernosal tissue. Safety measures include continuous monitoring for adverse events and rigorous reporting protocols. The primary endpoint assesses changes in participants\' ability to engage in penetrative intercourse from baseline to study completion, while secondary endpoints encompass various measures of erectile function, including questionnaire-based assessments, ultrasound parameters, and clinical outcomes.
UNASSIGNED: Statistical analysis, encompassing ANOVA for continuous variables and Fisher\'s exact test for categorical ones, will evaluate demographic characteristics, baseline data, and primary as well as secondary outcomes for statistical significance. Detailed analysis of trends, subgroup comparisons, and treatment effects will provide a comprehensive understanding of the impact of SWT on post-RP ED.
UNASSIGNED: This study protocol represents a rigorous investigation into the potential therapeutic role of SWT in managing post-RP ED. The outcomes from this study aim to contribute valuable insights into the efficacy, safety, and potential improvements in erectile function following SWT, providing significant guidance for future interventions aimed at addressing this challenging condition affecting men\'s health and quality of life.

Peyronie\'s disease (PD) affects the penile albuginea, resulting in penile deformity, pain, erectile dysfunction (ED), and an anxious-depressive state. PD diagnosis involves a thorough medical history, penile palpation, documentation of the penile deformation, a dynamic penile echo color Doppler ultrasound (PCDU), and the completion of questionnaires for the evaluation of pain, ED, and psychometric tests. The aim of this study was to evaluate the symptoms of PD and their prevalence in PD patients in the active phase who had access to our andrology clinic. Inclusion criteria: availability of data on patients diagnosed with PD, including detailed medical history, blood tests, penile palpation, photographic documentation of penile deformity, and penile PCDU. Exclusion criteria: PD patients in the stable phase or those without the specified tests and data mentioned above. Our study found a higher prevalence of PD in younger patients (24.2%), a higher coexistence of PD with chronic prostatitis (35.6%), a higher percentage of cases of association between penile deformity and penile curvature (84.4%), a higher prevalence of \"significant anxiety\" (88.4%), a higher presence of plaque calcification (35.6%), and the detection of a longer duration of the first phase of PD (>18 months). The most frequently observed type of penile curvature was dorsal, followed by left lateral, right lateral, and, less commonly, ventral. We observed a significant statistical correlation between patient age and IIEF score, indicating that patients over the age of 40 years are at a higher risk of experiencing ED. We found a strong statistical relationship between VAS score and age. As age increases, the VAS score decreases, suggesting that younger patients reported more penile pain compared to those who were older than 40 years. Furthermore, we found that penile pain has a significant impact on the psychological state of PD patients. We also found that 38.8% of PD patients suffered from severe anxiety. In relation to this, psychotherapy should be integrated into PD treatment to improve the quality of life and treatment adherence.

Background: Erectile dysfunction (ED) most often has vascular etiology and usually is the earliest symptom of vascular dysfunction. The aim of this study was to evaluate vascular dysfunction with the use of the Flow-Mediated Skin Fluorescence (FMSF) technique in men with and without ED. Methods: Included were 39 men (median age 53) with ED and 40 men (median age 41.5) without ED. Medical interview, physical examination, and anthropometrical measurements were performed for all participants. The serum total testosterone, LH, and SHBG determinations were performed in patients with ED, and the Free Testosterone Index (FTI) was calculated. The FMSF technique was used to measure the microcirculatory oscillations at the baseline and to determine the flowmotion (FM) and vasomotion (VM) parameters. The Normoxia Oscillatory Index (NOI) was calculated, which represents the contribution of the endothelial (ENDO) and neurogenic (NEURO) oscillations relative to all oscillations detected at low-frequency intervals (<0.15 Hz): NOI = (ENDO + NEURO)/(ENDO + NEURO + VM). Results: In men with ED were found significantly lower FM and VM parameters, but the NOI was significantly higher in comparison to men without ED. VM and FM correlated significantly positively with erectile function, orgasmic function, and general sexual satisfaction in the whole group and the FTI in the ED group. The thresholds of 53.5 FM (AUC = 0.7) and 8.4 VM (AUC = 0.7) were predictive values for discriminating men with ED. Conclusions: It was shown that the FMSF diagnostic technique may be helpful in the early diagnosis of microcirculation dysfunction due to impaired vasomotion caused by decreased testosterone activity.

BACKGROUND: Metabolic syndrome (MS) has emerged as a new health risk, and its associated metabolic derangements have detrimental effects on the cardiovascular system. In recent years, MS has been reported to affect reproductive health in males. It has been reported to be associated with erectile dysfunction (ED) and has been attributed to be due to endothelial dysfunction. Poor endothelial function in ED usually affects small-sized vasculature, so it can be looked at as a predictor for the endothelial dysfunction of macro vasculature. The aim of the present study was to determine the association of ED in patients with MS and to determine its correlation with endothelial dysfunction.
METHODS: It was a hospital-based case-control study in which 120 male patients with MS and 120 age-matched controls were enroled. Demographic profiles, anthropometry, past illnesses, and medical history of patients were obtained. MS was diagnosed according to the International Diabetes Federation (IDF) criteria and was measured using the flow-mediated dilation (FMD) method with the help of ultrasound used to assess endothelial dysfunction. Diagnosis of ED was based on the International Index of Erectile Function (IIEF) scale.
RESULTS: The study participants had a mean age of 40.91 ± 11.41 years. The majority of cases (57.5%) had ≤6 months of history of MS. The prevalence of ED was 31.7% in cases compared to 5% in controls, thus showing a significant difference between cases and controls. Mean IIEF scores were significantly lower in cases (18.82 ± 5.59) compared to those in controls (23.00 ± 2.57). A moderate positive and significant correlation was observed between FMD and IIEF scores. With an increasing number of MS components, there was a significant increase in the prevalence of ED. Those with ED had significantly lower mean FMD values (5.1 ± 1.1%) compared to those not having ED (10.9 ± 3.3%).
CONCLUSIONS: The findings of the present study showed that there is a significant association between ED and MS. We observed that the increase in components of MS increased the prevalence of ED in MS. Endothelial dysfunction measured by FMD was correlated with ED.