Erectile Dysfunction Use Research Articles

A comprehensive history of injection therapy for erectile dysfunction, 1982-2023.

Although oral phosphodiesterase 5 inhibitors represent a first choice and long-term option for about half of all patients with erectile dysfunction (ED), self-injection therapy with vasoactive drugs remains a viable alternative for all those who are not reacting or cannot tolerate oral drug therapy. This current injection therapy has an interesting history beginning in 1982. To provide a comprehensive history of self-injection therapy from the very beginnings in 1982 by contemporary witnesses and some members of the International Society for Sexual Medicine's History Committee, a complete history of injection therapy is prepared from eyewitness accounts and review of the published literature on the subject, as well as an update of the current status of self-injection therapy. Published data on injection therapy, as a diagnostic and therapeutic tool for ED, were reviewed thoroughly by PubMed and Medline research from 1982 until June 2023. Early pioneers and witnesses added firsthand details to this historical review. Therapeutic reports of injection therapy were reviewed, and results of side effects and complications were thoroughly reviewed. The pioneers of the first hours were Ronal Virag (1982) for papaverine, Giles Brindley (1983) for cavernosal alpha-blockade (phentolamine and phenoxybenzamine), Adrian Zorgniotti (1985) for papaverine/phentolamine, and Ganesan Adaikan and N. Ishii (1986) for prostaglandin E1. Moxisylyte (thymoxamine) was originally marketed but later withdrawn. The most common side effect is priapism, with the greatest risk of this from papaverine, which has modified its use for therapy. Currently, prostaglandin E1 and trimixes continue to be the agents of choice for diagnostic and therapeutic use in ED. A recent agent is a mixture of a vasoactive intestinal polypeptide (aviptadil) and phentolamine. After 40years, self-injection therapy represents the medication with the highest efficacy and reliability rates and remains a viable option for many couples with ED. The history of this therapy is rich.

UPLC-Q-TOF-MS profiling of Viola stocksii Boiss. and evaluation of aphrodisiac potential and risk factors associated with erectile dysfunction

Ethnopharmacological relevanceViola stocksii Boiss. locally known as makhni or makhanr booti, is an important medicinal food plant with multiple therapeutic applications, including erectile dysfunction (ED). It is mixed with butter and used for boosting energy and sexual health in the subcontinent. Aims of the studyThis study was designed to evaluate the chemical composition, aphrodisiac potential and effect of V. stocksii on the risk factors associated with ED. MethodologyThe hydroethanolic extract of V. stocksii (HEEVS) was prepared through the microwave-assisted extraction (MAE) technique. The chemical composition was evaluated using preliminary phytochemical screening and UPLC-Q-TOF-MS analysis. Metals and minerals analysis was performed by an atomic absorption spectrophotometer. The aphrodisiac activity of HEEVS was evaluated using an in vivo aphrodisiac model established in male albino rats and the effect on various sexual parameters such as mount, intromission, ejaculation frequencies and mount, intromission, ejaculation latencies, postejaculatory interval, penile reflexes and serum hormone concentration were analyzed. The effect of HEEVS on various risk factors associated with ED, including prostate cancer (PC), bacterial infections, diabetes and obesity, was evaluated using various in vitro assays. Moreover, four compounds were selected from the UPLC-Q-TOF-MS profile and evaluated for in silico computational analysis against phosphodiesterase-5 (PDE-5) for possible interaction. FindingsThe phytochemical screening revealed the presence of various secondary metabolites in HEEVS, while 58 compounds were tentatively identified in the UPLC-Q-TOF-MS analysis. Various important minerals and metals such as zinc, calcium, cadmium and magnesium were detected in the atomic absorption spectrometry analysis. The in vivo aphrodisiac evaluation showed a significant (p < 0.05) increase in the mount, intromission and ejaculation frequencies and a decrease in the mount, intromission latencies and post-ejaculatory intervals at a dose of 300 mg/kg. A marked (p < 0.05) increase was observed in the concentration of serum testosterone and luteinizing hormones in HEEVS treated animals with a significant increase in total penile reflexes. The extract displayed significant anti-prostate cancer activity and a potential antibacterial spectrum against E. coli and S. aureus, with MIC50 values of 215.72 μg/mL and 139.05 μg/mL, respectively. Similarly, HEEVS was found active towards pancreatic lipase (67.34 ± 1.03%), α-glucosidase (3.87 ± 0.54 mmol ACAE/g d.w.) and α-amylase (6.98 ± 1.63 mmol ACAE/g d.w.). The in silico docking study presented a potential interaction between the selected compounds and residues of the active site of PDE-5. ConclusionThis report highlights the aphrodisiac potential of V. stocksii and provides experimental support for its traditional use in ED with an attenuative effect on the risk factors associated with ED. Moreover, the chemical composition displayed the presence of functional phytoconstituents and minerals in HEEVS and paves the way for the isolation of compounds with potent aphrodisiac activity.

Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants

BackgroundSexual dysfunction is a common side effect of Serotonergic antidepressants (SA) treatment, and persists in some patients despite drug discontinuation, a condition termed post-SSRI sexual dysfunction (PSSD). The risk for PSSD is unknown but is thought to be rare and difficult to assess. This study aims to estimate the risk of erectile dysfunction (ED) and PSSD in males treated with SAs.MethodsA 19-year retrospective cohort analysis was conducted using a computerized database of the largest HMO in Israel. ED was defined by phosphodiesterase-5 inhibitors prescriptions. 12,302 males aged 21–49 met the following criteria: non-smokers, no medical or psychiatric comorbidities or medications associated with ED, no alcohol or substance use. Logistic regression was used for estimation of ED risk in SA-treated subjects compared to non-SA-treated controls, assessed with and without the effects of age, body mass index (BMI), socioeconomic status (SES), depression and anxiety, yielding crude and adjusted odds ratios (cOR and aOR, respectively).ResultsSAs were associated with an increased risk for ED (cOR = 3.6, p < 0.000001, 95% CI 2.8–4.8), which remained significant after adjusting for age, SES, BMI, depression and anxiety (aOR = 3.2, p < 0.000001, 95% CI 2.3–4.4). The risk for PSSD was 1 in 216 patients (0.46%) treated with SAs. The prevalence of PSSD was 4.3 per 100,000.ConclusionsThis work offers a first assessment of the small but significant risk of irreversible ED associated with the most commonly prescribed class of antidepressants which should enhance the process of receiving adequate informed consent for therapy.

MP79-10 PHARMACOVIGILANCE ANALYSIS OF MELANOMA ADVERSE EVENTS IN MEN TREATED WITH SILDENAFIL FOR ERECTILE DYSFUNCTION

You have accessJournal of UrologyCME1 Apr 2023MP79-10 PHARMACOVIGILANCE ANALYSIS OF MELANOMA ADVERSE EVENTS IN MEN TREATED WITH SILDENAFIL FOR ERECTILE DYSFUNCTION Muhieddine Labban, Edoardo Beatrici, Dejan K. Filipas, Benjamin V. Stone, Nguyen David-Dan, Elio Adib, Kevin R Melnick, Alexander P. Cole, Stuart R. Lipsitz, Toni K. Choueiri, and Quoc-Dien Trinh Muhieddine LabbanMuhieddine Labban More articles by this author , Edoardo BeatriciEdoardo Beatrici More articles by this author , Dejan K. FilipasDejan K. Filipas More articles by this author , Benjamin V. StoneBenjamin V. Stone More articles by this author , Nguyen David-DanNguyen David-Dan More articles by this author , Elio AdibElio Adib More articles by this author , Kevin R MelnickKevin R Melnick More articles by this author , Alexander P. ColeAlexander P. Cole More articles by this author , Stuart R. LipsitzStuart R. Lipsitz More articles by this author , Toni K. ChoueiriToni K. Choueiri More articles by this author , and Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In 2016, the Food and Drug Administration issued a warning regarding a possible association between sildenafil and melanoma. Therefore, we sought to conduct a pharmacovigilance analysis to examine the association between sildenafil prescribed for erectile dysfunction and melanoma. METHODS: We collected spontaneous adverse drug reactions for men who used sildenafil for erectile dysfunction captured in VigiBase (1968-2019), the World Health Organization’s global database of individual case safety reports. Our primary endpoint was cutaneous or ocular melanoma. The disproportionality signal for melanoma with sildenafil use was reported using the reporting odds ratio (ROR), the odds of having the adverse event (melanoma) with the drug of interest (sildenafil) compared to the odds of the same event occurring with all other drugs in the database. We examined confounding by indication, dose, age at report submission, region, before and after 2014 when there was a sharp increase in awareness about the topic, another phosphodiesterase type-5 inhibitor (tadalafil), drugs prescribed for erectile dysfunction with different mechanisms of action, drugs unrelated to erectile dysfunction but prescribed among the same age group, and drugs associated with non-melanoma skin cancer. RESULTS: We identified 11,250 reports of cutaneous and/or ocular melanoma, of which 763 (6.9%) were reported with sildenafil use among men. Among men who used sildenafil, most reports were among men 45-64 years of age (21.8%), originated from the Americas (99.6%), and were reported after 2015 (99.5%). We found a significant disproportionality signal of melanoma reports with sildenafil use for erectile dysfunction (ROR 90.0, 95%CI 80.6-100.4). More reports were recorded among men ≥45 years (ROR 34.8, 95%CI 30.8-39.3) and after 2014 (ROR 98.8, 95%CI 91.0-107.2). We also found a dose-response relationship with higher doses of sildenafil (≥50 mg) being associated with melanoma (ROR 12.3, 95%CI 9.5-15.9), but not lower doses. Similar trends were found for tadalafil across confounding variables. Other drugs with different mechanisms of action used for erectile dysfunction, drugs unrelated to the condition but prescribed among the same age group, and drugs associated with non-melanoma skin cancer did not meet the threshold for significance. CONCLUSIONS: Herein, we found that sildenafil prescribed for erectile dysfunction is associated with cutaneous and ocular melanoma. Thus, our results support the need to keep sildenafil on the Food and Drug Administration’s list of drugs with potential signals of serious risks. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1144 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Muhieddine Labban More articles by this author Edoardo Beatrici More articles by this author Dejan K. Filipas More articles by this author Benjamin V. Stone More articles by this author Nguyen David-Dan More articles by this author Elio Adib More articles by this author Kevin R Melnick More articles by this author Alexander P. Cole More articles by this author Stuart R. Lipsitz More articles by this author Toni K. Choueiri More articles by this author Quoc-Dien Trinh More articles by this author Expand All Advertisement PDF downloadLoading ...

Use of phosphodiesterase-5 inhibitors and the incidence of melanoma

IntroductionRecent evidence of a causal link between Phosphodiesterase-5-inhibitor (PDE-5i) use and melanoma has caused concern in PDE-5i use and was even addressed in the 2018 American Urological Association guideline on erectile dysfunction (ED). Given that several studies have affirmed this low probability but statistically significant association, one might expect a shift in melanoma diagnoses since PDE-5is were introduced in 1998. We sought to determine if the introduction of PDE-5i drugs for ED treatment increased incidence of melanoma. MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was used to compare the incidence of melanoma diagnosis in American men between 1973 and 2015, providing over a decade of data before and after PDE-5i introduction in 1998. Interrupted time-series and logistic regression were used to assess this relationship. ResultsOver 43 years, the SEER database has reported 292,166 cases of Melanoma, with males accounting for 53.7% of cases (Standard deviation [SD] 3%, Range 47.5–58.3%). After the introduction of PDE-5i, there was no proportional increase in melanoma diagnoses, in fact demonstrating a 2% lower incidence from prediction models (p < 0.05). ConclusionOur analysis of the SEER database demonstrates that the trend in incidence of melanoma has fallen in the era of PDE-5i use for ED. These findings may be of value in counseling patients anxious about the potential association between PDE-5i use and skin cancer; however, continued research analyzing individual-level risk are needed.

Evaluating the Relationship Among Erectile Dysfunction, Prostate Cancer Treatment Type and Inflatable Penile Prosthesis (IPP) Implantation

ABSTRACT Introduction Sexual health problems affect approximately 60% of male cancer survivors in the U.S. Erectile dysfunction (ED) is the most common sexual health condition men seek professional help for after cancer treatment with some studies reporting ED rates as high as 85% in these men. Inflatable penile prosthesis (IPP) implantation is a safe and highly effective form of ED treatment for patients who fail or cannot tolerate medical therapies. A 2011 study suggested that IPPs are under-utilized by urologists, as less than 1% of men with prostate cancer and ED received IPP following radical prostatectomy or external beam radiation. Objective To better characterize the utilization of IPP treatment, we examined the relationships between ED, prostate cancer treatment type and IPP implantation in a national cohort. Methods We performed a retrospective review of older SEER-Medicare patients who were diagnosed with local/regional prostate cancer between 2006 and 2011 and treated with surgery or radiation for it, with and without ED. Using ICD9/CPT/HCPCS codes we created a cohort of patients who has receipt of surgery or radiation within 3 months of cancer diagnosis as well as diagnosed ED within 5-years after undergoing treatment. Chi-square/Wilcoxon tests were used to detect significant differences between the surgical and radiation treatment groups for ED rates and use of IPP among those with ED. Results Of the 31,854 patients in our cohort, 10,475 (32.9%) received surgery and 21,152 (66.4%) received radiation only. Overall, ED was significantly more common for surgical (65.2%) than for radiation patients (33.8%, p&amp;lt;.001). For the subset of 14,121 patients with ED (overall IPP use=2.5%), IPP implantation was significantly more frequent for surgical patients (n=6,976, IPP use= 3.6%) than for radiation patients (n=7,145, IPP use=1.4%, p&amp;lt;.001). Conclusions Shockingly few (2.5%) prostate cancer patients with ED received IPP, with only 1.4% of radiation patients undergoing IPP vs. 3.6% of RALP patients. IPP under-utilization may be due to greater clinical focus on cancer treatment rather than quality-of-life issues. Discrepancies in ED rates between radiation and surgery may also be partially explained by lack of follow-up standardization and highly variable sexual dysfunction reporting, especially in the radiation literature. These findings highlight the importance of thorough counseling about all treatment options including penile prosthesis surgery for prostate cancer patients with ED. Disclosure No

Characteristics and Longitudinal Patterns of Erectile Dysfunction Drug Use Among Men Who Have Sex with Men in the U.S.

We investigated the longitudinal relationship between erectile dysfunction (ED) drug use with behavioral factors, including substance use and sexual activities in men who have sex with men from the Multicenter AIDS Cohort Study during 1998–2016 (n = 1636). We used a bivariate random-intercept model to evaluate ED drug use along with other behavioral factors to assess relationships between the two outcomes over time on a population level and also at the individual level. Average ED drug use among men who have sex with men (MSM) with HIV was positively correlated with average use of marijuana (r = .19), poppers (r = .27), and stimulants (r = .25). In this group, testosterone use (r = .32), multiple partners (r = .41), insertive anal intercourse with condom (r = .40), and insertive anal intercourse without condom (r = .43) all showed moderate correlations over time with average ED use (p < .001). Associations among MSM without HIV were similar, with average marijuana use (r = .19) and stimulant use (r = .22) being positively correlated with average ED drug use, and were also correlated with having multiple partners (r = .36), insertive anal intercourse with condom (r = .22), and insertive anal intercourse without condom (r = .18) over time. Positive within-individual associations between ED drug use and multiple partners and insertive anal intercourse with and without condom were observed regardless of HIV serostatus. This study showed that MSM who reported use of ED drugs were also, on average, more likely to use recreational drugs and engage in sexual activities, such as having multiple partners and insertive anal intercourse. Within individuals, average ED drug use was also positively correlated with sexual behaviors.

Low-intensity extracorporeal shockwave therapy among urologist practitioners: how the opinion of urologists changed between 2016 and 2019.

Over the past few years, an increase use of low-intensity shockwave therapy (LISWT) for the treatment of erectile dysfunction (ED) has been observed. However, many controversies in the scientific literature about its efficacy still exist. We aimed to investigate changes in the pattern of usage and attitudes toward LISWT for ED among experts over the last years. A dedicated online survey was sent to delegates at the Congress for the EAU Section of Andrological Urology (ESAU) in Prague from 31st October to 1st November 2019. The survey captured demographic data, professional background, and the experience and personal knowledge about LISWT. The results were compared with a previous survey conducted in 2016 and investigating the same topics in order to assess changes in the knowledge and opinion on LISWT over time. Overall, 172 and 192 questionnaires were available from 2019 and 2016, respectively. Participants in the 2019 survey were 80 (45.7%) urologists, 52 (29.7%) uro-andrologists, and 34 (19.4%) residents in urology, from 30 different countries. Compared to the past, we observed an increase of respondents who were familiar with LISWT (75 vs. 95%; p < 0.0001) and who performed LISWT in their routine practice (38% in 2019 vs. 14% in 2016; p < 0.0001). Conversely, no changes in terms of overall perception of treatment efficacy were registered over time (68% in 2019 vs. 72% in 2016 considered LISWT as an effective treatment, respectively (p = 0.5)). An increased proportion of physicians had suggested a wider application of LISWT, and some even advocated its use in nonvasculogenic ED (33% in 2019 vs. 5.9% in 2016; p < 0.0001). The awareness and clinical application of LISWT for ED have increased over time, despite the lack of robust evidence in terms of effectiveness. Further research on the benefit of LISWT is needed to guide physicians in the therapeutic management of ED patients.

018 Erectile Dysfunction Among Male Adult Entertainers: A Survey

Erectile dysfunction (ED) and erectile aids usage has not been evaluated among male adult entertainers. Our goal was to evaluate ED prevalence and use of erectile aids among men in the adult entertainment industry. An online survey was distributed to male adult entertainers through collaboration with the Free Speech Coalition (FSC), the North American Trade Association of the Adult Industry. Surveys were sent via email to those within the Performer Availability Screening Services (PASS) database who met the criteria of being non-transgender men with biological penises and have experience as adult entertainers. The survey anonymously acquired baseline characteristics, use of various erectile aids, and assessed erectile function. Statistical analysis was performed in Microsoft Excel. Of the 98 respondents, 62 met inclusion criteria. The median age was 36 (IQR 28.2 - 45) years. Of those included, 69.3% (43/62) used erectile aids. Of the 43 men who used erectile aids, 58% (25/43) used for both work and personal reasons. In assessing prevalence by age group, erectile aids were used most among young men aged 20-29 (84.2%). Overall, 38.7% (24/62) of men had ED as defined by the International Index of Erectile Function (IIEF) survey. Of note, 26.3% (5/19) of men aged 20-29 had moderate to severe ED.

Platelet-Rich Plasma Therapy for Male Sexual Dysfunction: Myth or Reality?

Platelet-rich plasma (PRP) found its use in treating different conditions and diseases, because concentrated plasma PRP consists of many growth factors. Their interaction with surrounding cells, intracellular matrix, and mediators at the site of injection leads to tissue regeneration. Angiogenic, vasculogenic, and regenerative effects of PRP may be used for erectile dysfunction (ED) and Peyronie's disease (PD) treatment. To present a current data review of preclinical and clinical trials on PRP use for treating ED and PD. Up-to-date literature on PRP use for ED and PD treatment was analyzed. The search was based on Pubmed, Cochrane Library, clinicaltrials.gov databases, with the following key words: "platelet-rich plasma" and/or "erectile dysfunction" and/or "Peyronie's disease" and/or "sexual dysfunction." The main outcome measures for preclinical trials on ED were erectile function, assessed with intracavernous pressure, and pathologic analysis of penile tissue. The main outcome measures for clinical trials on ED included penile duplex Doppler ultrasound scanning and validated questionnaires. The main outcome measures on PD were pathologic analysis of penile tissue for preclinical trials, as well as penile duplex Doppler ultrasound scanning, penile curvature angle measuring, and validated questionnaires for clinical trials. 4 preclinical and 6 clinical trials were described and analyzed in this article. Limitations for both preclinical and clinical trials included small groups, short follow-up periods, a lack of control groups or groups with placebo, and the lack of quality and quantity analysis of PRP. Available data show the lack of adverse reactions with PRP treatment. The studies that we found were limited by small groups. This is why the data on safety and effectiveness should be taken carefully. However, it is important to mention that PRP therapy has the potential for treating male sexual dysfunction and may be useful in andrology. Epifanova MV, Gvasalia BR, Durashov MA, etal. Platelet-Rich Plasma Therapy for Male Sexual Dysfunction: Myth or Reality? Sex Med Rev 2020;8:106-113.

Platelet-Rich Plasma and Treatment of Erectile Dysfunction: Critical Review of Literature and Global Trends in Platelet-Rich Plasma Clinics.

Platelet-rich plasma (PRP) injections have recently been marketed as a form of autologous cell therapy under the banner of regenerative medicine despite limited scientific evidence on its use for treating erectile dysfunction (ED). To evaluate the evidence on PRP treatment for ED and determine the current trends in provision of this treatment. A critical review of the literature on PRP using the PubMed and Embase databases. This narrative review focuses on the clinical use of, regulation of, and evidence for PRP in the treatment of ED. There is a limited number of published peer-reviewed articles demonstrating clinical outcomes pertaining to the use of PRP for ED in human. The technique of PRP application for ED is currently patented, with a global total of 683 registered clinics. The majority of PRP clinics do not provide cost estimates on their websites. Despite a global presence of PRP clinics and ongoing active marketing and public interest in regenerative medicine, no scientific evidence has been published to establish an evidence-based risk-benefit profile for PRP use for ED in humans. Given the limited data on clinical efficacy and potential harmful side effects, there is a need for a proper clinical trial to examine the role of PRP before it is accepted as standard of care in treatment for ED. Scott S, Roberts M, Chung E. Platelet-Rich Plasma and Treatment of Erectile Dysfunction: Critical Review of Literature and Global Trends in Platelet-Rich Plasma Clinics. Sex Med Rev 2019;7:306-312.

Reporting Erectile Function Outcomes After Radiation Therapy for Prostate Cancer: Challenges in Data Interpretation

BackgroundChoice of prostate cancer treatment is frequently influenced by the expected chance of treatment-induced side effects such as erectile dysfunction (ED). However, great discrepancy in cited ED rates exists in the contemporary radiation therapy literature. AimTo analyze the reported ED rates and cause of discrepancies and explore the strengths and limitations in the literature on radiation-induced ED. MethodsWe performed a PubMed literature search and reviewed the literature on ED rates associated with external-beam radiotherapy and brachytherapy from the past 10 years. Eighteen studies were eligible for inclusion and subsequently reviewed. OutcomesVariables required for interpretation of erectile function outcomes, including patient demographics, treatment characteristics, and sexual function outcomes. ResultsA large variety in the reported incidence of ED was found among studies. In part, these differences resulted from large variations in (i) study populations, (ii) patient characteristics, (iii) treatment characteristics, (iv) prescription of androgen deprivation therapy, (v) means of data acquisition, (vi) definitions of ED, (vii) temporal considerations, and (viii) erectile aid use. Relevant data required for adequate appraisal of sexual function outcomes were not always reported. Clinical ImplicationsBased on the present findings, we present general recommendations for reporting of erectile function outcomes after radiotherapy for prostate cancer. These should improve future reports. Strengths and LimitationsThis is the first report that presents general requirements on reporting erectile function outcomes in the setting of radiotherapy for prostate cancer. We did not conduct a formal meta-analysis because we focused on concepts of research design; this might be considered a limitation. ConclusionIn this review, we have highlighted the strengths and deficiencies of the current literature on ED after external-beam radiotherapy and brachytherapy for prostate cancer. We have made general recommendations to achieve some degree of standardization among reports and improve clinical interpretability.Wortel RC, Incrocci L, Muhall JP. Reporting Erectile Function Outcomes After Radiation Therapy for Prostate Cancer: Challenges in Data Interpretation. J Sex Med 2017;14:1260–1269.

Effects of metformin on endothelial health and erectile dysfunction

Erectile dysfunction (ED) affects approximately 18 million American men. ED may be attributed to several etiologies, including arteriogenic, psychogenic, neurogenic, hormonal, drug-induced, and systemic disease or aging related factors. Specific to arteriogenic ED, three major mechanisms have been identified: (I) endothelium-dependent vasodilatory impairment; (II) sympathetic nerve activity elevation; (III) atherosclerotic luminal narrowing. Additionally, these insults have been linked to the insulin resistant state, which in turn is comorbid with obesity, dyslipidemia, diabetes, and hypertension. In this review, we summarize the evidence regarding the impact of metformin—an insulin sensitizer—on the three mechanisms of arteriogenic ED. We report that metformin treatment positively affects two of three pathways, specifically through enhanced endothelium-dependent vasodilation and sympathetic nerve activity attenuation, but does not seem to have a significant impact on hypertension regulation. Given the encouraging data found in both animal and clinical studies, we advocate for further studies on metformin use in ED.

Relationship between Erectile Dysfunction, Comorbidity, and Parkinson's Disease: Evidence from a Population-Based Longitudinal Study.

Background and PurposeTo determine the risk of Parkinson's disease (PD) in relation to erectile dysfunction (ED) based on the National Health Insurance Research Database in Taiwan.MethodsWe identified 3,153 patients who were newly diagnosed with ED between January 1, 2004 and December 31, 2010. A total of 12,612 randomly selected people without ED served as healthy controls. All of the study subjects were followed-up from the index date to the date of PD diagnosis, withdrawal from the National Health Insurance program, or the end of 2012 whichever occurred first.ResultsThe incidence density rate of PD was 1.52-fold higher in the ED cohort than the non-ED cohort (3.44 vs. 1.64 per 1,000 person-years), with an adjusted hazard ratio (HR) of 1.52 [95% confidence interval (CI)=1.09–2.12]. The combined effects on patients with ED and diabetes as well as hypertension showed a significant combined association with the PD risk compared with patients without ED, counterpart comorbidities, or medication use. The adjusted HR of PD for ED was higher for diabetes (2.82, 95% CI=1.42–5.63) and hypertension (2.19, 95% CI = 1.35–3.55).ConclusionsED leads to an increased risk of PD. ED patients with diabetes or hypertension have an elevated risk of PD.

Non-steroidal anti-inflammatory drug (NSAID) use is not associated with erectile dysfunction risk: results from the Prostate Cancer Prevention Trial.

To evaluate the associations of non-steroidal anti-inflammatory drug (NSAID) use with risk of erectile dysfunction (ED), considering the indications for NSAID use. We analysed data from 4 726 men in the placebo arm of the Prostate Cancer Prevention Trial (PCPT) without evidence of ED at baseline. Incident ED was defined as mild/moderate (decrease in normal function) or severe (absence of function). Proportional hazards models were used to estimate the covariate-adjusted associations of NSAID-related medical conditions and time-dependent NSAID use with ED risk. Arthritis (hazard ratio [HR] 1.56), chronic musculoskeletal pain (HR 1.35), general musculoskeletal complaints (HR 1.36), headaches (HR 1.44), sciatica (HR 1.50) and atherosclerotic disease (HR 1.60) were all significantly associated with an increased risk of mild/moderate ED, while only general musculoskeletal complaints (HR 1.22), headaches (HR 1.47) and atherosclerotic disease (HR 1.60) were associated with an increased risk of severe ED. Non-aspirin NSAID use was associated with an increased risk of mild/moderate ED (HR 1.16; P = 0.02) and aspirin use was associated with an increased risk of severe ED (HR 1.16; P = 0.03, respectively). The associations of NSAID use with ED risk were attenuated after controlling for indications for NSAID use. The modest associations of NSAID use with ED risk in the present cohort were probably attributable to confounding indications for NSAID use. NSAID use was not associated with ED risk.

Diffuse Alveolar Hemorrhage Confirmed by Bronchoalveolar Lavage in a Patient with Hemoptysis after Sildenafil Use for Erectile Dysfunction

A 81-year-old man was referred for respiratory failure by emergency medical technicians. He admitted at intensive care unit for ventilator treatment. Several hours before admission, he took sildenafil 100 mg for erectile dysfunction without prescription. The episodes of hemoptysis occurred several hours later. Computed tomography revealed multifocal diffuse ground-glass attenuation in both lungs. And the more we performed bronchoalveolar lavage, the more the color of it was turned into red. We treated him with empirical antibiotics and tranexamic acid, and hemoptysis was stopped in one day after admission. But in the 5th admission day, he died from sepsis combined with pneumonia caused by Acinetobacter baumannii abruptly.

Editorial Comment

Tadalafil has been approved for use in erectile dysfunction and in lower urinary tract symptoms (LUTS). Tadalafil has been shown to improve LUTS in a number of placebo-controlled studies published in the past.1 Despite several possible hypotheses regarding the mechanism of action of this molecule on the lower urinary tract (LUT), this issue is far from resolved. One of the mechanisms of action of tadalafil includes relaxation of the LUT vasculature and consequently increasing the blood flow.2 In the past, a cross-sectional population-based study had studied this issue using contrast-enhanced ultrasonography.

Sildenafil Use and Increased Risk of Incident Melanoma in US Men

The RAS/RAF/mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) kinase/ERK cascade plays a crucial role in melanoma cell proliferation and survival. Sildenafil citrate (Viagra) is a phosphodiesterase (PDE) 5A inhibitor commonly used for erectile dysfunction. Recent studies have shown that BRAF activation down-regulates PDE5A levels, and low PDE5A expression by BRAF activation or sildenafil use increases the invasiveness of melanoma cells, which raises the possible adverse effect of sildenafil use on melanoma risk. To evaluate the association between sildenafil use and risk of incident melanoma among men in the United States. Our study is a prospective cohort study. In 2000, participants in the Health Professionals' Follow-up Study were questioned regarding sildenafil use for erectile dysfunction. Participants who reported cancers at baseline were excluded. A total of 25,848 men remained in the analysis. The incidence of skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), was obtained in the self-reported questionnaires biennially. The diagnosis of melanoma and SCC was pathologically confirmed. We identified 142 melanoma, 580 SCC, and 3030 BCC cases during follow-up (2000-2010). Recent sildenafil use at baseline was significantly associated with an increased risk of subsequent melanoma with a multivariate-adjusted hazard ratio (HR) of 1.84 (95% CI, 1.04-3.22). In contrast, we did not observe an increase in risk of SCC (HR, 0.84; 95% CI, 0.59-1.20) or BCC (1.08; 0.93-1.25) associated with sildenafil use. Moreover, erectile function itself was not associated with an altered risk of melanoma. Ever use of sildenafil was also associated with a higher risk of melanoma (HR, 1.92; 95% CI, 1.14-3.22). A secondary analysis excluding those reporting major chronic diseases at baseline did not appreciably change the findings; the HR of melanoma was 2.24 (95% CI, 1.05-4.78) for sildenafil use at baseline and 2.77 (1.32-5.85) for ever use. Sildenafil use may be associated with an increased risk of developing melanoma. Although this study is insufficient to alter clinical recommendations, we support a need for continued investigation of this association.

A Phase 3, Placebo Controlled Study of the Safety and Efficacy of Avanafil for the Treatment of Erectile Dysfunction After Nerve Sparing Radical Prostatectomy

We evaluated the safety and efficacy of 100 and 200 mg avanafil for the treatment of adult males with erectile dysfunction after bilateral nerve sparing radical prostatectomy. This was a double-blind, placebo controlled, parallel group, phase 3 study in males age 18 to 70 years with a history of erectile dysfunction of 6 months or more after bilateral nerve sparing radical prostatectomy. Patients were randomized to 100 or 200 mg avanafil or placebo (taken 30 minutes before sexual activity) for 12 weeks. Primary end points included successful vaginal insertion (Sexual Encounter Profile [SEP] question 2), successful intercourse (SEP3) and change in score on the erectile function domain of the International Index of Erectile Function (IIEF-EF) questionnaire. A total of 298 patients were randomized and 84.6% completed the study. At baseline 16.1% were age 65 years or older and 71.5% had severe erectile dysfunction (mean overall IIEF-EF domain score 9.2). After 12 weeks there were significantly greater increases in SEP2 and SEP3 and change in mean IIEF-EF domain score with 100 and 200 mg avanafil vs placebo (p <0.01). Following dosing with avanafil 36.4% (28 of 77) of sexual attempts (SEP3) at 15 minutes or less were successful vs 4.5% (2 of 44) for placebo (p <0.01). Avanafil was generally well tolerated. No serious adverse events were reported and fewer than 2% of patients discontinued the study due to an adverse event. Avanafil in 100 and 200 mg doses was effective and well tolerated in improving erectile function after prostatectomy. Results suggest a rapid onset of action and sustained duration of effect, with all 3 primary end points being achieved at both dose levels.

The psychological effects of recreational PDE5 inhibitor use

The availability of PDE5 inhibitors has significantly altered the way in which erectile dysfunction (ED) is treated. Some major issues have emerged since the advent of PDE5 inhibitor use for ED, especially in relation to recreational use in young, healthy men and the role of confidence in erectile ability.