PDE5i Use Research Articles

Rethinking of phosphodiesterase 5 inhibition: the old, the new and the perspective in human health.

The phosphodiesterases type 5 (PDE5) are catalytic enzymes converting the second messenger cyclic guanosine monophosphate (cGMP) to 5' GMP. While intracellular cGMP reduction is associated with several detrimental effects, cGMP stabilization associates with numerous benefits. The PDE5 specific inhibitors, PDE5i, found their explosive fortune as first-line treatment for erectile dysfunction (ED), due to their powerful vasoactive properties. The favorable effect for ED emerged as side-effect when PDE5i were originally proposed for coronary artery disease (CAD). From that point on, the use of PDE5i captured the attention of researchers, clinicians, and companies. Indeed, PDE5-induced intracellular cGMP stabilization offers a range of therapeutic opportunities associated not only with vasoactive effects, but also with immune regulatory/anti-inflammatory actions. Chronic inflammation is acknowledged as the common link underlying most non-communicable diseases, including metabolic and cardiac diseases, autoimmune and neurodegenerative disorders, cancer. In this scenario, the clinical exploitation of PDE5i is undeniably beyond ED, representing a potential therapeutic tool in several human diseases. This review aims to overview the biological actions exerted by PDE5i, focusing on their ability as modulators of inflammation-related human diseases, with particular attention to inflammatory-related disorders, like cardiac diseases and cancer.

Retzius sparing robot-assisted radical prostatectomy: optimizing functional results.

The aim of this study is to critically evaluate the existing body of evidence regarding the efficacy of Retzius-sparing radical prostatectomy (RS-RARP) in achieving improved functional outcomes. Moreover, we explored possible strategies to further optimize functional outcomes. Following PRISMA guidelines, a systematic review (PROSPERO ID CRD42024539915) was performed on 9th September 2023 on PubMed, Scopus, and Web of Science. Only original articles in the English language reporting functional outcomes after RS-RARP were included. Overall, the search string yielded 99 results on PubMed, 122 on Scopus, and 120 on Web Of Science. After duplicate exclusion, initial screening and eligibility evaluation, a total of 47 studies were included in the qualitative analysis, corresponding to a cohort of 13.196 patients. All studies reported continence recovery. RS-RARP appeared to achieve better and faster continence recovery compared to S-RARP. However, it should be noted that continence definition was heterogeneous and not based on validated condition-specific questionnaires. Seven (15%) studies provided for any sort of rehabilitation for urinary incontinence after RS-RARP. 22 studies analyzed potency recovery rates, showing no difference between RS-RARP and S-RARP. The evaluation of this outcome poses a great challenge due to the lack of standardized assessment tools and reporting methods. Only two studies reported on the consistent use of post-operative PDE5i as penile rehabilitation. The current review highlights the satisfactory functional results of Retzius-sparing robot assisted radical prostatectomy, which holds true irrespective of disease stage and prostate volume, with promising results even in patients previously treated for BPH or in the salvage setting. How can we optimize those results? The answer does not probably lie in further refinement of the surgical technique, but in giving greater attention to patient counselling and rehabilitation strategies in order to minimize regret and maximize satisfaction.

(PM-17) THE ROLE OF PHOSPHODIESTERASE-5 INHIBITORS IN THE TREATMENT OF COMPLEX PENILE WOUNDS: A CASE REPORT AND LITERATURE REVIEW

Abstract Introduction/Objective Phosphodiesterase-5 inhibitors (PDE5i) are traditionally employed for the management of erectile dysfunction and lower urinary tract symptoms. However, their role in the healing of complex penile wounds remains scarcely discussed. This study aims to describe the case of a 27-year-old man who suffered from penile strangulation, treated with sildenafil. Additionally, a literature review concerning the use of PDE5i for the treatment of complex penile injuries will be conducted. Methods A 27-year-old man presented to the emergency room after a self-induced penile strangulation using a ring placed at the base of the penis. Extensive necrosis of the corpus cavernosum was identified through magnetic resonance imaging. Considering the psychosocial implications of penile amputation, organ preservation was chosen, and conservative treatment with sildenafil and daily local dressings was initiated. Thirty days after admission, Doppler ultrasound revealed symmetrical corpus cavernosum with normal echogenicity and usual blood flow patterns. Subsequently, the patient underwent superficial necrotic tissue debridement followed by partial skin grafting in a second stage, leading to hospital discharge after 55 days of hospitalization. Results PDE5 inhibitors enhance nitric oxide bioavailability, promoting vasodilation and improved tissue oxygenation, thereby facilitating various phases of the healing process. Evidence indicates their benefit in microvascular perfusion in skin and soft tissues. Reports suggest satisfactory outcomes of topical PDE5i application in radiation-induced lesions, implying their role in epidermal cell expansion, reduction of inflammatory infiltrates, enhanced vascularization, and decreased collagen deposition. Conclusion This study presents a successful case of sildenafil use in treatment of a complex penile wound, shedding light on an unconventional application of PDE5i. Financing No conflict.

(117) Is Platelet-Rich Plasma Effective and Safe for Managing Erectile Dysfunction? A Meta-Analysis of Before-After Data from Clinical Studies

Abstract Introduction Erectile dysfunction (ED) is common health issues among men with increasing prevalence along with age. With the advancement of technology, the aim of therapy for ED is start to shift in reversing the pathology and not only relieving the symptoms. Platelet-rich plasma (PRP) are one of the regenerative modalities that has gained popularity in many medical disciplines. Many studies have been conducted that favour PRP in improving erectile function. However, no relevant meta-analysis of PRP have been performed to date. Objective A single-arm meta-analysis were conducted to evaluate the outcome of PRP for the treatment of ED based on the data before and after the procedures. Methods We systematically searched PubMed, Embase, Scopus in June 2023 to find the relevant articles based on the Preferred Reporting Items for Systematic Review and Meta-analysis statement. All randomized controlled trials (RCTs), observational, and case control studies in English with 10 or more subjects and a minimum of 1 month follow-up after PRP treatment reporting International Index of Erectile Function-Erectile Function (IIEF-EF) score were included. Pooled analysis on outcomes that were reported in at least 2 studies were performed using RevMan 5.4 and STATA18 with 95% confidence intervals (CIs). We also conduct heterogeneity test and a leave-one-out sensitivity analysis. Results A total of three RCTs, three observational studies and one case-control study, comprising 236 patients, were included from 183 studies identified. The pooled analysis showed that PRP injection significantly increased the IIEF-EF score by 3.87 (95% CI: 2.92, 4.83, p<0.00001), 3.01 (95% CI: 2.27, 3.74, p<0.0001), 3.29 (95% CI: 2.26, 4.32, p<0.00001), at 1, 3, and 6, months follow-up. Subgroup analysis of IIEF-EF based on the use of PDE5i in the protocol or during follow-up period also found the same finding result. The proportion of patient who met MCID after 6 months of follow of was 70% (95% CI: 59%, 80%). In term of penile hemodynamic, a significant improvement was found in peak systolic velocity and end diastolic velocity at the end-point of follow-up. On contrary, there was no significant improvement were found for IIEF score of intercourse satisfaction and overall satisfaction domain. The most common complication reported were transient subcutaneous bruising. Two cases reported a formation of painless plaque but no other major adverse events were reported. Consistent result was found after a leave-one-out sensitivity analysis. Conclusions PRP is a promising restorative modality for ED with improvement in IIEF-EF score and penile hemodynamic. However, further studies and human trials are required to confirm the efficacy and durability of this novel treatment as well as to find out the best protocol of administration. Disclosure No.

(015) The Association Between Prostate Volume and Erectile Function Recovery Following Radical Prostatectomy

Abstract Introduction The relationship between prostate volume (PV) and erectile function recovery (EFR) after radical prostatectomy (RP) has not been well studied. Objective We aimed to evaluate PV as a predictor of EFR 24 months after RP. Methods We included men who underwent RP with surgeon-reported nerve-sparing score (NSS) and 2-year follow up who had documentation of pre-RP PV on MRI and baseline functional erections (pre-RP IIEF-EFD scores ≥ 24). Demographics, ED-related comorbidities, pathological features, PDE5i use, and total testosterone (T) levels were recorded. At 12 months post-RP, patients scored PDE5i use 0-3; 0 never, 1 sometimes, 2 regularly, 3 routinely. NSS on each side (R/L) was scored on a 1-4 scale: 1 complete preservation, 2 near-complete preservation, 3 partial resection, 4 complete resection. Scores of 1 or 2 indicate nerve-sparing and scores of 3 or 4 indicate non-nerve-sparing. We then classified overall NS status as bilateral, unilateral, or non-spared. At 24 months post-RP, EFD score ≥ 24 defined functional erections, ≤ 10 severe ED. Multivariable analysis (MVA) evaluated predictors of EFD score ≥ 24 as well as EFD ≤ 10 after RP; patient age, number of comorbidities, baseline EF, NSS, PDE5i use, and PV were analyzed. Results 1741 men were included. Median age was 60 (55, 65) years. 36% had ≥ 2 comorbidities. Median PV was 33 (26, 44) mL with 12% having PV ≥ 60 mL. Median pre-RP IIEF-EFD score was 29 (27, 30). Grade group 1, 2, 3, 4 and 5 comprised 12%, 68%, 15%, 2%, and 3% of the cohort, respectively. NSS: bilateral (82%), unilateral (15%), non-spared (3%). Median PDE5i use score within 4 weeks of the 12 month post-RP visit was 1 (0, 1); reported PDE5i use was 44% never, 39% sometimes, 13% regularly, and 4% routinely. At 24 months post-RP, median EFD was 22 (9, 28), and 56% had EFD < 24. Men with post-RP EFD < 24 had greater PV (41 ± 26 mL) vs men with EFD ≥ 24 (36 ± 17 mL, p<0.001). 67% of the men with EFD < 24 had a PV ≥ 60 mL vs 33% of men with EFD ≥ 24 (p=0.02). On MVA, predictors of EFD ≥ 24 included bilateral NS, age and PV. Predictors of EFD ≤ 10 included bilateral NS and age. At 24 months post-RP, neither routine PDE5i use nor a higher comorbidity index were predictive of EF outcome. Conclusions Among men with functional erections pre-RP, larger PV is associated with a poorer EFR at 24m post-RP independent of degree of nerve-sparing, age, and PDE5i use. Disclosure No.

(162) Evaluating the Effectiveness of Testosterone Therapy Combined with PDE5 Inhibitors in Enhancing Erectile Function in Eugonadal Men

Abstract Introduction Historically, testosterone therapy (TTh) is not indicated in eugonadal men with erectile dysfunction (ED). Moreover, the 2018 AUA Guidelines state that TTh is not indicated as monotherapy for men suffering from ED but should be considered as combination therapy with PDE5i, as TTh may increase the efficacy of PDE5i therapy. Objective We investigated the benefits of providing TTh in combination with PDE5i therapy in marginally eugonadal men to determine its efficacy in improving erectile function. Methods A retrospective chart review was performed on men presenting with ED to an academic institution’s Men’s Health Clinic from 2010 to 2022. Objective data was gathered on key variables that affected patient-reported outcomes of ED, including age at presentation and comorbidities, as well as use of TTh and use of oral PDE5i. 177 eugonadal men were selected with the criteria of testosterone levels >300 ng/dL on initial presentation. Results were then statistically analyzed using a two-tailed student’s T test in R and p-values to determine the significance between variables and outcomes in ED. Results Out of our cohort of 179 eugonadal men presenting with ED, 42 patients were continued or started on concurrent TTh with oral PDE5i therapy added, and 83 were started on PDE5i monotherapy. Men in the dual-therapy group excluding those already on TTh began with a pre-therapy testosterone mean of 412.3 ng/dL compared to 443.0 ng/dL which was insignificant (p=0.22). There were no significant differences in presenting age (p=0.61) or comorbidities including hypertension (p=0.89) and diabetes (p=0.63) between the two groups. Additionally, there were no significant differences in lab values of HgA1c (p=0.34), cholesterol (p=0.80), triglycerides (p=0.27), or LDL (p=0.89). However, there was a lower initial HDL in the combination group of 45.1 mg/dL compared to 55.8 mg/dL (p = 0.036). Men in the dual-therapy group were more likely to report subjective improvement in ED symptoms compared to men taking PDE5is alone. This was supported by 33/42 (78.6%) of men in the dual therapy group reporting improved erectile function compared to 49/83 (59.0%) of men in the PDE5i only group (p = 0.029). Conclusions In conclusion, these results demonstrate that treatment of eugonadal men with concurrent TTh and PDE5i therapy demonstrated a significant improvement in erectile function as compared to PDE5i therapy alone. These findings suggest consideration of testosterone therapy in addition to PDE5i in clinical practice when treating marginally eugonadal men presenting with ED. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast Investor: Sprout.

Oral phosphodiesterase type 5 inhibitors and priapism: A VigiBase analysis.

To explore the differences of priapism events among a diverse cohort taking erectogenic medicines (i.e., phosphodiesterase type 5 inhibitors [PDE5i] and intracavernousal drugs). We queried the World Health Organization global database of individual case safety reports (VigiBase) for records of the adverse drug reactions (ADR) with sildenafil, tadalafil, avanafil, vardenafil, papaverine, and alprostadil. Disproportionality analyses (case/non-case approach) were performed to assess the reporting odds ratio (ROR) of priapism reporting in PDE5i consumers compared to intracavernousal drug recipients. From a total of 133 819 ADR events for erectogenic medications, 632 were priapism (PDE5is: n = 550, 0.41%; intracavernousal drugs: n = 82, 9.92%). Priapism disproportionality signals from intracavernousal drugs were 25 times stronger than PDE5is (ROR = 34.7; confidence interval [CI] 95%: 27.12-43.94 vs. ROR = 1.38; 95% CI: 1.24-1.54). For all PDE5i agents, the 12-17 years age group had the highest ROR (9.49, 95% CI: 3.76-19.93) followed by 2-11 years (4.31, 95% CI: 1.57-9.4). Disproportionality signals for consumers under 18 for both all PDE5is as a whole (ROR = 4.57, 95% CI: 2.48-7.73) and sildenafil (ROR = 4.89, 95% CI: 2.51-8.62) were stronger than individuals 18 or older (ROR = 1.06, 95% CI: 0.93-1.21 and ROR = 1.08, 95% CI: 0.91-1.26, respectively). PDE5i use shows disproportionate priapism signals which are higher in young patients.

(016) The Effect of Phosphodiesterase-5-inhibitor on Female Sexual Function: A Systematic Review and Meta-analysis

Abstract Introduction The link between the attainment of healthy sexual function and a high quality of life in women is well established. However, while the management of male sexual dysfunction has been afforded huge research and development, far less time and effort has been lent in the achievement of successful remedies for females experiencing sexual dysfunction. The use of oral phosphodiesterase type 5 (PDE5) inhibitors, such as Sildenafil, has been the mainstay of treatment for male sexual dysfunction for the last two decades. PDE5 inhibitors have been shown to initiate penile erection, through smooth muscle relaxation and the subsequent increase in intracellular cGMP levels. PDE5-containing cells, similar to those found in the penis, have also been confirmed within the clitoris. No previous pooled analysis has been performed, looking at the possible effect of PDE5 inhibitors on female sexual function, in a population comprising of heterosexual cisgender population. Objectives We aimed to perform a systematic review and meta-analysis of the best possible available studies, to evaluate the efficacy and safety of PDE5 inhibitors versus placebo when used in an exclusively female population. Methods We conducted a comprehensive search of electronic databases (MEDLINE, PubMed, EMBASE, CINAHL, CENTRAL, SCOPUS, Google Scholar, Web of Science, EBSCO Host, TRIP and Epistemonikos), identifying studies comparing the PDE5 inhibitors versus placebo, and the resultant effect on female sexual function. The Cochrane risk-of-bias tool for RCTs and the Newcastle-Ottawa scale for observational studies were used to assess the included studies. Random effects modelling was used to calculate pooled outcome data. Results Searches of electronic databases resulted in 67 articles, from which 13 randomised control trials (RCTs) met the eligibility criteria, enrolling a total of 1605 patients. The use of PDE5 inhibitor was associated with a significantly improved orgasm satisfaction (P=0.01), increased sexual arousal (P=0.02), increase in sexual satisfaction (P=0.007) when compared to placebo. The use of PDE5i was also found to have a significant association with the incidence of headaches (P<0.0001) and flushing (P<0.00001). Conclusions Our meta-analysis demonstrated that the use PDE5 inhibitor was associated with a significantly higher attainment of orgasm satisfaction, sexual arousal, and sexual satisfaction when administered to a solely female population, when compared with placebo. However, the use of PDE5 inhibitors was also associated with a significantly increased risk of headache and flushing. Further large-scale high-quality RCTs are required in order to further evaluate the potential role of PDE5i’s in women, particularly in those suffering from significant sexual dysfunction. These future studies should focus on a more homogenous patient group, with stricter definitions of inclusion criteria. Disclosure

PD11-03 THE USE OF PHOSPHODIESTERASE 5 INHIBITORS IS NOT ASSOCIATED WITH OCULAR ADVERSE EVENTS

You have accessJournal of UrologyCME1 Apr 2023PD11-03 THE USE OF PHOSPHODIESTERASE 5 INHIBITORS IS NOT ASSOCIATED WITH OCULAR ADVERSE EVENTS Federico Belladelli, Shufeng Li, Chiyuan A. Zhang, Francesco Del Giudice, Frank Glover, Wade Muncey, Nicolas Serranio, Satvir Basran, Francesco Montorsi, Andrea Salonia, and Michael Eisenberg Federico BelladelliFederico Belladelli More articles by this author , Shufeng LiShufeng Li More articles by this author , Chiyuan A. ZhangChiyuan A. Zhang More articles by this author , Francesco Del GiudiceFrancesco Del Giudice More articles by this author , Frank GloverFrank Glover More articles by this author , Wade MunceyWade Muncey More articles by this author , Nicolas SerranioNicolas Serranio More articles by this author , Satvir BasranSatvir Basran More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Andrea SaloniaAndrea Salonia More articles by this author , and Michael EisenbergMichael Eisenberg More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003251.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Phosphodiesterase-5 inhibitors (PDE5i) are the first-line line treatment for men with ED. The use of PDE5I has recenty been linked to several ocular side effects, such as serous retinal detachment (SRD), retinal vascular occlusion (RVO), and ischemic optic neuropathy (ION). However, the risk factors for major ocular events and ED overlap suggesting that the association may not be causative. The current study investigated the risk for SRD, RVO, and ION in patients using PDE5Is. METHODS: We utilized the IBM® MarketScan® (2007 to 2016) Commercial and Medicare Supplemental Databases (v 2.0, DOI: 10.57761/ray7-1g16). Cox proportional hazard models were applied to calculate the risk of ocular events after the diagnosis and or treatment of ED (i.e. PDE5i, penile injection/urethral suppositories, penile prosthesis placement) while adjusing for relevant comorbidities. As a further analysis, the use of PDE5i in men with BPH was also examined. RESULTS: In total, 1,565,006 men with an ED diagnosis were identified. Among them, 525,624 (33.6%) were treated with a PDE5i. In total, 1,806,803 men with a BPH diagnosis were observed during the study period with 141,607 (7.8%) treated with a PDE5i. On adjusted analysis, PDE5i use was not consistently associated with SRD, ION, and any ocular event when compared to ED diagnosis and other ED treatments. However, men who received a penile prosthesis had a higher risk of ocular events RVO (HR: 2.36; 95% CI: 1.81–3.09). In addition, PDE5i use was associated with SRD, RVO, and ION in the BPH cohort. In fact, BPH patients using 5a reductase/alpha blocker or prostatectomy had the highest risk of ocular events. CONCLUSIONS: In the current report, no consistent association with PDE5i use and adverse ocular events (i.e. SRD, RVO, and ION) was identified. For erectile dysfunction, men requiring more invasive treatment of ED (i.e. men with more severe ED who required more invasive treatments) carried the highest risk of adverse ocular events. The link between PDE5i use and ocular events is consistent with biases related to common risk factors suggesting patient counseling about this association is unnecessary. Source of Funding: Data for this project were accessed using the Stanford Center for Population Health Sciences Data Core. The PHS Data Core is supported by a National Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award (UL1TR003142) and from Internal Stanford funding. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e333 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Federico Belladelli More articles by this author Shufeng Li More articles by this author Chiyuan A. Zhang More articles by this author Francesco Del Giudice More articles by this author Frank Glover More articles by this author Wade Muncey More articles by this author Nicolas Serranio More articles by this author Satvir Basran More articles by this author Francesco Montorsi More articles by this author Andrea Salonia More articles by this author Michael Eisenberg More articles by this author Expand All Advertisement PDF downloadLoading ...

MP45-16 SEXUAL HEALTH IMPLICATIONS ASSOCIATED WITH PSYCHOTROPIC MEDICATION USAGE IN ADOLESCENTS DURING THE COVID-19 PANDEMIC: ANALYSIS OF A FEDERATED RESEARCH NETWORK

You have accessJournal of UrologyCME1 Apr 2023MP45-16 SEXUAL HEALTH IMPLICATIONS ASSOCIATED WITH PSYCHOTROPIC MEDICATION USAGE IN ADOLESCENTS DURING THE COVID-19 PANDEMIC: ANALYSIS OF A FEDERATED RESEARCH NETWORK Joshua White, Marco Rivero, Jesse Ory, and Ranjith Ramasamy Joshua WhiteJoshua White More articles by this author , Marco RiveroMarco Rivero More articles by this author , Jesse OryJesse Ory More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003291.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Psychotropic medications have a significant impact on sexual health. Long-term usage is strongly associated with dyspareunia, decreased libido, hypogonadism and erectile dysfunction. We hypothesized that the prescription rates for psychotropic medications increased in adolescent patients during the COVID-19 pandemic because of the unprecedented stress levels on youth in isolation. Therefore, we evaluated the prescription rates of psychotropic medications as well as concurrent use of PDE5i in adolescent patients during the COVID-19 pandemic compared to the pre-pandemic era. METHODS: We utilized data generated from TriNetX Research Network to conduct a retrospective matched cohort study. Adolescent patients aged 10-19 presenting for outpatient evaluation were placed into two cohorts: 1) outpatient evaluation before and 2) during the COVID-19 pandemic. Patients with prior psychiatric diagnoses and those with prior use of psychotropic medications were excluded. The outcomes of interest were new prescriptions within 90 days of outpatient evaluation. Propensity score matching was performed using logistic regression to build cohorts of equal size. RESULTS: A total of 1,612,283 adolescents pre-COVID-19 and 1,008,161 adolescents presenting during the COVID-19 pandemic for outpatient evaluations were identified. After propensity matching, a total of 1,005,408 adolescents were included in each cohort each with an average age of 14.7 ± 2.84 and 52% female and 48% male. Prescribing of antipsychotics and benzodiazepines were more frequent during the pandemic for adolescents (RR: 1.58, 95% CI 1.01-2.2). However, they were less likely to receive antidepressants (Risk Ratio (RR): 0.6, 95% Confidence Interval (CI) 0.57-0.63), anxiolytics (RR: 0.78, 95% CI 0.75-0.81), stimulants (RR: 0.26, 95% CI 0.25-0.27), as well as mood stabilizers (RR: 0.44, 95% CI 0.39-0.49). Erectile dysfunction requiring oral PDE5i in this cohort was more frequent during the pandemic for adolescents (RR: 1.53, 95% CI 1.05-2.01). CONCLUSIONS: The rates of antipsychotic and benzodiazepine prescriptions increased during the COVID-19 global pandemic compared to preceding years. This coincided with a statistically significant increase in the prescription of PDE5i for erectile dysfunction. Adolescents may face an increased risk of sexual dysfunction as both their illness and the medications they are prescribed both have a positive association with sexual dysfunction. Clinicians must be cognizant of the fact that adolescents may face an increased risk of medication related sexual dysfunction. Source of Funding: NIH health grant RO1 DK130991 and Clinician Scientist Development Grant from the American Cancer Society to RR © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e627 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua White More articles by this author Marco Rivero More articles by this author Jesse Ory More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

Long-term effects of phosphodiesterase-5 inhibitors on cardiovascular outcomes and death: a systematic review and meta-analysis of cohort studies

Abstract Background Phosphodiesterase type 5 inhibitors (PDE-5i), which are widely used for the treatment of erectile dysfunction, have been found to exhibit systemic vascular benefits by improving endothelial function possibly lowering the risk for cardiovascular events and death. Purpose We sought to evaluate the effects of PDE5i on long-term cardiovascular outcomes and mortality. Methods A comprehensive search of electronic databases was conducted up to February 28, 2022. Cohort studies comparing PDE5i treatment at any dose with placebo or no treatment and a minimum follow-up duration of 6 months were considered eligible. The outcomes of interest were: (1) major adverse cardiovascular events (MACE) and (2) all-cause mortality. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated. Results Eight trials were included (1,152,106 subjects, 8.5% treated with PDE5i). All were males [median age 61.5 years (range 30–72.8)]. The median follow-up duration was 3.8 years (range 2.3–7.5) across the studies. PDE5i use was associated with significant reduction in the composite of MACE [RR 0.79, 95% confidence intervals (CI) 0.69–0.91] (Figure 1). In addition, the analysis of pooled data from 5 studies, after removal of a study with a relatively small sample size, demonstrated that the use of PDE5i was associated with a significantly lower risk of all-cause mortality (RR 0.70, 95% CI 0.53–0.91) (Figure 2). Focusing on patients with a history of coronary artery disease, PDE5i was also found to reduce the risk of all-cause mortality by 15% (RR 0.85, 95% CI 0.74–0.98). Conclusion The use of PDE5i in men with or without known coronary artery disease was associated with a lower risk of cardiovascular events and overall mortality. This information underlines that PDE5i could provide considerable clinical benefit beyond the treatment of ED and could instigate the conduction of further, large-scale randomized clinical trials. Funding Acknowledgement Type of funding sources: None.

Erectile dysfunction, phosphodiesterase-5 inhibitor use and risk of cardiovascular disease and mortality in people with diabetes: A systematic review and meta-analysis

BackgroundPhosphodiesterase-5 inhibitors (PDE5-Is), used in the management of erectile dysfunction (ED), have potential cardioprotective benefits. The impact of PDE5-Is on reducing adverse cardiovascular outcomes in patients with diabetes mellitus (DM) and ED is uncertain. Using a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs), we evaluated if (i) the association of PDE5-Is in people with ED and DM and their risk of cardiovascular disease (CVD) and mortality and (ii) ED confers an excess risk of CVD and mortality in patients with DM compared with no DM. MethodsStudies were identified from MEDLINE, Embase, the Cochrane Library, Web of Science citation search and search of bibliographies to April 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. ResultsEighteen unique studies reported on the cardiovascular impact of ED in patients with and without DM. In the general population, the RRs (95% CIs) of ED for composite CVD/MACE, all-cause mortality, CHD and stroke were 1.43 (1.31–1.55), 1.47 (1.31–1.65), 1.59 (1.39–1.82), and 1.34 (1.15–1.56), respectively. The respective estimates were 1.68 (1.15–2.45), 1.40 (0.90–2.18), 1.41 (1.24–1.61) and 1.32 (1.09–1.60) in the diabetes population. Interaction analyses suggested similar risk in both populations. Six studies reported the cardiovascular effects of PDE5-Is in people with ED and DM. Limited RCT data showed no significant differences in the risk of major adverse cardiac event (MACE), coronary heart disease (CHD) and all-cause mortality comparing PDE5-I use with non-use: RRs (95% CIs) of 3.47 (0.17–69.19), 1.31 (0.10–16.54) and 0.35 (0.12–1.05), respectively. ConclusionsED confers no excess risk of CVD and mortality in patients with DM compared with no DM. Limited and inadequately powered data shows no significant differences in the risk of adverse cardiovascular outcomes comparing use of PDE5-Is with non-use in patients with ED and DM.PROSPERO Registration: CRD42022324537

Erectile dysfunction as a marker of endocrine and glycemic disorders

PurposeThe aim of this study was to evaluate in a population of patients with erectile dysfunction (ED): (a) the prevalence of a previously unknown endocrine/glycemic disorders; (b) the correlation between ED severity and endocrine/glycemic disorders.Methods1332 patients referred for ED from 2013 to 2020 were included. The ED diagnosis was made using the International-Erectile-Function-Index-5 questionnaire. ED severity was considered according to presence/absence of spontaneous erections, maintenance/achievement deficiency. All patients were subjected to search for sociodemographic and clinical characteristics: age, ethnicity, marital status, previous use of PDE5i, previous prostatectomy, diabetes mellitus (DM), prediabetes, endocrine dysfunctions.ResultsThe mean ± SD age was 54.3 ± 13.7 years. The 19.1% (255/1332) of patients were already in treatment for prediabetes/diabetes or endocrine dysfunctions. Among the remaining 1077, the prevalence of previously unknown endocrine and glycemic disorders was 30% (323/1077). Among them, 190/323 subjects (58.8%) were affected by hypogonadism, with high estradiol level observed in 8/190 (4.2%). The prevalence of new glycemic alterations was 17.3% (56/323) [specifically, 32/56 (57.1%) DM, and 24/56 (42.9%) prediabetes]. A thyroid dysfunction was observed in 40/323 subjects (12.3%) and hyperprolactinemia in 37/323 (11.5%). Patients with new diagnosis of DM showed more severe form of ED compared to the total group {difficulty in the achievement of erection: 46/56 [82.2%, vs 265/1332 (19.9%), p < 0.05]; absence of spontaneous erection 23/56 [41.1%, vs 321/1332 (24.1%), p < 0.05]}.ConclusionED is an early marker of endocrine/glycemic disorder, and a previously unknown dysfunction was found in more than a quarter of patients. A newly diagnosed DM is associated with ED severity, especially in elderly man and in presence of hypertension.

Pretransplant Medications and Primary Graft Dysfunction Risk in Lung Transplant Recipients

PurposePrimary graft dysfunction (PGD) is a serious complication of lung transplantation marked by acute lung injury and reperfusion edema in the immediate post-transplant period, but the effect of pretransplant medication use on PGD risk is not known. We hypothesized that some pretransplant medications could be associated with PGD risk, particularly those with anti-inflammatory activity (macrolide antibiotics, statins) and vasoactives (anti-hypertensives, pulmonary vasodilators).MethodsWe reviewed a previously published cohort of adult patients who underwent lung transplant in our program between 2004 and 2016. The primary outcome was the development of grade 3 PGD (PGD3) at 48- or 72-hours post-transplant. We assessed use of medication classes from listing records, with a sample of these verified against transplant admission records. We evaluated the relationship between pretransplant medication class and PGD3 using Fisher's exact testing and multivariable logistic regression, adjusting for known PGD risk factors including recipient pulmonary diagnosis, body mass index, mean pulmonary arterial pressure, donor age and donor smoking status.Results19% of 330 patients who underwent lung transplant during the study timeframe developed PGD3. Phosphodiesterase inhibitor (PDE5i), endothelin receptor antagonist, proton pump inhibitor, and beta blocker (BB) use showed unadjusted associations with PGD3 risk, and PDE5 and BB use remained associated after adjustment (table 1). BB use remained significantly associated after further correction for left ventricular end diastolic pressure.ConclusionOur exploratory analysis showed no association between pretransplant use of medications with anti-inflammatory properties - including macrolides and statins - and PGD3 risk, but PDE5i and BB use increased PGD risk despite adjustment for indication, suggestive vasoactive medications may play a role. These associations would benefit from further study. Primary graft dysfunction (PGD) is a serious complication of lung transplantation marked by acute lung injury and reperfusion edema in the immediate post-transplant period, but the effect of pretransplant medication use on PGD risk is not known. We hypothesized that some pretransplant medications could be associated with PGD risk, particularly those with anti-inflammatory activity (macrolide antibiotics, statins) and vasoactives (anti-hypertensives, pulmonary vasodilators). We reviewed a previously published cohort of adult patients who underwent lung transplant in our program between 2004 and 2016. The primary outcome was the development of grade 3 PGD (PGD3) at 48- or 72-hours post-transplant. We assessed use of medication classes from listing records, with a sample of these verified against transplant admission records. We evaluated the relationship between pretransplant medication class and PGD3 using Fisher's exact testing and multivariable logistic regression, adjusting for known PGD risk factors including recipient pulmonary diagnosis, body mass index, mean pulmonary arterial pressure, donor age and donor smoking status. 19% of 330 patients who underwent lung transplant during the study timeframe developed PGD3. Phosphodiesterase inhibitor (PDE5i), endothelin receptor antagonist, proton pump inhibitor, and beta blocker (BB) use showed unadjusted associations with PGD3 risk, and PDE5 and BB use remained associated after adjustment (table 1). BB use remained significantly associated after further correction for left ventricular end diastolic pressure. Our exploratory analysis showed no association between pretransplant use of medications with anti-inflammatory properties - including macrolides and statins - and PGD3 risk, but PDE5i and BB use increased PGD risk despite adjustment for indication, suggestive vasoactive medications may play a role. These associations would benefit from further study.

Treatment of Poor Sperm Quality and Erectile Dysfunction With Oral Pentoxifylline: A Systematic Review.

Background: Pentoxifylline (PTX) is a member of methylxanthine chemicals and a type of non-selective phosphodiesterase-5 inhibitors, which has been used in male infertility treatment to improve sperm quality and erectile dysfunction (ED) treatment. Mutually tight associations existed between ED and male infertility. Using PTX might kill two birds with one stone by improving sperm quality and erectile function in infertile men with ED. Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were searched by October 2021. Based on available evidence from observational studies and randomized-controlled trials (RCTs), we conducted a systematic review to summarize the efficacy and safety of PTX in treating ED and male infertility. The protocol of the article was registered and updated in PROSPERO (CRD42021291396). Results: From 202 records, eight studies (7 RCTs) evaluating the role of PTX in ED and three studies (2 RCTs) assessing the efficacy of PTX in male infertility were included in the systematic review. Three studies (100.00%) and two studies (100.00%) reported the beneficial role of PTX in improving sperm progressive motility and normal sperm morphology rate, respectively. In contrast, only one study (33.33%) indicated the favorable role of PTX in enhancing sperm concentration. As for ED, three (60.00%) studies supported the treatment role of PTX alone in ED, and two studies (66.67%) favored the combination use of PTX and selective PDE5Is compared with selective PDE5Is alone. Safety analysis showed that PTX was a well-tolerated drug in ED and male infertility treatment. Conclusion: Given the association between ED and male infertility and satisfying findings from available evidence, PTX administration for the simultaneous treatment of poor sperm quality and mild ED in infertile men will highly enhance the treatment compliance. However, the finding should be treated carefully until validated by further studies.

Facing Counterfeit Medications in Sexual Medicine. A Systematic Scoping Review on Social Strategies and Technological Solutions.

IntroductionThe counterfeit phenomenon is a largely under-reported issue, with potentially large burden for healthcare. The market for counterfeit drugs used in sexual medicine, most notably type 5 phosphodiesterase inhibitors (PDE5i), is rapidly growing.AimsTo report the health risks associated with the use of counterfeit medications, the reasons driving their use, and the strategies enacted to contain this phenomenon.MethodsA systematic scoping review of the literature regarding counterfeit PDE5i was carried between January and June 2021, then updated in August 2021.Main Outcome MeasureWe primarily aimed to clarify the main drivers for counterfeit PDE5i use, the health risks associated, and the currently available strategies to fight counterfeiters.ResultsOne hundred thirty-one records were considered for the present scoping review. Production of fake PDE5i is highly lucrative and the lacking awareness of the potential health risks makes it a largely exploitable market by counterfeiters. Adulteration with other drugs, microbial contamination and unreliable dosages make counterfeit medications a cause of worry also outside of the sexual medicine scope. Several laboratory techniques have been devised to identify and quantify the presence of other compounds in counterfeit medications. Strategies aimed at improving awareness, providing antitampering packaging and producing non-falsifiable products, such as the orodispersible formulations, are also described.Clinical implicationsImproving our understanding of the PDE5i counterfeit phenomenon can be helpful to promote awareness of this issue and to improve patient care.Strengths & LimitationsDespite the systematic approach, few clinical studies were retrieved, and data concerning the prevalence of counterfeit PDE5i use is not available on a global scale.ConclusionThe counterfeit phenomenon is a steadily growing issue, with PDE5i being the most counterfeited medication with potentially large harmful effects on unaware consumers.Sansone A, Cuzin B, and Jannini EA. Facing Counterfeit Medications in Sexual Medicine. A Systematic Scoping Review on Social Strategies and Technological Solutions. Sex Med 2021;9:100437.

Phosphodiesterase type 5 inhibitors use and risk of colorectal cancer: a systematic review and meta-analysis.

Experimental evidence has revealed that phosphodiesterase five inhibitors (PDE5is) increase epithelial barrier function and suppress intestinal carcinogenesis. Few epidemiological studies have investigated the role of PDE5i in increasing the risk of colorectal cancer (CRC); however, these studies have proffered varying conclusions. We therefore aimed to perform a comprehensive review and meta-analysis to investigate whether PDE5i use is associated with the incidence of CRC. Databases, namely, PubMed, Scopus, Embase, and Web of Science, were used for literature search. Observational studies (published until January 31, 2021) that assessed the association of PDE5i use with CRC incidence were considered. Pooled relative risk (RR) estimates and corresponding 95% confidence intervals (CIs) were calculated using the DerSimonian-Laird random-effects model. We identified four retrospective studies that involved 965,044 participants and 3,518 CRC cases detected during a mean follow-up of 12.7years. Pooled results indicated a significantly reduced CRC risk among all PDE5i users (RR, 0.85; 95% CI, 0.76-0.95; P = 0.004, I2 = 63%). Moreover, continuous use of PDE5i was associated with a significantly reduced risk of CRC (RR, 0.63; 95% CI, 0.59-0.68; P < 0.001, I2 = 0.0%). However, the type of PDE5i exhibited no association with the risk of CRC (RR, 1.00; 95% CI, 0.98-1.02; I2 = 84.7%). Our findings suggest that continuous use of PDE5i was associated with a significantly reduced risk of CRC development. Future studies with a longitudinal design and adequate control of confounding factors are required to clarify whether a longer duration of PDE5i use alters the risk of CRC.

V12-08 MODIFIED APICAL DISSECTION AND LATERAL PROSTATIC FASCIA PRESERVATION: PRELIMINARY ANALYSIS OF THE REPRODUCIBILITY OF THE NOVEL TECHNIQUE

You have accessJournal of UrologyProstate Oncology I (Prostatectomy) (V12)1 Sep 2021V12-08 MODIFIED APICAL DISSECTION AND LATERAL PROSTATIC FASCIA PRESERVATION: PRELIMINARY ANALYSIS OF THE REPRODUCIBILITY OF THE NOVEL TECHNIQUE Bernardo Rocco, Luca Sarchi, Simone Assumma, Alessandra Cassani, Elena Morini, Filippo Turri, Cosimo De Carne, Carlo Bellorofonte, Paolo Marcangeli, Claudio Cesana, Giorgio Bozzini, Salvatore Micali, and Maria Chiara Sighinolfi Bernardo RoccoBernardo Rocco More articles by this author , Luca SarchiLuca Sarchi More articles by this author , Simone AssummaSimone Assumma More articles by this author , Alessandra CassaniAlessandra Cassani More articles by this author , Elena MoriniElena Morini More articles by this author , Filippo TurriFilippo Turri More articles by this author , Cosimo De CarneCosimo De Carne More articles by this author , Carlo BellorofonteCarlo Bellorofonte More articles by this author , Paolo MarcangeliPaolo Marcangeli More articles by this author , Claudio CesanaClaudio Cesana More articles by this author , Giorgio BozziniGiorgio Bozzini More articles by this author , Salvatore MicaliSalvatore Micali More articles by this author , and Maria Chiara SighinolfiMaria Chiara Sighinolfi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002093.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Novel modified technique (mod-RALP) seems to improve functional outcomes in terms of continence and potency. Whereas these clear advantages, the issue of reproducibility of the technique has not been investigated. Moscovas et al reported their series of 104 patients (first 18 cases as a part of LC process); we aim to analyze the mod-RALP reproducibility with insights on safety and efficacy compared to standard approach. METHODS: A prospective study performed since October 2020, 20 patients with cT2 PCa undergo a mod-RALP (low-intermediate D’Amico risk group). PND was performed according to MSK nomogram, NS strategy according to PRECE tool. A single surgeon performed all procedures (BR). First transperitoneal anterior trocar placement (6 port). After bladder detachment and periprostatic fat excision, anterior bladder neck is opened followed by posterior bladder neck dissection. After seminal vesicle excision, the dissection goes caudally, in the posterior plane. The 0° camera allows blunt dissection toward the apex and lateral aspects of the prostate, avoiding energy use and sharp traumatic incisions. When a NS is planned, after posterior release, a plane medial to the lateral prostatic fascia is developed, leaving the NVBs unseen lateral to the fascial opening at the base. The anterior dissection continues underneath the puboprostatic ligament, preserving apical anatomy. Santorini plexus is controlled by a running barbed suture after the apical dissection and before the urethral division. Endpoints are time from bladder neck incision to urethral section; PSM rate stratified by pT, continence and potency at 30 days. RESULTS: Mod-RALP had no complication. Median time from bladder neck to urethral section was 42 min (DS 9). 16 patients had organ confined disease pT2 with no PSM, (25% had an apical localization of PCa), 1 pT3a, 1 pT3b and 1 pT4. As far as early continence and potency recovery all patients were continent at 30 days (safety pad in 2). All pre-op potent patients (IIEF 5>21) restored an erection sufficient for intercourse with the use of PDE-5i. CONCLUSIONS: From our preliminary experience, mod-RALP is reproducible without compromising oncological safety and operatory time. To our knowledge, this is the first case series testing the transferability of mod-RALP to an independent center. The careful dissection with maximal preservation of the apex enables a recovery of continence in all patients. Despite the single and high-volume surgeon characteristic of our series, the use of the mod-RALP should be furtherly encouraged. Source of Funding: none © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1026-e1026 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bernardo Rocco More articles by this author Luca Sarchi More articles by this author Simone Assumma More articles by this author Alessandra Cassani More articles by this author Elena Morini More articles by this author Filippo Turri More articles by this author Cosimo De Carne More articles by this author Carlo Bellorofonte More articles by this author Paolo Marcangeli More articles by this author Claudio Cesana More articles by this author Giorgio Bozzini More articles by this author Salvatore Micali More articles by this author Maria Chiara Sighinolfi More articles by this author Expand All Advertisement Loading ...

Low-intensity extracorporeal shock wave therapy for Peyronie's disease: a single-center experience.

The aim of this article is to assess the outcomes of a low-intensity extracorporeal shock wave therapy (LiESWT) protocol for the treatment of Peyronie's disease (PD). Patients treated for PD were prospectively recorded, and data were retrospectively reviewed. Age, characteristics of fibrous plaques, concomitant treatments, International Index of Erectile Function (IIEF-5), Lue score, and pain score on Likert scale were collected. Patients in acute phase of PD and an angulation of <40° were included. The protocol consisted of 6 weekly sessions of 4000 pulses each, applied from different directions, with a maximal power of 20 W and 8 Hz frequency. We included 39 patients (median age: 56.8 years, interquartile range [IQR]: 35.8–62.2 years). The median number of sessions received per patient was 7.2. After treatment, the median Lue score decreased from 6.8 initially to 3.3 (P = 0.003), the median Likert pain score dropped from 1.8 to 0.7 (P = 0.004), the median plaque size was reduced from 2 cm to 1.2 cm (P = 0.08), and the median penile curvature diminished from 31° to 17° (P = 0.07). On univariate and multivariate analysis, the only predictors of success were younger age (odds ratio [OR] = 0.95, P = 0.03 and OR = 0.91, P = 0.04, respectively) and concomitant use of phosphodiesterase-5 inhibitors (PDE5i; OR = 0.92, P = 0.02 and OR = 0.93, P = 0.01, respectively). LiESWT had a favorable impact on Lue score and notably penile pain, curvature, plaque size, and erectile function in patients treated for PD during the early inflammatory phase, with no side effects. Younger age and concomitant use of PDE5i were the only success predictors.

Phosphodiesterase-5 Inhibitors and Outcomes During Left Ventricular Assist Device Support: A Systematic Review and Meta-Analysis

BackgroundPhosphodiesterase-5 inhibitors (PDE5i) have been used to treat pulmonary hypertension and right ventricular failure in patients with left ventricular assist devices (LVAD). The effects of PDE5i on post-LVAD outcomes including hemocompatibility-related adverse events are not well-established. This systematic review and meta-analysis aims to evaluate the effects of PDE5i on post-LVAD outcomes. Methods and ResultsA comprehensive literature search was conducted using Pubmed and Embase databases from inception through November 25, 2020, to compare post-LVAD outcomes in patients with or without PDE5i use. Pooled odds ratio (OR) with 95% confidence intervals (CI) and I2 statistic were calculated. Thirteen observational studies were included in this analysis. The use of PDE5i was not significantly associated with lower postoperative right ventricular failure (OR 0.38, 95% CI 0.02–5.96, P = .41). There was no significant association between PDE5i and gastrointestinal bleeding (OR 1.23, 95% CI 0.76–1.98, P = .2), overall stroke (OR 0.60, 95% CI 0.21–1.68, P = .17), ischemic stroke (OR 0.61, 95% CI 0.09–4.07, P = .38), or pump thrombosis (OR 0.71, 95% CI 0.14–3.54, P = .46). ConclusionsOur meta-analysis showed no significant association between PDE5i and post-LVAD right ventricular failure. Despite the antiplatelet effects of PDE5i, there was no significant association between PDE5i and gastrointestinal bleeding, overall stroke, ischemic stroke, or pump thrombosis. Randomized controlled studies are warranted to evaluate the net benefits or harms of PDE5i in the LVAD population.