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Introduction: There is a rising concern about developing innovative, efficacious PDE5I molecules that provide better safety, efficacy, and tolerability with less adverse effects. Innovative PDE5I with dual targets have also been defined in the literature. Additionally, some of PDE5I are able to selectively inhibit other enzymes such as histone deacetylase, acetylcholine esterase, and cyclooxygenase or act as nitric oxide donors. This review presents knowledge concerning the advanced trends and perspectives in using PDE5I in treatment of ED and other conditions., Areas Covered: Pre-clinical and early clinical trials that investigated the safety, efficacy, and tolerability of novel PDE5I such as Udenafil, Mirodenafil, Lodenafil, Youkenafil, Celecoxib, and TPN729 in treatment of ED and other conditions., Expert Opinion: Preclinical and limited early clinical studies of the new molecules of PDE5I have demonstrated encouraging results; however, safety, efficacy, and tolerability are still issues that necessitate further long-term multicenter clinical studies to ensure justification of their uses in treatment of ED and other conditions. Progress in molecular delivery techniques and tailored patient-specific management and additional therapeutic technology will dramatically improve care for ED and other conditions. The dream of ED and many other conditions becoming more effectively managed may be feasible in the near future.

Background: Several reports showed that sexual function was affected during and after the COVID-19 pandemic., Aims: The objective of the study was to demonstrate whether a realistic association exists between the COVID-19 pandemic and erectile dysfunction (ED) among a sampled Egyptian population in Damietta governorate., Methods: This cross-sectional study consisted of 330 adult males diagnosed with COVID-19 infection. They were categorized in three age groups (18-29, 30-39, and 40-50 years, respectively). COVID-19-confirmed cases were assessed by the Arabic version of the International Index of Erectile Function questionnaire (IIEF) scores., Results: The prevalence of ED according to the IIEF was 55.1%. The ED was categorized into mild ED which represents 25.8% of the patients, mild to moderate which represents 22.4% of the patients, moderate which represents 7% of the patients, and severe which represents 0% of the patients. We found a significant negative correlation between the age of the patients and the IIEF score. Also, we found an association between the severity of COVID-19 infection and the IIEF score., Conclusion: An association of new-onset ED in men who suffered COVID-19 infection was established. This may be due to virus-induced endothelial cell dysfunction; however, an underlying mechanism and causation have not yet been clearly elucidated. While it appears that COVID-19 infection may be a risk factor for ED, additional research is needed to establish causality., (© 2024. The Author(s).)

Objective: The association between alcohol use and erectile dysfunction (ED) has not been explored adequately. The aim of this study is (i) to determine the prevalence of ED in patients with Alcohol use disorder (AUD), (ii) the association of ED with sociodemographic and clinical variables, (iii) the association between severity of drinking and sociodemographic and clinical variables, and (iv) the assess the change in ED after one month of abstinence from alcohol., Methods: 203 consecutive patients were recruited into the study after taking written informed consent. Sociodemographic data was collected using a proforma and ED was assessed using International Index of Erectile Function-5 (IIEF-5). The patients were also followed up after 1 month of abstinence to assess the change in erectile function., Results: The prevalence of ED was 68.5%. Out of the 203 subjects, 28.1% had mild ED, 24.1% had mild to moderate ED, 9.9% had moderate ED and 6.4% had severe ED. Significant association were seen between ED and age, marital status, diabetes mellitus, hypertension, total duration, and severity of drinking. A significant association was seen between severity of drinking and age, diabetes mellitus, hypertension, alcoholic liver disease, tobacco use and duration of drinking. The improvement in ED after 1 month abstinence was found to be significant., Conclusions: ED is a common problem in patients with AUD. Routine assessment of sexual functioning is warranted in patients with AUD and the information that ED improves with abstinence can provide an impetus to change.

Background & Aims: 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., Methods: 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., Results: 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., Conclusion: Supplementing older men with vitamin D is unlikely to prevent or improve erectile dysfunction., Clinical Trials Registry: (ACTRN12613000743763)., Competing Interests: Declaration of competing interest PW has funding from Astra Zeneca for an unrelated study of ovarian cancer. PE reports grants and other from Amgen and Alexion, grants from Sanofi, and other from Pfizer, ASBMR, IOF, and APCO Healthy Bones Australia. DW reports speaker payment from Pierre Fabre Australia. MR reports consulting fees from BXTAccelyon and other with Bayer. All other authors declare no competing interests., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Sexual dysfunction is a multifactorial health condition characterized by distressing disturbances in the sexual response and libido, leading to an inability to maintain penile erection and achieve pleasure. Considering the huge Brazilian biodiversity, many plants are traditionally used for aphrodisiac purposes. However, the use of native medicinal plants as sexual boosters in Brazil has been poorly studied., Aim of the Study: This review focuses on the composition, pharmacology, and results of experimental trials of the main native plants used in Brazilian folk medicine with alleged aphrodisiac effects. We aimed to provide a state-of-the-art reference for research on herbs for the treatment of male sexual dysfunction by summarizing and discussing the main studies found., Materials and Methods: The relevant information was collected by searching keywords (aphrodisiac, sexual tonic, sexual stimulant, sexual vigor stimulant, sexual impotency, erectile dysfunction, etc.) from books containing primary surveys conducted in the original communities and bibliographic surveys prepared by authors linked to the national academic and scientific environment edited in Brazil. Preclinical and clinical studies of the compiled plant species were performed using scientific databases (Scopus, PubMed, SciELO, and SciFinder)., Results: Seventy-four plant species belonging to 44 families used in Brazil to treat sexual dysfunction were compiled from ethnopharmacological literature. Fourteen plants, including Pfaffia glomerata (Spreng.) Pedersen, Aspidosperma quebracho-blanco Schltdl., Anemopaegma arvense (Vell.) Stellfeld ex de Souza, Mimosa pudica L., Heteropterys tomentosa A. Juss., Trichilia catigua A. Juss., and Turnera diffusa Willd. ex Schult. were pharmacologically studied to confirm these therapeutic properties. Probable modes of action include antioxidant and androgenic activities, inhibition of the PDE5 enzyme, increase in NO levels, and activation of dopaminergic and noradrenergic pathways. In addition, several different species popularly known as "catuaba" were identified, leading to adulterations and controversial effects., Conclusion: The overall results of the present review of Brazilian folk literature reveal that Brazil has a long tradition of using plants with potential aphrodisiac effects. However, further research is required to identify, characterize, and standardize the active ingredients and herbal preparations used in aphrodisiacs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Erectile dysfunction (ED), for multifactorial reasons, is one of the biggest current quandaries among men worldwide and results in other complications such as reduced quality of life of the patient and his sexual partner, impotence, and psychiatric problems., Objectives: Understanding of disease etiology, penile anatomy, erectile physiology, therapeutic mechanisms, and effective molecular pathways all play key roles in determining a therapeutic approach. This project is based on the study of topical minoxidil's effectiveness in treating ED., Methods: To perform a comprehensive overview of the subject, we performed a triple-keyword combination search to assess recent studies of ED., Results: The most common formulation used in these studies was 2% minoxidil solution. Except for cases studied in paralytic patients, topical treatment with minoxidil appears to elicit a mild erectile response; however, this finding is insufficient to confirm the effectiveness of this topical treatment., Conclusions: Although evidence to confirm the therapeutic properties of minoxidil in ED is limited, combination therapy and the use of modern formulations of minoxidil are promising options for treating ED in the future., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: This study aimed to review recent evidence on conservative non-surgical options for erectile dysfunction (ED) in men. A narrative review of the literature was performed. A comprehensive search in the MEDLINE, Embase, and Cochrane databases was done. Papers in English language, published from May 2017 until May 2022, were included. Papers reporting basic research or animal research were excluded, as long as reviews or meta-analyses. Congress reports, clinical cases, or clinical trials protocols with no results were also excluded., Recent Findings: We found a multitude of different treatment modalities for ED. We must take into account the type of patient, their comorbidities, the origin of their ED, and its severity in order to reproduce effective results using these therapies. Some of the treatments show good results with a good level of evidence (new IPDE5 formulations, intracavernous injections, shock wave therapy, hormonal theraphy, psycho-sexual theraphy). However, others (some new molecules, stem cell theraphy, platelet-rich plasma injections, oxygenation-based therapy, nutraceuticals), although some of them present promising results, require randomized studies with a larger number of patients and a longer follow-up time to be able to establish firm recommendations. Regarding the conservative treatment of erectile dysfunction, in recent years, some therapies have been consolidated as effective and safe for certain types of patients. On the other hand, other treatment modalities, although promising, still lack the evidence and the necessary follow-up to be recommended in daily practice., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To apply a new review methodology, called reverse systematic review (RSR), to assess how different classification criteria can influence erectile dysfunction rates in patients undergoing laparoscopic radical prostatectomy (LRP)., Methods: We used RSR from January 1, 2000, until December 31, 2020. The post-prostatectomy erectile dysfunction (PPED) rates were evaluated at 1, 3, 6, 12, and 18 months after surgery in different criteria selected as the most commonly used and divided into four groups: "Erection Sufficient for Intercourse (ESI)", "IIEF-5 > 17", "IIEF-5 > 22" and "Not Available". Temporal distribution of different criteria was analyzed to identify patterns throughout the "natural history" of LRP., Results: 40 systematic reviews on LRP evaluated 81 cohorts and 21,618 patients on PPED. ESI was the predominant form of PPED evaluation (75.3%) followed by IIEF-5 > 22 (11.1%). Despite being a simpler criterion, ESI showed worse PPED rates at 1, 3, 6 and 12 months (8%, 27%, 43% and 51%) than IIEF-5 > 22 (14%, 26%, 45% and 58%). The studies were published between 2005 and 2015, but it was in 2010 that the ESI criterion was established as predominant in the literature, reducing the application of others., Conclusion: The RSR has proven effective in demonstrating how the PPED evaluation criteria behaved in the "natural history" of the LRP. It showed how a simple and easy-to-apply criterion, such as the ESI, was preferred by the authors, even showing worse PPED rates than other more complex., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: In a systematic data analysis, we evaluated the influence of a digital health app on erection scores as well as life quality and patient activation in a group of patients with erectile dysfunction., Methods: In all, 44 participants took part in an evidence-based program for patients with erectile dysfunction. The in app 12-week program included pelvic floor exercises and physiotherapeutic and cardiovascular training. In addition, there where sessions on mindfulness and sexual therapy as well as useful information about erectile dysfunction and its causes, nutrition, and risk factors. The median age was 46 years (19-75 years). All patients answered IIEF‑5, PAM-13 and QoL-Med questionnaires at the beginning and the end of the program. A total of 27 questionnaires could be evaluated at both times., Results: The average improvement in IIEF‑5 score was 4.5 points (p < 0.0001). 96% of patients showed overall improvement of erection scores. Improvement in life quality was shown in 93% of participants. Moreover, there was a significant increase in patient activation scores., Conclusion: We were able to show that a multimodal digital app for self-management of erectile dysfunction improved not only erection scores but also life quality and patient activation. We concluded that it is possible to reproduce results of analog studies in a digital setting. Digital solutions can help to include patients in their treatment and to put guideline suggestions into practice., (© 2022. The Author(s).)

The purpose of this study was to evaluate and anticipate the outcome of daily use of tadalafil in patients with erectile dysfunction using elastography. 183 volunteers and 183 patients with erectile dysfunction were included. Pretreatment SWE readings for our patients were calculated with a linear probe. IIEF score Q was measured once at the start of the study for volunteers and twice for patients, one prior to the start of tadalafil administration and the other on one year of 5 mg daily tadalafil after the second post-washout (one month post-treatment stopped). There was no significant difference between patients and volunteers in mean age or risk factors except in SWE values as mean SWE of volunteers was 14.03 ± 1.54 kpasc, while mean SWE of patients was 21.278 ± 8.228 kpasc. The presence of comorbid diabetes, severe disease and pre-SWE ≥23.635 was significantly associated with poor outcome. We conclude that penile SWE could be useful to select probable good responders for a continuous tadalafil use, thus avoiding the unnecessary cost and time in non-responders., (© 2022 Wiley-VCH GmbH.)

Background: There is a compelling evidence for the relation between alcohol use and erectile dysfunction (ED), however the impact of alcohol abstinence on improvement of ED is explored sparsely., Aim: This study aimed to determine the impact of alcohol abstinence on ED. The association between total duration of drinking, the quantity of alcohol consumed, sociodemographic, clinical variables and ED were also studied., Methods: One hundred and four subjects with alcohol use disorder and complaints of ED meeting the inclusion and exclusion criteria were recruited into the study after taking written informed consent. The subjects were assessed at baseline and after 3 months of abstinence from alcohol with IIEF-5 and a specially designed pro forma. Wilcoxon signed rank test was used to assess the change in ED after 3 months of abstinence. Chi square test was done to assess the associations and binary logistic regression was done to determine the significance of variables after 3 months of abstinence., Outcomes: Improvement in ED after 3 months of abstinence from alcohol and its association between socio demographic and clinical variables were assessed., Results: Of the 104 subjects studied, 88.5% (92) showed improvement in ED after 3 months of abstinence from alcohol. Wilcoxon signed rank test showed that the improvement in ED after 3 months of abstinence was significant. (Z = 8.708, P < .001). Significant association was found between age, alcoholic liver disease, total duration of drinking, and number of standard drinks per day with ED after 3 months of abstinence., Clinical Implications: Information that ED will improve with abstinence from alcohol can be used in deaddiction treatment to provide a motivation for change., Strength and Limitations: This study aims to fill the gap in literature as only a few studies have examined the impact of abstinence from alcohol on ED. The main limitations of this study are short follow up period and since this study was conducted in a tertiary care hospital it could have given rise to Berksonian bias., Conclusion: Results indicate that ED shows improvement with abstinence from alcohol. Absence of alcoholic liver disease, younger age, shorter duration of drinking, lesser number of standard drinks per day had a significant influence in the improvement of ED with alcohol abstinence and this information can be beneficial in treatment to provide an impetus for change. Karunakaran A., Michael J. P. The Impact of Abstinence From Alcohol on Erectile Dysfunction: A Prospective Follow up in Patients With Alcohol Use Disorder. J Sex Med 2022;19:581-589., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

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., Materials and 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 I 2 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., (© 2021 American Society of Andrology and European Academy of Andrology.)

We aimed to evaluate ten-year outcomes of penile prosthesis (PP) implantation for the treatment of erectile dysfunction and to assess predictors of early prosthetic infection (EPI). We identified 549 men who underwent 576 PP placements between 2008 and 2018. Univariate and multivariate analyses were used to identify potential predictors of EPI. An EPI predictive nomogram was developed. Thirty-five (6.1%) cases of EPI were recorded with an explant rate of 3.1%. In terms of satisfaction, 82.0% of the patients defined themselves as "satisfied," while partner's satisfaction was 88.3%. Diabetes (P = 0.012), longer operative time (P = 0.032), and reinterventions (P = 0.048) were associated with EPI risk, while postoperative ciprofloxacin was inversely associated with EPI (P = 0.014). Rifampin/gentamicin-coated 3-piece inflatable PP (r/g-c 3IPP) showed a higher EPI risk (P = 0.019). Multivariate analyses showed a two-fold higher risk of EPI in diabetic patients, redo surgeries, or when a r/g-c 3IPP was used (all P < 0.03). We showed that diabetes, longer operative time, and secondary surgeries were the risk factors for EPI. Postoperative ciprofloxacin was associated with a reduced risk of EPI, while r/g-c 3IPP had higher EPI rates without an increased risk of PP explant. After further validation, the proposed nomogram could be a useful tool for the preoperative counseling of PP implantation., Competing Interests: None

The science of penile erection, including recent advances in its molecular physiology and neuroanatomic pathways, is described. The pathophysiology of erectile dysfunction is presented, acknowledging associated disease states, and accordingly follows a practical classification scheme: vasculogenic, neurogenic, endocrine, and psychogenic., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Erectile dysfunction management is intended to restore capacity for penile erection. Although effective, none of the currently available treatments approved by the US Food and Drug Administration reverse erectile dysfunction pathophysiology. Penile arterial bypass surgery is intended to restore erectile function without the need for the chronic use of vasoactive medications or penile prosthesis placement. In select cases, venous ligation surgery may be beneficial, but this approach is not supported by the most recent guidelines on erectile dysfunction management. The lack of high-quality research surrounding penile vascular surgery has limited its use., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Erectile dysfunction (ED) is a common condition encountered by an array of subspecialists and is the most cited research topic within the field of andrology. This bibliometric analysis aims to identify the most influential papers that inform current clinical practice and likely shape future research. The Thompson Reuters Web of Science citation database was interrogated using search terms to cover the breadth of erectile dysfunction. Results were ranked according to citation number with country of origin, journal, topic, year of publication, author and institution also analysed. The search criteria matched 12,570 manuscripts. The top 100 highest citation ranged from 3013 to 161 (median 229.5). The most cited manuscript reports the prevalence and risk factors of ED within the Massachusetts Male Aging Study. The most manuscripts were published by the Journal of Urology ( n  = 15) with a total of 7913 citations. Institutions from the USA contributed the majority ( n  = 55) with the UK ( n  = 14) second. The most common theme represented was epidemiology ( n  = 46) followed by treatment ( n  = 27). This analysis provides a list of the most influential manuscripts within ED and illustrates what can be considered a 'highly citable' paper. The most influential papers in Erectile Dysfunction remain seminal works from the end of the last century. The most cited manuscript has been cited 194 times in the last 17 months showing its continued value. Only one paper published within the last decade has reached the top twenty exemplifying the relative lack of novel influential publications.

Nonalcoholic fatty liver disease (NAFLD) is one of the risk factors for erectile dysfunction (ED). We aimed to predict the risk of ED in patients with NAFLD. The study included 146 male patients complaining impotence admitted to the urology outpatient clinic aged 24-80 years without a history of alcohol use who underwent abdominal ultrasonography between February 2018 and January 2019. 106 patients with NAFLD and 40 men without NAFLD were included in the study. Clinical and laboratory parameters, ED status according to International Index of Erectile Function-5 were compared between patients with and without NAFLD. The mean age of patients was 51.47 ± 10.34 years. NAFLD was detected in 72.6% of the patients. No statistically significant difference was found regarding mean age, BMI, IIEF-5 scores, DM status, serum glucose levels (p > .05). Fasting insulin levels, hypertension (HT), insulin resistance (IR) and ED status of the patients with NAFLD were significantly higher than patients without NAFLD (p < .05). NAFLD was found to be a significantly independent associated with ED. We also found that patients with NAFLD have risk of ED 2.92 times higher than without NAFLD (OR: 2.92). For the patients presenting with erectile dysfunction, hepatic steatosis should also be considered., (© 2021 Wiley-VCH GmbH.)

Professor Wang Qi, an academician of the Chinese Academy of Engineering and the founder of andrology of traditional Chinese medicine (TCM), has been engaged in theoretical and clinical researches on andrology of TCM for many years. Erudite and well-experienced, he advanced the idea of "treating impotence from the liver" and unique theories of TCM therapies for male diseases, with ingenuity and originality in clinical medication, proficient in using small and precise prescriptions to achieve high efficacy. This article summarizes and discusses the authors' experience in Professor Wang Qi's clinic learning from him his academic thought and medication philosophy in the treatment of secondary ED.

Based on the data mining technology, the rules of acupoint selection and prescription were analyzed for impotence treated with acupuncture and moxibustion in ancient recorded in Zhonghua Yidian . By taking " yangwei " and " yinwei " as the searching terms, the database of Zhonghua Yidian (the 5th edition) were retrieved and the relevant information of impotence, such as prescription provision, acupoints and use frequency were extracted. Using the software, e.g. Microsoft Excel and Weka 3.8.4, the rules of acupoint selection and prescription for impotence treated with acupuncture and moxibustion in ancient were analyzed. Fifty five provisions of acupoint prescriptions were in compliance with the requirements and screened. Of them, there were 17 compound prescriptions and the rest were the single-point prescriptions, with 24 acupoints involved. Regarding the use frequency of acupoints in treatment of impotence, the top 5 acupoints were Yingu (KI 10), Ququan (LR 8), Qichong (ST 30), Taichong (LR 3) and Rangu (KI 2). The cluster analysis found that Yingu (KI 10), Ququan (LR 8)-Qichong (ST 30), Taichong (LR 3)-Rangu (KI 2)-Xingjian (LR 2), and Mingmen (GV 4)-Zhongfeng (LR 4)-Yuji (LU 10)-Yanggu (SI 5) were formed the group prescriptions respectively. Multilayer correlation analysis discovered that the commonly used meridians were the liver meridian of foot- jueyin , the kidney meridian of foot- shaoyin , the stomach meridian of foot- yangming and the conception vessel. The acupoints selected were generally on the lower extremities, the abdomen and the upper extremities. Regarding the special points, the five- shu points and the convergent points were mostly involved. By the analysis on compound prescriptions, 3 patterns of acupoint combination were discovered, the prescription by taking Yingu (KI 10), Rangu (KI 2) and Zhongfeng (LR 4) as the key points, the one by taking Shenshu (BL 23) and Yanggu (SI 5) as the key points and the relevant fixed combination of 4 acupoints, including Taichong (LR 3), Xingjian (LR 2), Neiting (ST 44) and Xiangu (ST 43). By the analysis on the compound prescriptions, 3 common meridian combinations were found, including the combination with the kidney meridian predominated, the relevant fixed combination with the liver meridian and the stomach meridian and the one with small intestine meridian and the lung meridian.

Background: Only few studies have assessed sexual dysfunction in men with Klinefelter syndrome (KS)., Aim: 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 I 2 . 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., Main Outcome Measure: 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 (I 2 =0.0%, P=0.6). On the contrary, the prevalence of DL increased significantly as testosterone levels decreased, without a significant relationship with age., Clinical Implications: While DL would largely reflect an androgen deficiency, in older men with KS, erectile function should be assessed irrespective of testosterone levels., Strength & Limitations: 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. 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., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

The objective of this study is to investigate the association between periodontitis (PD) and erectile dysfunction (ED).A systematic review and meta-analysis on data was extracted and conducted according to PRISMA. Relevant articles were selected from a literature search using MEDLINE, EMBASE, Scopus, Web of Science and CENTRAL from inception until August 2, 2020. Both randomized and nonrandomized controlled studies were included. Case reports, case series, nonsystematic reviews and trials published as abstract were excluded. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to estimate the association between PD and the risk of ED. The meta-analysis was conducted with RevMan 5.3. Methodological quality assessment was carried out using the Newcastle-Ottawa Quality Assessment Scale and the quality of evidence was assessed using the GRADE approach.Six articles (215008 subjects) were included for analysis. Of the participants, 38,675 cases were compared to 1,76,333 healthy controls. Based on the random effects model, periodontitis was associated with an increased risk of ED (OR = 2.56, 95% CI: 1.70-3.85) as compared with the non-periodontitis individuals. The findings were statistically significant with a p < .0001. The statistical heterogeneity was high across all studies ( I 2 = 98%, p < .00001). Estimates of total effects were generally consistent with the sensitivity and subgroup analyses.Within the limits of the available evidence, our review and meta-analysis showed that a significant association exists between the PD and ED. The results should be interpreted with caution due to high degree of inconsistency across all the studies.

Introduction: Numerous factors such as endothelial disease and hormonal disorder cause the development of erectile dysfunction (ED). However, the relationship between vitamin D deficiency (VDD) and ED is unclear. Moreover, the benefit of vitamin D replacement on ED patients with VDD is uncertain. As far as we know, there is no study yet in the literature regarding the addition of vitamin D to phosphodiesterase type 5 inhibitors in the treatment of ED patients with VDD. In this study, we investigated whether adding vitamin D to daily tadalafil treatment would be beneficial in ED patients with VDD., Methods: A total of 111 patients with VDD accompanying ED were retrospectively evaluated between January 2016 and December 2019. Patients were divided into 2 groups according to the treatment they received. Group 1 (n = 58) was treated with daily oral tadalafil 5 mg, while group 2 (n = 53) received oral tadalafil 5 mg and 4,000 IU vitamin D3. Total International Index of Erectile Function-15 (IIEF-15) scores and vitamin D levels of the groups were compared at the end of the study., Results: The mean vitamin D level was increased statistically significant in group 2, but no difference was seen in group 1 (p < 0.001 and p > 0.05, respectively). There was a significant increase in median erectile function, orgasmic function, sexual desire, sexual satisfaction, and overall satisfaction scores in both groups (p < 0.001). However, the increase in median erectile function and sexual desire scores was significantly higher in group 2 compared to group 1 at the end of the study (p = 0.01 and p < 0.001, respectively)., Conclusion: We found that adding vitamin D to 5 mg oral daily tadalafil treatment may have an additional positive effect on erectile function and sexual desire in ED patients with VDD., (© 2021 S. Karger AG, Basel.)

The treatment of impotence is mainly centered on the liver and kidney, but it is also closely related to the spleen and stomach. Spleen and stomach are the "acquired foundation", "the source of qi and blood biochemistry" and "the hub of qi rise and fall", which are of great significance to ensure the normal erectile function. The spleen and stomach is closely related to the liver and kidney, and the rise and fall of the spleen and stomach function can affect the erectile function indirectly through the two organs. At present, in clinical and scientific research, remarkable progress has been made in the treatment of impotence from the spleen and stomach. This paper intends to summarize the progress in the treatment of impotence based on the theory of spleen and stomach through the collation of literature.

Erectile dysfunction (ED) is portrayed as lasting deficiency to achieve or sustain penile erection in successful vaginal penetration and is a major problem affecting the quality of life in men. The number of ED sufferers worldwide is anticipated to reach 322 million, by 2025. In recent years, many publications and studies have been made in the field of ED. Our aim was to perform a detailed bibliometric analysis of erectile dysfunction literature. In this study, we downloaded the data of the publications from the Web of Science Core Collection. All items indexed in these databases between 1975 and 2018 were included. Documents produced in 2019 were excluded. We searched in WoS databases for the keywords of 'erectile dysfunction' and 'impotence'. Our basic search into WoS databases retrieved a total of 28,266 documents indexed between 1975 and 2018. English dominated impotence literature (92.541%) followed by German, French and Korean (2.136%, 1.920% and 1.180% respectively). The United States has made tremendous improvement in ED studies and is still the effective country. The most prolific author was Montorsi F with 330 articles from Italy, and three-fifth of the authors were from the USA., (© 2020 Blackwell Verlag GmbH.)

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.

Background: Metabolic syndrome (MetS) has a negative impact on functional recovery and complications after many surgical procedures., Aim: To assess the role of Mets on functional outcomes and complications after radical prostatectomy (RP) for prostate cancer., Patients and Methods: Complete data were collected from 5758 patients, undergoing RP at a single referral centers in a 10-year period and the presence of MetS before surgery was ascertained in 17.7% of them using a modified version of the IDF-AHA/NHLBI criteria. Outcomes included 1-year continence and potency rates, early (≤90 days) and late (>90 days) complications., Results: Postoperative continence (no pads) was significantly less likely in MetS patients (75.4% vs 82.6%, P < .01), despite no difference in preoperative continence. Erections with or without therapy were reached in 55.8% of non-MetS and 41.8% of MetS patients (P < .01), in this case a significant difference in preoperative function was seen. No differences in early and late complications, except for wound infections (5.8% vs 3.9%, P < .01) were observed., Conclusions: In the present study RP was safe from the complications standpoint in MetS patients, but the presence of the syndrome was a significant risk factor for post-RP incontinence and impotence., (© 2019 Wiley Periodicals, Inc.)

Introduction: Erectile dysfunction (ED) is a major health care problem that has implications for quality of life., Aim: This umbrella review sought to synthesize all meta-analytic research on risk factors, treatment, and prevalence of ED., Methods: 8 electronic databases were searched for relevant meta-analyses in June 2018. The evidence was graded with 2 measures that use quantitative criteria to establish the quality of report writing and confidence in the effect size reported., Main Outcome Measures: Lifestyle factors, genetic markers, medical conditions, treatments., Results: In total, 98 meta-analyses were identified that included 421 meta-analytic effects, 4,188 primary-effects, and 3,971,122 participants. Pooled estimates showed that an unhealthy lifestyle, genetic markers, and medical conditions were associated with an increased risk of ED. Testosterone therapy and phosphodiesterase type 5 inhibitors showed the greatest treatment efficacy, with mild adverse events observed across treatments. Psychological and behavior change interventions produced effect sizes that were comparable to medication but had greater imprecision in effect sizes. There was little evidence that combined treatments were more efficacious than single treatments. Meta-analyses of prevalence estimates showed consistent age trends but were limited to particular regions or clinical samples, meaning that global estimates of ED are difficult to determine., Clinical Implications: The umbrella review synthesized findings for many treatment options that might aid evidence-based clinical decision-making. Based on prevalence estimates, we recommend that primary care physicians take a proactive approach and enquire about erectile problems in all men over age 40 displaying any health-related issue (eg, overweight, cigarette smoking)., Strengths & Limitations: Strengths include the calculation and comparison of summary estimates across multiple meta-analyses. Limitations include heterogeneity in research quality across research themes limiting effect size comparisons., Conclusion: The review provides summary estimates for 37 risk factors and 28 treatments. Meta-analyses of risk factors often did not control for important confounders, and meta-analyses of randomized trials were not exclusive to double-blinded trials, active placebo controls, or tests of long-term effects. We recommend further meta-analyses that eliminate lower quality studies and further primary research on behavioral and combined treatments. Allen MS, Walter EE. Erectile Dysfunction: An Umbrella Review of Meta-Analyses of Risk-Factors, Treatment, and Prevalence Outcomes. J Sex Med 2019;16:531-541., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The prevalence of erectile dysfunction (ED) is substantial and continues to rise. Current therapeutics for ED consist of oral medications, intracavernosal injections, vacuum erection devices, and penile implants. While such options may manage the disease state, none of these modalities, however, restore function. Stem cell therapy has been evaluated for erectile restoration in animal models. These cells have been derived from multiple tissues, have varied potential, and may function via local engraftment or paracrine signaling. Bone marrow-derived stem cells (BMSC) and adipose-derived stem cells (ASC) have both been used in these models with noteworthy effects., Aim: Herein, we will review the pathophysiology of ED, animal models, current and novel stem-cell based therapeutics, clinical trials and areas for future research., Methods: The relevant literature and contemporary data using keywords, "stem cells and erectile dysfunction" was reviewed., Main Outcome Measure: Examination of evidence supporting the association between erectile dysfunction and adipose derived stem cells, bone marrow derived stem cells, placental stem cells, urine stem cells and stem cell therapy respectively., Results: Placental-derived stem cells and urine-derived stem cells possess many similar properties as BMSC and ASC, but the methods of acquisition are favorable. Human clinical trials have already demonstrated successful use of stem cells for improvement of erectile function., Conclusion: The future of stem cell research is constantly being evaluated, although, the evidence suggests a place for stem cells in erectile dysfunction therapeutics. Matz EL, Terlecki R, Zhang Y, et al. Stem Cell Therapy for Erectile Dysfunction. Sex Med Rev 2019;7:321-328., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Erectile dysfunction (ED) is a common medical condition that requires high-quality evidence to guide clinical practice; however, systematic reviews (SRs) and meta-analyses (MAs) often vary in quality, raising concerns regarding the validity of their results., Aim: To perform an objective analysis of SRs and MAs in ED treatment and management and to report on the quality of published literature., Methods: A comprehensive search in PubMed/MEDLINE and EMBASE of 12 high-impact urology journals was used to identify relevant publications. 2 authors independently performed searches, screened citations for eligibility, extracted data for analysis, and graded methodologic quality using A Measurement Tool to Assess Systematic Reviews (AMSTAR) criteria., Main Outcome Measures: The main outcome was AMSTAR score, which is a validated tool to evaluate the quality of SRs and MAs., Results: 31 publications met inclusion criteria and were included in the analysis. The mean AMSTAR score (± SD) among all publications was 6.5 (±2.2) of 11, reflecting "fair to good" quality. 74.2% of systematic reviews and meta-analyses focused on pharmaceutical therapy for ED, with 51.6% studying the effect of phosphodiesterase-5 inhibitors. Only 1 SR/MA studied intracavernosal injection therapy and vacuum erection devices. No publications studied intraurethral injection therapy or implantable penile prostheses. Although not statistically significant, there has been a trend of increasing quality of SRs/MAs over time (P = .072)., Clinical Implication: The methodologic quality of SRs/MAs should be assessed to ensure high-quality evidence for clinical practice guidelines in ED treatment and management., Strength & Limitation: The data showed that methodologic quality of SRs/MAs in the treatment and management of ED is increasing over time. 12 high-impact urology journals were included in our search, which may introduce selection bias in our results., Conclusions: This review highlights a need for increased effort to study second- and third-line treatments for patients who fail oral therapy. Greenberg DR, Richardson MT, Tijerina JD, et al. The Quality of Systematic Reviews and Meta-Analyses in Erectile Dysfunction Treatment and Management Published in the Sexual Medicine Literature. J Sex Med 2019;16:394-401., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Aim To investigate etiological link between acute myocardial infarction (AMI) and the accompanying impotence/erectile dysfunction (ED). Methods Study included 99 male patients (48 who had AMI - patient group, and 51 healthy examinees without previous cardiovascular disease - control group). All patients completed a standardized questionnaire, the International Index of Erectile Function (IIEF-5). Results Older patients had significantly lower IIEF-5 score (negative correlation) (p<0.05), but higher ED degree (significant positive correlation) (rho=0.522; p=0.0001). In the patient group, 37 (77.1%) patients had ED, while in the control group it was found in 26 (51%) examinees (p<0.05). A clear correlation was found between incidence of ED and diabetes, dyslipidaemia, hypertension and positive family history (they were more common in patients with ED, with no statistically significant difference). There was no statistically significant difference between patients with ED and patients without ED according to the beta-blocker usage (p=0.824): ED was reported in 11 (68%) patients in the group who used carvedilol, 14 (82.3%) in the group who used metoprolol, and nine (81.8%) who used nebivolol. Conclusion Myocardial infarction as well as age are directly related to the occurrence of ED. Cardiovascular risk factors are in direct correlation for the occurrence of erectile dysfunction after myocardial infarction., (Copyright© by the Medical Assotiation of Zenica-Doboj Canton.)

Erectile dysfunction (ED) is a common condition affecting more than 20% of men over 60 years, yet little is known about its genetic architecture. We performed a genome-wide association study of ED in 6,175 case subjects among 223,805 European men and identified one locus at 6q16.3 (lead variant rs57989773, OR 1.20 per C-allele; p = 5.71 × 10 -14 ), located between MCHR2 and SIM1. In silico analysis suggests SIM1 to confer ED risk through hypothalamic dysregulation. Mendelian randomization provides evidence that genetic risk of type 2 diabetes mellitus is a cause of ED (OR 1.11 per 1-log unit higher risk of type 2 diabetes). These findings provide insights into the biological underpinnings and the causes of ED and may help prioritize the development of future therapies for this common disorder., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The serendipitous discovery of sildenafil (Viagra [sildenafil citrate]) as a treatment for erectile dysfunction (ED) is one of the most fascinating drug development stories of our time. When sildenafil was approved by the U.S. Food and Drug Administration in 1998, it revolutionized the treatment protocol for men with ED, once considered a psychological issue or an inevitable part of aging., Aim: To review the discovery of sildenafil and its role in changing the field of sexual medicine in the context of the epidemiology and history of treatment for ED., Methods: For this narrative review, a literature search was conducted to identify essential articles and was supplemented by author observations from a historical perspective., Main Outcome Measure: A broad overview of ED and its past, current, and future treatments., Results: ED is a prevalent condition for which medical treatment had been limited to genitally localized interventions, including surgery, vacuum pumps, injectable therapies, and intraurethral suppositories. The discovery of sildenafil provided a safe, oral pharmacotherapy for the treatment of ED, sparking greater understanding of the science behind ED and its role in men's overall health., Conclusion: The approval of sildenafil initiated a global conversation about ED that had profound implications for patients, methods of clinical practice, and academic sexual medicine. These changes will catalyze continued advances in ED treatment. Goldstein I, Burnett AL, Rosen RC, et al. The serendipitous story of sildenafil: an unexpected oral therapy for erectile dysfunction. Sex Med Rev 2019;7:115-128., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Enhanced external counterpulsation (EECP) is a noninvasive treatment option widely applied in patients with erectile dysfunction (ED). The aim of this study is to review the efficacy of EECP in patients suffering from ED., Methods: PubMed, MEDLINE, Google Scholar, Tripdatabase, Scopus, and Cochrane library databases were searched for articles with the following search terms: enhanced external counterpulsation and erectile dysfunction. No restrictions with respect to study setting, date of publication, and language were imposed., Results: From an initial set of 208 records, 4 studies were selected after a final review. A total of 177 patients with a mean age of 59.98 years were included in these studies, with 20-35 hours per week of EECP treatment. Three studies used the International Index of Erectile Function questionnaire and one applied a four-item questionnaire and a peak systolic flow measurement. All of these parameters were significantly improved after the EECP treatment., Conclusion: To the best of our knowledge, this is the first study reviewing the clinical effectiveness of EECP in patients with ED. According to the articles reviewed in this study, an improvement in erectile function after EECP treatment courses has been observed in patients with and without coronary artery disease without any significant adverse effects., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Variability in prices of medications is a well-known phenomenon; however, this variability has not been quantified in the realm of erectile dysfunction (ED) medications. ED medications are ideal for this quantification, because they are often not covered by insurances; therefore, the cost is the most direct reflection of price variability among pharmacies as they affect the patients., Aim: To evaluate the variability in cash prices for phosphodiesterase type 5 inhibitors (PDEIs) for ED. We also evaluated whether certain types of pharmacies consistently offer better pricing than others, and whether there was any correlation with demographic factors., Methods: 331 pharmacies were contacted within a 25-mile radius of our institution to obtain the cash price for 4 commonly used ED medications with prespecified doses. After exclusion, 323 pharmacies were categorized as chain, independent, wholesale, or hospital-associated. Cash prices for the specified medications were evaluated. In addition, we identified demographic and socioeconomic factors to determine if these had an impact on median drug pricing within each zip code., Main Outcome Measure: The main outcome was the cost for patients to fill each prescription., Results: Independent pharmacies provided the lowest cost for 3 of 4 of the PDEIs. The largest price difference for 10 tablets of 100 mg sildenafil between all pharmacies was 38,000%. The median cost difference between independent pharmacies and chain pharmacies for sildenafil was >900%, and >1,100% for independent pharmacies vs hospital-associated pharmacies. Demographic and socioeconomic factors had no impact on the cost., Clinical Implications: Our goal is to promote patient counseling among practitioners and to empower patients to shop for the best prices for their medications., Strength and Limitations: A strength of the study is the large cohort that was surveyed; however, a weakness is that the large majority of the cohort was comprised of chain pharmacies. Mail pharmacies could not be evaluated as they required a valid prescription before offering prices., Conclusion: The drastic differences in cash prices for the PDEIs give us an insight into the variability and cost-inflation of medications in the United States. These patterns hold true for other essential medications as well, and improved transparency will allow patients to make informed decisions when choosing where to purchase their medications. It may also encourage certain pharmacies to provide medications at more affordable prices. Mishra K, Bukavina L, Mahran A, et al. Variability in prices for erectile dysfunction medications-Are all pharmacies the same? J Sex Med 2018;15:1785-1791., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The 3-piece inflatable penile prosthesis (IPP) is the gold standard treatment for male erectile dysfunction when other less invasive approaches are contra-indicated or unacceptable for the patient. There are currently 2 surgical approaches for IPP implantation: the penoscrotal (PS) and the infrapubic (IP) incision., Aim: To assess the most recent evidence on the impact of surgical approach for 3-piece IPP implantation in patients with erectile dysfunction., Methods: A systematic literature review was performed using the MEDLINE (PubMed) and Cochrane Libraries databases in November 2017 to identify all studies investigating 3-piece IPP with a specified surgical access., Outcomes: The following key words were used in combination: "infrapubic," "transcrotal," "penoscrotal," "peno-scrotal," and "penile prosthesis." Additional references were obtained from the reference lists of full-text manuscripts. We used a narrative synthesis for the analyses of the studies., Results: 22 Studies reporting data on 3-piece IPP implantation with a specified surgical approach were found in the literature. While IPPs are most commonly positioned through a PS incision, the IP approach is a faster procedure. No cases of glans hypoesthesia after IPP placement with an IP approach were reported, and the overall peri-prosthetic infection rate was 3.3% or less. Patient satisfaction rates were higher than 80% in both groups., Conclusions: Both the IP and PS approaches are viable and effective strategies for a 3-piece IPP placement, and result in high satisfaction rates. To date there is no evidence that an incision strategy may reduce infection rates. Penile sensory loss following an IP approach remains a virtual risk. It is recommended that the surgeon executing the implant have knowledge of both accesses and be capable of tailoring the incision strategy for complex cases. The chosen method should be based on the patient's specific anatomy, surgical history, and surgeon experience. Palmisano F, Boeri L, Cristini C, et al. Comparison of Infrapubic vs Penoscrotal Approaches for 3-Piece Inflatable Penile Prosthesis Placement: Do We Have a Winner? Sex Med Rev 2018;6:631-639., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Papaverine hydrochloride (PaHCl) is an old, well-known drug with spasmolytic activity but it has therapeutic effect in erectile dysfunction, too. As an intracavernous injection, it is not used in urologic clinics today because the side effects of the injection are pain, scarring or priapism. Our aim was to develop and test a topical semi-solid preparation containing PaHCl that would provide an alternative administration option by eliminating the undesirable side effects of the injection., Materials and Methods: Lyotropic liquid crystal (LLC) systems were formulated as a semi-solid preparation with different concentrations of PaHCl. The characterization of the LLC structure was performed by polarization microscopy using a Leica image analyzer and rheological measurements. The drug diffusion and penetration tests were performed with in vitro synthetic membrane and an ex vivo human epidermis, using Franz diffusion cell to test the skin penetration of PaHCl. Human skin was investigated by Raman microscope to visualize the Active Pharmaceutical Ingredient (API) in different skin layers., Results: The results of diffusion and penetration showed reverse concentration dependency. The in vitro and ex vivo studies correlated with each other and the results of Raman microscopy. The LLC structure influenced the penetration results, the lower viscosity and lamellar structure increased penetration through the skin., Conclusion: Based on our results, a PaHCl containing topically used LLC formulation may be a suitable and effective alternative to the injectable formulation., Competing Interests: Disclosure The author reports no conflicts of interest in this work.

Objective: To investigate the pooled incidence or the prevalence of erectile dysfunction, and to assess the risk of erectile dysfunction in patients with atrial fibrillation., Methods: A systematic review was carried out in the MEDLINE, EMBASE and Cochrane databases from inception through January 2018 to identify: (i) studies that reported the incidence and/or prevalence of erectile dysfunction in atrial fibrillation patients; or (ii) studies that assessed the association between atrial fibrillation and erectile dysfunction. Pooled odds ratios and 95% confidence intervals were calculated using a random effects model., Results: Five observational studies (27 841 patients) were enrolled. The pooled estimated prevalence of erectile dysfunction in atrial fibrillation patients was 57% (95% confidence interval 50-64, I 2  = 0). A study showed an incidence of newly diagnosed erectile dysfunction in atrial fibrillation patients of 0.96% during the mean follow-up duration of 4.67 ± 3.20 years. There was a significant association of atrial fibrillation with an increased risk of erectile dysfunction, with a pooled odds ratio of 1.79 (95% confidence interval 1.44-2.23, I 2  = 0%). The data on the risk of atrial fibrillation development in patients with erectile dysfunction were limited. A study showed the comparable risk of atrial fibrillation in patients with erectile dysfunction (odds ratio 1.03, 95% confidence interval 0.67-1.5), when compared with those without erectile dysfunction., Conclusions: The present study suggests a significant association between erectile dysfunction and atrial fibrillation. The overall estimated prevalence of erectile dysfunction among atrial fibrillation patients is 57%. However, despite limited data, the current evidence suggests a low incidence of new erectile dysfunction in atrial fibrillation patients., (© 2018 The Japanese Urological Association.)

Objective: The aim of the study is the evaluation of the efficacy and safety of the treatment with topical alprostadil (Vitaros © ) in post-robot assisted radical prostatectomy (RARP) rehabilitation therapy of patients with erectile dysfunction (ED)., Methods: Seventy-four patients were enrolled and underwent non-nerve-sparing RARP., Inclusion Criteria: age <75, preoperatively International Index of Erectile Function (IIEF-5) >16, erection hardness score (EHS) ⩾2, weekly sexual intercourse ⩾1, affirmative answers to Sexual Encounter Profile Question (SEP-Q) 2 and SEP-Q3, Charlson Comorbidity Index (CCI) ⩽5, Eastern Cooperative Oncology Group (ECOG) performance status ⩽1, no moderate/severe cardiovascular disease., Results: Vitaros was administered ⩾2 twice a week. At month 6, the IIEF-5 decreased from 20.5 preoperative to 18.1 post-treatment. EHS score decreased from a mean of 3.3 to a mean of 3.0. The quality of life score decreased from an average of 5.1 to 2.3. Weekly sexual intercourse decreased from an average of 2.1 to 1.7. Six patients dropped out; 89.7% patients showed a positive SEP-Q2 and 77.8% a positive SEP-Q3. All patients responded positively to Global Assessment Questions (GAQ)-1 and 97% to GAQ-2. Of all 68 analyzed patients, 13 (17.6%) switched to intracavernous injection therapy., Conclusions: In conclusion, Vitaros may become a viable alternative to common injective therapies in well-selected patients after RARP.

Purpose: The pelvic floor is now well known and its role in the mechanism of erection is demonstrated. We wanted to know what is the evidence of the effectiveness of perineal rehabilitation in erectile dysfunction., Materials: An English search was performed in Google scholar and databases PubMed, Medline, Pedro with the keywords "pelvic floor, erectile dysfunction, impotence, physiotherapy, exercises, rehabilitation, PFMT". We have selected randomized clinical trials published in indexed journals., Results: Six randomized trials were selected. Five of them have shown statistically and clinically significant effectiveness in populations of men with erectile dysfunction and various underlying pathologies. In the fifth trial, the difference in effectiveness was not statistically significant. At 3 months, the best-conducted study showed an average improvement of 7 points at IIEF-5 compared to the control group (P-value: 0.004). Rehabilitation has not resulted in any adverse side effects. However, these studies were conducted in heterogeneous populations and the protocols for pelvic floor muscle strengthening rehabilitation differed from one study to another, making it impossible to formulate a specific recommendation for clinical practice., Conclusion: Based on the results of this literature review, perineal physiotherapy may have a role to play in the management of erectile dysfunction., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: A new oro-dispersible film (ODF) formulation of sildenafil has been developed for the treatment of erectile dysfunction (ED) to overcome the drawbacks that some patients experience when taking the conventional film-coated tablet (FCT)., Aim: To assess the effectiveness and safety of sildenafil ODF formulation in patients with ED who were using the conventional FCT., Methods: From May 2017 through July 2017, 139 patients with ED were enrolled. Data from penile color-duplex ultrasound, medical history, hormonal evaluation, and patient self-administered questionnaires were collected. All patients were administered sildenafil 100-mg FCT for 4 weeks. Thereafter, they underwent a 2-week washout period and subsequently took sildenafil 75-mg ODF for 4 weeks., Outcomes: The International Index of Erectile Function (IIEF-15), Hospital Anxiety and Depression Scale (HADS), Patient Global Impressions of Improvement (PGI-I), and Clinician Global Impressions of Improvement (CGI-I) questionnaires were administered and severity of ED was classified as severe (IIEF-15 score ≤ 10), moderate (IIEF-15 score 11-16), or mild (IIEF-15 score = 17-25)., Results: All patients completed the final protocol. Differences in mean IIEF scores for erectile function, orgasmic function, sexual desire, and intercourse satisfaction were significantly in favor of sildenafil 100-mg FCT, whereas the mean score for overall satisfaction was in favor of sildenafil 75-mg ODF. A significant difference in changes in HADS score was found from washout to final follow-up (mean difference = -0.19; P < .01). For the ODF formulation, the median CGI-I score was 3.5 (interquartile range [IQR] = 2.5-4.5) and the median PGI-I score was 3.0 (IQR = 2.0-4.0). The median action time was 20.0 minutes (IQR = 15.0-30.0) and the median mouth time was 60.0 seconds (IQR = 30.0-120.0)., Clinical Implications: The ODF formulation of a widely known drug, with the same safety and effectiveness of the FCT, was better appreciated by patients in overall satisfaction., Strengths and Limitations: This is the first clinical trial to assess the efficacy of a new formulation of sildenafil in patients with ED. The limitations of the study are related to the methodology used: it was not a case-control study and the patients were not drug-naïve for ED treatment. Therefore, only the "additional" side effects of the ODF formulation compared with FCT are reported., Conclusion: The new ODF formulation is as efficient and safe as the FCT formulation and offers a new choice of treatment to specialists for more precisely tailored therapy. Cocci A, Capece M, Cito G, et al. Effectiveness and Safety of Oro-Dispersible Sildenafil in a New Film Formulation for the Treatment of Erectile Dysfunction: Comparison Between Sildenafil 100-mg Film-Coated Tablet and 75-mg Oro-Dispersible Film. J Sex Med 2017;14:1606-1611., (Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Urinary incontinence (UI) and erectile dysfunction (ED) remain the most common long-term complications of prostatectomy, with a significant impact on sexual health and quality of life., Aims: To determine the relation between UI and moderate to severe ED and the risk factors for UI in patients undergoing robotic-assisted laparoscopic prostatectomy., Methods: Patients in our institutional database who underwent robotic-assisted laparoscopic prostatectomy for prostate cancer (2006-2013) and who completed the University of California-Los Angeles Prostate Cancer Index and the Sexual Health Inventory for Men (SHIM) surveys at 12 months after prostatectomy were eligible for inclusion. Men who reported use of no urinary pads per day were considered continent, whereas men who used at least one pad per day were considered incontinent. Men with moderate to severe ED based on a SHIM score no higher than 11 were considered to have ED. Patients who had preoperative moderate to severe ED and/or UI based on these definitions were excluded from further analysis., Outcomes: A better understanding of what increases the risk for UI after a prostatectomy and how it can co-occur with ED., Results: We analyzed 464 patients who met the inclusion criteria. After prostatectomy, 36% of patients had UI and 47% of patients had moderate to severe ED. Of all patients with ED, 45% (98 of 216) were incontinent compared with 27% (67 of 248) of patients without ED (P < .001). On multivariable analysis, older age at diagnosis (odds ratio [OR] = 1.05, P = .002) and ED (OR = 1.88, P = .005) were independent predictors for incontinence. The use of unilateral nerve sparing (OR = 1.03, P = .94) or no nerve sparing (OR = 0.53, P = .50) during surgery did not have an impact on postoperative incontinence., Clinical Implications: Understanding that ED is an independent predictor of UI after robotic-assisted laparoscopic prostatectomy has important clinical implications and suggests a common anatomic pathway., Strengths and Limitations: Our focus on different measurements of incontinence and their relation to ED and our use of validated questionnaires to define incontinence and ED were important strengths of this study. Limitations of our study include its retrospective nature and the fact that our results were drawn from a single-center database of a tertiary referral hospital., Conclusion: Our results show that the presence of moderate to severe ED after prostatectomy is an independent risk factor for incontinence, suggesting a possible common pathway for these two complications. Further studies to investigate the anatomic and clinical bases of this relation are warranted. Tsikis ST, Nottingham CU, Faris SF. The Relationship Between Incontinence and Erectile Dysfunction After Robotic Prostatectomy: Are They Mutually Exclusive? J Sex Med 2017;14:1241-1247., (Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Vesicular drug delivery systems have recently gained attention as a way of improving dosing accuracy for drugs with poor transdermal permeation. The current study focuses on utilization of the natural biocompatible vesicles to formulate vardenafil nanoethosomes (VRD-NE), for the enhancement of their transdermal permeation and bioavailability. Fifteen formulations were prepared by thin-layer evaporation technique according to Box-Behnken design to optimize formulation variables. The effects of lipid composition, sonication time, and ethanol concentration on particle size and encapsulation efficiency were studied. The diffusion of vardenafil (VRD) from the prepared nanoethosomes specified by the design was carried out using automated Franz diffusion cell apparatus. The optimized formula was investigated for in vivo pharmacokinetic parameters compared with oral VRD suspension. Confocal laser scanning microscopy images were used to confirm enhanced diffusion release of VRD in rat skin. The results showed that the optimized formula produced nanoethosomes with an average size of 128 nm and an entrapment efficiency of 76.23%. VRD-NE provided a significant improvement in permeation with an enhancement ratio of 3.05-fold for a film made with optimally formulated VRD-NE compared with a film made with VRD powder. The transdermal bioavailability of VRD from the nanoethosome film was approximately twofold higher than the oral bioavailability from an aqueous suspension. VRD-NE thus provide a promising transdermal drug delivery system. As a result, management of impotence for a longer duration could be achieved with a reduced dosage rate that improves patient tolerability and compliance for the treatment of erectile dysfunction.

The traditional inflatable penile prosthesis (IPP) reservoir placement is below the transversalis fascia in the space of Retzius. In 2002, Dr. Steve Wilson described ectopic reservoir placement, thereby providing a safe and effective alternative for implant surgeons. This new approach obviated the need for a second incision and decreased operative times during surgery. In the manuscript, he also described the introduction of a reservoir lock-out valve, which prevents autoinflation of the penile implant. The development of lockout valves and flat reservoirs has contributed to the early success and feasibility of submuscular placement techniques. Thirteen years after Dr. Wilson's pivotal study, this technique should be in the armamentarium of all urologic prosthetic surgeons. Accordingly, in certain subsets of patients, ectopic/ submuscular reservoir site placement should be considered a safe, effective alternative to standard reservoir placement in the space of Retzius., (© 2015 International Society for Sexual Medicine.)

Introduction: There is growing interest in using exercise to treat. Although many studies have highlighted the relationship between better erectile function and exercise, black men have been underrepresented in the literature., Aims: This study aims to determine whether or not exercise is associated with better erectile as well as sexual function in black men and define a minimum exercise threshold for which better erectile/sexual function is seen in a cross-sectional study., Methods: Our study population consisted of 295 healthy controls from a case-control study assessing risk factors for prostate cancer conducted at the Durham Veterans Affairs Medical Center, which contained a substantial proportion of black men (n = 93; 32%). Exercise and erectile/sexual function were both determined from self-reported questionnaires. Subjects were stratified into four exercise groups: <3 (sedentary), 3-8.9 (mildly active), 9-17.9 (moderately active), and ≥18 (highly active) metabolic equivalents (MET) hours/week. The association between exercise and erectile/sexual function was addressed utilizing multivariable linear regression analyses., Main Outcome Measures: Erectile/sexual function was defined by the validated Expanded Prostate Cancer Index Composite sexual assessment, which was analyzed as a continuous variable (sexual function score). Clinically significant better function was defined as half a standard deviation (SD) (16.5 points)., Results: Median sexual function score was 53 (SD = 33). Higher exercise was associated with a better sexual function score (P < 0.001). Importantly, there was no interaction between black race and exercise (P-interaction = 0.772), meaning more exercise was linked with better erectile/sexual function regardless of race. Overall, exercise ≥18 MET hours/week predicted better erectile/sexual function (P < 0.001) with a clinically significant 17.3-point higher function. Exercise at lower levels was not statistically (P > 0.147) or clinically (≤8.14 points higher function) associated with erectile/sexual function., Conclusions: In a racially diverse population, exercise ≥18 MET hours/week is highly associated with better erectile/sexual function regardless of race., (© 2015 International Society for Sexual Medicine.)

Erectile function recovery after radical prostatectomy (RP) is an increasingly prominent quality-of-life outcome following surgery. Following RP many men, despite the advent of cavernous nerve-sparing surgical technique, have moderately or significantly impaired erectile function (EF). The term penile rehabilitation (PR) is used to define interventions that maintain the health of erectile tissue in the context of nervous, vascular, and structural tissue injury. The goal of PR is to regain, as closely re-approximate, preoperative erectile function. PR is based on an increasing volume of preclinical and clinical data, but conclusive evidence of efficacy has not been established, and therefore the concept of PR remains controversial. The optimal PR regimen has not been established, but all strategies rely on one or more erectile dysfunction treatments to be administered on a regular basis regardless of actual use for sexual activity. This review highlights recent studies and evidence related to PR., (© The Author(s) 2014.)

Introduction: Erectile dysfunction (ED) is an increasing health problem that demands effective treatment. There is evidence that phosphodiesterase-5 inhibitors (PDE5-Is) and psychological intervention (PI) are effective treatment options; however, little is known about their comparative efficacy and the efficacy of combined treatments., Aim: The aim of this systematic review and meta-analysis is to evaluate the comparative efficacy of PI, PDE5-Is, and their combination in the treatment of ED., Main Outcome Measures: Primary outcome was ED symptoms, and secondary outcome was sexual satisfaction of the patient., Methods: A systematic literature search was conducted in order to identify relevant articles published between 1998 and 2012. We included randomized controlled trials and controlled trials comparing PI with PDE5-I treatment or one of them against a combination of both., Results: Eight studies with a total number of 562 patients were included in the meta-analysis. The results of the included studies are inconclusive, though they show a trend towards a larger effect of combined treatment compared with PI or PDE5-I treatment alone. The meta-analysis found that, overall, combined treatment was more efficacious for ED symptoms than PDE5-I treatment or PI alone. Combined treatment was more efficacious than PDE5-I use alone on sexual satisfaction. No differences were found between PDE5-Is and PI as stand-alone treatments. None of the moderators (treatment duration, methodological quality, or researcher allegiance) altered the effects., Conclusions: The combination of PI and PDE5-Is is a promising strategy for a favorable outcome in ED and can be considered as a first-choice option for ED patients. Stronger RCTs are required to confirm this initial finding., (© 2014 International Society for Sexual Medicine.)

This study compared demographic characteristics and prevalence of cardiovascular comorbidities between men with mild erectile dysfunction (ED) and men with more severe ED. Men with 6-month history of ED and in monogamous heterosexual relationships were included. Non-responders to type 5 phosphodiesterase inhibitors or patients receiving regular treatment with nitrate, anticoagulants, androgens, and anti-androgens were excluded. ED was defined according to the International Index of Erectile Function questionnaire score: no ED (≥26), mild ED (22-25), and others (<22). The review identified 70 patients with mild ED (6.0%, group A) and 1098 patients with more severe ED (94.0%, group B) were included. Of the patients in group B, 365 had mild-to-moderate ED (30.5%), 505 had moderate ED (43.2%), and 233 had severe ED (20.0%). Mean ages and body mass indices showed no differences between groups A and B. Group A had shorter mean duration of ED (p = 0.025). Although patients in group A had milder ED with shorter duration than group B patients, cardiovascular risk factors such as diabetes, hypertension and lipid disorder were still common for group A. The most common comorbidity was diabetes, which was twice as likely for patients in group B. Except for diabetes the prevalence of all diseases was comparable between the two groups. In conclusion, patients with mild ED should be closely evaluated for cardiovascular comorbidities.

Objectives: To evaluate the possible effects of Tribulus terrestris herbal medicine in the erectile dysfunction treatment and to quantify its potential impact on serum testosterone levels., Design and Methods: Prospective, randomized, double-blind and placebo-controlled study including thirty healthy men selected from 100 patients who presented themselves spontaneously complaining of erectile dysfunction, ≥ 40 years of age, nonsmokers, not undergoing treatment for prostate cancer or erectile dysfunction, no dyslipidemia, no phosphodiesterase inhibitor use, no hormonal manipulation and, if present hypertension and/or diabetes mellitus should be controlled. International Index of Erectile Function (IIEF-5) and serum testosterone were obtained before randomization and after 30 days of study. Patients were randomized into two groups of fifteen subjects each. The study group received 800 mg of Tribulus terrestris, divided into two doses per day for thirty days and the control group received placebo administered in the same way., Results: The groups were statistically equivalent in all aspects evaluated. The mean (SD) age was 60 (9.4) and 62.9 (7.9), P = .36 for intervention and placebo groups, respectively. Before treatment, the intervention group showed mean IIEF-5 of 13.2 (5-21) and mean total testosterone 417.1 ng/dl (270.7-548.4 ng/dl); the placebo group showed mean IIEF-5 of 11.6 (6-21) and mean total testosterone 442.7 ng/dl (301-609.1 ng/dl). After treatment, the intervention group showed mean IIEF-5 of 15.3 (5-21) and mean total testosterone 409.3 ng/dl (216.9-760.8 ng/dl); the placebo group showed mean IIEF-5 of 13.7 (6-21) and mean total testosterone 466.3 ng/dl (264.3-934.3 ng/dl). The time factor caused statistically significant changes in both groups for IIEF-5 only (P = .0004), however, there was no difference between the two groups (P = .7914)., Conclusions: At the dose and interval studied, Tribulus terrestris was not more effective than placebo on improving symptoms of erectile dysfunction or serum total testosterone., (Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.)

Objective: To evaluate satisfaction rates and results in patients with penile prosthesis (5 PP)., Materials and Methods: From January 2000 till 2009, 50 patients with organic erectile dysfunction (ED) were implanted with hydraulics penile prosthesis by the same surgeon. Medical records were collected retrospectively. We analysed demographic characteristics, type of prosthesis used, per- and postoperative complications, prosthesis explantations and satisfaction rate measured by EDITS modified., Results: Mean age of patients was 60.2 ± 8.46 years (35-75). Thirty implanted patients (60%) were diabetics. We used a peno-scrotal incision in all patients. Three types of prosthesis were used; AMS Ambicor, AMS 700, Titan OTR. A bi-compartment and three-compartment prosthesis were implanted respectively in 24 and 26 patients. The prosthesis was retrieved in two patients secondary to a mechanical failure, in three patients for prosthesis erosion, in two patients for prosthesis infection. In four out of the seven explanted patients, a second prosthesis was implanted. The EDITS questionnary was realized by telephonic interview in 47 patients after a mean follow-up of 45 months (5-114). The response rate was of 83%. The satisfaction rate was of 81%., Conclusion: In our series, the satisfaction rate was better for the three-compartment prosthesis. After 45 months of follow-up, 73% (31/42) of patients had a functional prosthesis. The non-satisfaction most frequently found were patients who have complications as sepsis; mechanical failure, and prosthesis erosion, and subjective feeling of penile length reduction., (Copyright © 2013. Published by Elsevier Masson SAS.)