OBJECTIVE: While international guidelines advocate for a multifaceted approach to treating erectile dysfunction (ED) involving physical activities, psychological support, and education, structured programs are infrequent. To address this gap, an app-based therapy was developed, offering a systematic approach. This randomized, single-blind controlled trial aimed to assess the effectiveness of an app-based therapeutic in improving ED.
METHODS: A total of 241 patients (49.74, standard deviation 12.73 yr) with ED (International Index of Erectile Function [IIEF]-5 <22) were randomized to the 12-wk app-based therapy (treatment group [TG], n = 122) or a waiting list for the app with continuation of their current management protocol (control group [CG], n = 119). Patients on long-term medication for ED were included, but subsequent exclusion occurred for those starting new medication. Coprimary endpoints were improvements from baseline to 12 wk in erectile function (IIEF-5), disease-related quality of life (QOL-Med-15), and patient activation (Patient Activation Measure [PAM-13]).
UNASSIGNED: Erectile function (IIEF-5) improved by 4.5 points in the TG versus 0.2 points in the CG (p < 0.0001, 95% confidence interval [CI] 3.4-5.0) group. Quality of life (QOL-Med) improved by 20.5 points in the TG versus -0.0 points in the CG (p < 0.0001, 95% CI 19.2-26.0) group. Patient activation (PAM-13) improved by 11.2 points in the TG versus 0.6 points in the CG (p < 0.0001, 95% CI 9.1-13.6) group. Phosphodiesterase type 5 inhibitor intake had no influence on all observed treatment effects.
CONCLUSIONS: App-based therapy of patients with ED provided a significant, clinically meaningful improvement. Quality of life and patient activation were also enhanced significantly. This program has the potential to change clinical practice in the treatment of ED.
RESULTS: A therapy app improved sexual function and overall well-being for men experiencing erectile dysfunction, leading to better quality of life.

Erectile dysfunction is common among older men and has been associated with low serum 25-hydroxy vitamin D concentration. However, this association may be due to uncontrolled confounding, and there is a paucity of evidence from interventional studies. We aimed to examine the effect of vitamin D supplementation on the prevalence of erectile dysfunction, in an exploratory analysis using data from a large randomized controlled trial.
The D-Health Trial recruited Australians aged 60-84 years between January 2014 and May 2015 and randomly assigned them to supplementation with 60,000 IU of vitamin D or placebo per month for up to 5 years. Blood samples were collected annually from randomly selected participants (total N = 3943). We assessed erectile dysfunction at the end of the third year of follow-up. We used log-binomial regression to examine the effect of vitamin D on the prevalence of erectile dysfunction overall, and within sub-groups.
Of the 11,530 men enrolled, 8920 (77.4 %) completed the erectile dysfunction question and were included in the analysis. After three years of supplementation, the mean serum 25-hydroxy vitamin D concentration was 76 nmol/L (standard deviation (SD) 24.94) in the placebo group and 106 nmol/L (SD 26.76) in the vitamin D group (p < 0.0001). The prevalence of erectile dysfunction was 58.8 % and 59.0 % in the vitamin D and placebo groups, respectively (prevalence ratio 1.00, 95 % CI 0.97, 1.03); there was no evidence of an effect of vitamin D in any subgroup analyses.
Supplementing older men with vitamin D is unlikely to prevent or improve erectile dysfunction.
(ACTRN12613000743763).

BACKGROUND: Psychological inflexibility is a core concept of acceptance and commitment therapy (ACT), which is a comprehensive, transdiagnostic interpretation of mental health symptoms. Erectile dysfunction (ED) is a condition that affects male sexual performance, involving the inability to achieve and maintain a penile erection sufficient for satisfactory sexual activity. Psychosocial factors primarily influence ED in men younger than 40 years, whereas biological factors are more likely to be the underlying cause in older men.
OBJECTIVE: This web-based cross-sectional study examined differences in depression, anxiety, and psychological inflexibility among men with ED younger and older than 40 years in a Japanese population.
METHODS: We used a web-based survey to gather data from various community samples. ED was assessed by the International Index of Erectile Function-5 (IIEF-5) questionnaire, while depression, anxiety, and psychological inflexibility were evaluated by the Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Acceptance and Action Questionnaire-II (AAQ-II), Cognitive Fusion Questionnaire (CFQ), and Valuing Questionnaire-Obstacle Subscale (VQ-OB) questionnaires. The chi-square test estimated the scores of PHQ-9 and GAD-7 among men with ED, comparing those younger than 40 years and those older than 40 years. Additionally, a two-way ANOVA was conducted with ED severity and age group as independent variables, assessing psychological inflexibility.
RESULTS: Valid responses from 643 individuals (mean age 36.19, SD 7.54 years) were obtained. Of these, 422 were younger than 40 years (mean age 31.76, SD 5.00 years), and 221 were older than 40 years (mean age 44.67, SD 2.88 years). There was a statistical difference in the prevalence of depression as judged by PHQ≥10 between men with ED younger and older than 40 years (P<.001). On the other hand, there was no difference in the prevalence of anxiety as judged by GAD≥10 (P=.12). The two-way ANOVA revealed that the interactions for CFQ (P=.04) and VQ-OB (P=.01) were significant. The simple main effect was that men with ED younger than 40 years had significantly higher CFQ (P=.01; d=0.62) and VQ-OB (P<.001; d=0.87) scores compared to those older than 40 years in moderate ED and severe ED. Additionally, it was found that men younger than 40 years with moderate to severe ED had significantly higher CFQ (P=.01; d=0.42) and VQ-OB (P=.02; d=0.38) scores compared to men younger than 40 years without ED. On the other hand, no interaction was found for AAQ-II (P=.16) scores.
CONCLUSIONS: To the best of our knowledge, this web-based cross-sectional study is the first to examine the relationship between psychological inflexibility and ED. We conclude that men with moderate and severe ED younger than 40 years have higher psychological inflexibility and might be eligible for ACT.

Amniotic tissues and methylene blue (MB) provide the ability for neuroregeneration, and MB enables intraoperative neurostaining. We first combined the techniques to explore a neuroprotective effect on early functional outcomes in a retrospective proof-of-concept trial of 14 patients undergoing radical prostatectomy (RP). The patients were followed up at a median of 13 months, and the continence and potency rates were reported. Early recovery of continence was found after three months. No effect on potency was detected. The findings indicate the feasibility of this tissue-engineering strategy, and justify prospective comparative studies.

BACKGROUND: Only few studies have assessed sexual dysfunction in men with Klinefelter syndrome (KS).
OBJECTIVE: To define pooled prevalence estimates and correlates of erectile dysfunction (ED) and decreased libido (DL) in KS.
METHODS: A thorough search of Medline, Embase and Web of Science was performed to identify suitable studies. Quality of the articles was scored using the Assessment Tool for Prevalence Studies. Data were combined using random effect models and the between-studies heterogeneity was assessed by the Cochrane\'s Q and I2. The sources of heterogeneity were investigated by meta-regression and sub-group analyses. Funnel plot, Begg\'s rank correlation and trim-and-fill test were used to assess publication bias.
METHODS: The pooled prevalence of ED and DL in KS as well as 95% confidence intervals (CIs) were estimated from the proportion of cases of sexual dysfunction and the sample size. Variables that could affect the estimates were identified by linear meta-regression models.
RESULTS: Sixteen studies included collectively gave information about ED and DL in 482 and 368 KS men, respectively, resulting in a pooled prevalence of 28% (95% CI: 19%-36%) for ED and 51% (95% CI: 36%-66%) for DL, with a large heterogeneity. The trim-and-fill adjustment for publication bias produced a negligible effect on the pooled estimates. At the meta-regression analyses, a higher prevalence of ED was significantly associated with an older age but not with lower testosterone levels. In series with a mean age >35 years, the ED prevalence estimate increased up to 38% (95% CI: 31%-44%) with no heterogeneity (I2=0.0%, P=0.6). On the contrary, the prevalence of DL increased significantly as testosterone levels decreased, without a significant relationship with age.
CONCLUSIONS: While DL would largely reflect an androgen deficiency, in older men with KS, erectile function should be assessed irrespective of testosterone levels.
UNASSIGNED: This is the first meta-analysis defining pooled prevalence estimates and correlates of ED and DL in KS. Nevertheless, caution is required when interpreting results, due to the high risk of bias in many studies, as well as the dearth of data about psychosocial and/or psychosexological variables and age at the diagnosis.
CONCLUSIONS: ED and DL represent common clinical complaints in KS. While the prevalence of ED would increase with age, DL gets more common as serum testosterone decreases. Further studies are warranted to elucidate the pathogenetic mechanism(s) underlying the age-dependent increase in the prevalence of ED, apparently unrelated to the androgenic status.

BACKGROUND: Whether and to what extent an association exists between hyperuricemia and erectile dysfunction (ED) has not yet been fully determined.
OBJECTIVE: To define pooled prevalence estimates and correlates of erectile dysfunction in men with hyperuricemic disorders.
METHODS: A thorough search of Medline, Scopus, and Cochrane Library databases was performed. Data were combined using random-effects models and the between-study heterogeneity was assessed by Cochrane\'s Q and I2 tests. A funnel plot was used to assess publication bias.
RESULTS: Overall, 8 studies included gave information about 85,406 hyperuricemic men, of whom 5023 complained of erectile dysfunction, resulting in a pooled erectile dysfunction prevalence estimate of 33% (95% Confidence Interval: 13-52%; I² = 99.9%). The funnel plot suggested the presence of a publication bias. At the meta-regression analyses, among the available covariates that could affect estimates, only type 2 diabetes mellitus was significantly associated with a higher prevalence of erectile dysfunction (β = 0.08; 95% Confidence Interval: 0.01, 0.15, p = 0.025). At the sub-group analysis, the pooled erectile dysfunction prevalence decreased to 4% (95% Confidence Interval: 0%-8%) when only the largest studies with the lowest prevalence of type 2 diabetes mellitus were included and increased up to 50% (95% Confidence Interval: 17%-84%) when the analysis was restricted to studies enrolling smaller series with higher prevalence of type 2 diabetes mellitus.
CONCLUSIONS: A not negligible proportion of men with hyperuricemia can complain of erectile dysfunction. While a pathogenetic contribution of circulating uric acid in endothelial dysfunction cannot be ruled out, the evidence of a stronger association between hyperuricemia and erectile dysfunction in type 2 diabetes mellitus points to hyperuricemia as a marker of systemic dysmetabolic disorders adversely affecting erectile function.

Only few studies have assessed sexual dysfunction in men with Klinefelter syndrome (KS).
To define pooled prevalence estimates and correlates of erectile dysfunction (ED) and decreased libido (DL) in KS.
A thorough search of Medline, Embase and Web of Science was performed to identify suitable studies. Quality of the articles was scored using the Assessment Tool for Prevalence Studies. Data were combined using random effect models and the between-studies heterogeneity was assessed by the Cochrane\'s Q and I2. The sources of heterogeneity were investigated by meta-regression and sub-group analyses. Funnel plot, Begg\'s rank correlation and trim-and-fill test were used to assess publication bias.
The pooled prevalence of ED and DL in KS as well as 95% confidence intervals (CIs) were estimated from the proportion of cases of sexual dysfunction and the sample size. Variables that could affect the estimates were identified by linear meta-regression models.
Sixteen studies included collectively gave information about ED and DL in 482 and 368 KS men, respectively, resulting in a pooled prevalence of 28% (95% CI: 19%-36%) for ED and 51% (95% CI: 36%-66%) for DL, with a large heterogeneity. The trim-and-fill adjustment for publication bias produced a negligible effect on the pooled estimates. At the meta-regression analyses, a higher prevalence of ED was significantly associated with an older age but not with lower testosterone levels. In series with a mean age >35 years, the ED prevalence estimate increased up to 38% (95% CI: 31%-44%) with no heterogeneity (I2=0.0%, P=0.6). On the contrary, the prevalence of DL increased significantly as testosterone levels decreased, without a significant relationship with age.
While DL would largely reflect an androgen deficiency, in older men with KS, erectile function should be assessed irrespective of testosterone levels.
This is the first meta-analysis defining pooled prevalence estimates and correlates of ED and DL in KS. Nevertheless, caution is required when interpreting results, due to the high risk of bias in many studies, as well as the dearth of data about psychosocial and/or psychosexological variables and age at the diagnosis.
ED and DL represent common clinical complaints in KS. While the prevalence of ED would increase with age, DL gets more common as serum testosterone decreases. Further studies are warranted to elucidate the pathogenetic mechanism(s) underlying the age-dependent increase in the prevalence of ED, apparently unrelated to the androgenic status. A Barbonetti, S D\'Andrea, W Vena, et al. Erectile Dysfunction and Decreased Libido in Klinefelter Syndrome: A Prevalence Meta-Analysis and Meta-Regression Study. J Sex Med 2021;18:1054-1064.

Phosphodiesterase type 5 inhibitors represent the standard treatment of erectile dysfunction after nerve-sparing prostatectomy. Avanafil is a second-generation phosphodiesterase type 5 inhibitor with a high selectivity for phosphodiesterase type 5 isoform. To date, there are no studies comparing the outcomes of avanafil versus sildenafil in this scenario. In this study, we evaluated the efficacy and safety of avanafil versus sildenafil as a drug for post-prostatectomy rehabilitation. Overall, 160 patients submitted to robot-assisted nerve-sparing prostatectomy for localized prostate cancer at three hospitals were enrolled for the present study. After 6 months of treatment, patients in the two groups showed no significantly different sexual function scores, except for the Erection Hardness Score and Sexual Encounter Profile-Q2 that were higher in the Sildenafil group. Adverse events in the Avanafil group occurred in four (5%) patients and in 16 (20%) patients in the Sildenafil group. According to our experience, in patients undergoing nerve-sparing prostatectomy, penile rehabilitation with avanafil compared to sildenafil showed a lower ability to produce a valid erection in the initial phase of sexual intercourse, a difference that disappears in the continuation of the same. Avanafil showed a greater tolerance profile with a lower rate of AEs and discontinuation of therapy due to AEs.

The aim of this study was to expand existing literature on the effects of cardiovascular risk factors on the outcome of low-intensity extracorporeal shockwaves therapy (LIESWT), and to evaluate the role of hormone concentrations. Twenty patients with long-standing, PDE5i-resistant, vasculogenic erectile dysfunction (VED) were treated with six weekly sessions of LIESWT (9000 pulses). After a three-week break, four poor responders underwent another six weekly sessions. Rigidity score (RS) questionnaire was administered at baseline (T0), last session (T1), and three months after LIESWT (T2), while the Improvement component of the Clinical Global Impression of Change (CGIC-I) and the International Index of Erectile Function-5 (IIEF-5) questionnaires were administered at T1 and T2, and at T0 and T2, respectively. At T0 serum luteinizing hormone (LH), testosterone, sex hormone binding globulin (SHBG), calculated free testosterone, and prolactin levels were also recorded. At T1 and T2, 12/20 (60%) and 11/20 (55%) patients reached a RS ≥ 3; 16/20 (80%) and 13/20 (65%) improved their erections variably. Testosterone levels correlated positively with CGIC-I at T1. Patients < 65 years and those nonhypercholesterolemic had higher RS at T1 and T2. Age correlated negatively with RS at T1 and T2. At T0, diabetic patients had lower IIEF-5 scores, but those with RS ≥ 3 at T1 had higher IIEF-5 compared to those with RS < 3. Also, diabetes duration correlated inversely with IIEF-5 at T0. At T2, IIEF-5 improved significantly by an average of 2.8-points. We confirm safety and effectiveness of LIESWT for the treatment of VED. Age ≥ 65 years, diabetes, and hypercholesterolemia influence early and negatively the outcome of LIESWT.

Although clinical studies using stem cells to treat erectile dysfunction have been performed or are ongoing, there is little consensus on the optimal protocol. We aimed to develop a protocol optimizing human bone marrow-derived mesenchymal stromal cell (hBMSC) therapy in a rat model of cavernous nerve injury.
We performed, in order, a dose-finding study, a toxicokinetic study of hBMSCs, and a study to determine the timing and number of cell injections.
From the dose-finding study, 1 × 10(6) cells were selected as the dose per hBMSC injection. From the toxicokinetic study, 14 days was selected as the interval between repeat treatments. In the final study, the ratio of maximal intracavernous pressure to mean arterial pressure was significantly lower in the control group than in the sham group (23.4% vs. 55.1%, P <0.001). An immediate single injection of hBMSCs significantly improved erectile function compared with the control group (39.8%, P = 0.035), whereas a delayed single injection showed improvement with a marginal trend (38.1%, P = 0.079). All histomorphometric changes were significantly more improved in the immediate or delayed single injection groups than in the control group. Repeat treatments did not provide any benefit for the recovery of erectile function and histomorphometric changes.
Intracavernous injection of 1 × 10(6) hBMSCs results in a recovery of penile erection and histomorphometric changes in a rat model of cavernous nerve injury, even when treatment was delayed until 4 weeks after cavernous nerve injury.