Use Of Phosphodiesterase Inhibitors Research Articles

The Role of 5-Phosphodiesterase Inhibitors (PDE-5I) in Current Benign Prostatic Hyperplasia Treatment: A Narrative Review

Introduction: 5-phosphodiesterase inhibitors (PDE-5I) have been investigated as a treatment for urinary dysfunction for almost a decade. The general perception is that they play a significant role in managing lower urinary tract symptoms (LUTS), particularly those associated with benign prostatic hyperplasia (BPH). However, the specific biochemical processes by which PDE-5I repairs urinary function are still poorly understood and there is little instrumental evidence of significant improvement in urinary symptoms. Therefore, we explore the role of 5-phosphodiesterase inhibitors (PDE-5I) as complementary to the conventional treatment of symptomatic BPH; we provide the suggested biological procedures involved in the association between PDE-5 inhibitor use and improvement in LUTS; and we propose new approaches to this topic. Material and Methods: A systematic search for clinical trials, experimental studies, and systematic reviews was performed in electronic libraries (PubMed, EMBASE, Scopus) using the terms “benign prostate hypertrophy”, “benign prostate hyperplasia”, “lower urinary tract symptoms”, “storage symptoms”, “voiding symptoms”, “bladder outlet obstruction” and the keywords “mechanism of action”, “synergy”, “PDE-5 inhibitor”, “alpha1-adrenergic antagonist”, “5-alpha-reductase inhibitors” in various combinations. There was no restriction on publication date. Results: To date, only a few randomized studies have been published in which the effect of the combination of a conventional drug for the treatment of symptomatic BPH and a PDE-5I was investigated. Almost all showed significant improvement in IPSS and QoL. Some studies showed significant improvements in maximum urine flow (Qmax) and postvoiding residual volume (PVR) with combination therapy compared with a single agent alone. Conclusions: PDE-5I seems effective in relieving symptoms of some BPH patients when administered as complementary to agents currently used to treat BPH. However, the mechanism of action of PDE-5 inhibitors in LUTS remains poorly understood and it is difficult to determine the specific subset of BPH patients who will benefit from the combination of PDE-5 inhibitors with the current treatment. Well-designed, sufficiently informative comparative studies focusing on specific target group profiles (age, urogenital parameters) are needed to define new therapeutic options.

Non-arteritic anterior ischemic optic neuropathy in Black patients

Prior studies have shown that non-arteritic anterior ischemic optic neuropathy (NAION) is uncommon in persons of Black race compared to those of White race, but the reasons behind this discrepancy remain unknown. Our goal was to analyze the systemic and ocular features of Black NAION patients compared to White patients. Retrospective cross-sectional study METHODS: Self-reported race was collected from all NAION patients seen between 2014-2022 from a single US neuro-ophthalmology service. All Black NAION patients and a randomly selected sample of White NAION patients were included. We collected information on hypertension, hyperlipidemia, diabetes mellitus, hypothyroidism, obesity, ischemic heart disease, atrial fibrillation, pacemaker insertion, chronic kidney disease, dialysis, anemia, obstructive sleep apnea, deep vein thrombosis, stroke, use of phosphodiesterase inhibitors, and smoking status. We reviewed color fundus photographs and optic nerve OCT images to assess cup-to-disc ratio and document the presence of optic disc drusen. Counterfactual random forest was used to estimate associations for each characteristic of interest by race controlling for the other exposures. We included 32 Black NAION patients (mean age 57 ± 11 years, 38% men) and 69 of 432 White patients (mean age 57 ± 15 years, 59% men). Time between NAION onset and neuro-ophthalmic examination was significantly longer in Black patients (1.5 to <3 months: OR 4.07, P = 0.03; 6 to <12 months: OR 6.05, P = 0.007). Chronic kidney disease (OR 7.53, P = 0.003) and hemodialysis (OR 13.69, P = 0.02) were significantly more frequent in Black patients. No significant differences in cup-to-disc ratio were present (0.15 to <0.25: OR 2.83, P = 0.09; 0.25 to <0.35: OR 0.56, P = 0.46; ≥0.35: OR 0.66, P = 0.44). Referral delay occurs in Black patients with NAION, likely due to its relative rarity and concern for alternate diagnoses. Black NAION patients were substantially more likely to have chronic kidney disease and be on dialysis than White patients. Despite known racial differences in cup-to-disc ratio, we found no difference between Black and White NAION patients, suggesting that the underlying proposed compartment mechanism is the same between races.

The Effect of Chronic Treatment with the Inhibitor of Phosphodiesterase 5 (PDE5), Sildenafil, in Combination with L-DOPA on Asymmetric Behavior and Monoamine Catabolism in the Striatum and Substantia Nigra of Unilaterally 6-OHDA-Lesioned Rats.

The use of phosphodiesterase inhibitors in the treatment of Parkinson's disease is currently widely discussed. The study aimed to investigate the impact of acute and chronic treatment with the phosphodiesterase 5 inhibitor, sildenafil, at low and moderate doses of 2 mg/kg and 6 mg/kg, and L-DOPA (12.5 mg/kg), alone or in combination, on asymmetric behavior and dopamine (DA) and serotonin metabolism in the striatum and substantia nigra of unilaterally 6-OHDA-lesioned rats. Acute administration of sildenafil at both tested doses jointly with L-DOPA significantly increased the number of contralateral rotations during a 2 h measurement compared to L-DOPA alone. The effect of a lower dose of sildenafil combined with L-DOPA was much greater in the second hour of measurement. However, the acute combined administration of a higher dose of sildenafil with L-DOPA resulted in an immediate and much stronger increase in the number of contralateral rotations compared to L-DOPA alone, already visible in the first hour of measurement. Interestingly, the chronic combined administration of 2 mg/kg of sildenafil and L-DOPA significantly reduced the number of contralateral rotations, especially during the first hour of measurement, compared to the long-term treatment with L-DOPA alone. Such an effect was not observed after the long-term combined treatment of a higher dose of sildenafil and L-DOPA compared to L-DOPA alone. The concentration of DA in the ipsilateral striatum and substantia nigra after the last combined chronic dose of sildenafil (2 or 6 mg/kg) and L-DOPA (12.5 mg/kg) was significantly higher than after L-DOPA alone. In spite of much stronger increases in the DA concentration in the ipsilateral striatum and substantia nigra, the number of contralateral rotations was reduced in the group of rats treated with the combination of 2 mg/kg sildenafil and L-DOPA compared to the group receiving L-DOPA alone. Moreover, the combined treatment with a low dose of sildenafil and L-DOPA had an opposite effect on DA catabolism, as assessed by DOPAC/DA and HVA/DA indexes, and these indexes were reduced in the ipsilateral striatum but increased in the contralateral striatum and substantia nigra compared to the treatment with L-DOPA alone. The results of the present study show that the addition of a low dose of a PDE5 inhibitor to the standard L-DOPA therapy differently modulates rotational behavior, the tissue DA concentration and its catabolism in the striatum and substantia nigra.

Phosphodiesterase-5 inhibitors and hearing impairment: a disproportionality analysis using the US food and drug administration adverse event reporting system

ABSTRACT Background This study aimed to investigate the association between phosphodiesterase-5 inhibitors (PDE-5i) and hearing impairment adverse events (HIAEs) while providing an overview of the characteristics of drug-related HIAEs. Research design and methods We conducted a detailed pharmacovigilance analysis using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, covering 2004 to 2022. By calculating the reporting odds ratio (ROR) and the information component (IC), we identified signals that indicate the association between PDE-5i use and HIAEs. Results Among the 191,398 reports related to PDE-5i, we identified 2,608 cases of HIAEs. Signals were observed for both PDE-5i monotherapy and polytherapy, indicating combinations of drugs. Avanafil exhibited the strongest signal (ROR: 4.35, 95% CI: 2.56–7.41, IC: 2.09, 95% CI: 0.10–3.51), while vardenafil showed the weakest signal (ROR: 2.69, 95% CI: 2.21–3.28, IC: 1.14, 95% CI: 0.74–2.04). Sildenafil had the highest reported cases (ROR: 3.03, 95% CI: 2.82–3.24, IC: 1.57, 95% CI: 1.34–1.80). Conclusion These findings highlight a significant correlation between PDE-5i use and HIAEs, emphasizing the need for careful evaluation in clinical practice and providing appropriate guidance to patients before initiating treatment.

Retrospective analysis of the efficacy of low-intensity extracorporeal shock wave therapy on young and middle-aged patients with erectile dysfunction responsive to PDE5Is: reducing the use of PDE5Is.

Low-intensity extracorporeal shock wave therapy (Li-ESWT) is a new method for treating erectile dysfunction (ED), but there are no standards yet for its indications. The study aimed to suggest the early clinical efficacy of Li-ESWT and explore its related factors in young and middle-aged patients with ED who responded to phosphodiesterase type 5 Inhibitors (PDE5Is). Data from 61 patients with ED who had previously responded to oral PDE5Is and subsequently underwent Li-ESWT were collected. This included information on age, body mass index, total testicular volume, sex hormones, as well as IIEF-EF scores before treatment and at 1, 3, and 6months after treatment. The treatment regimen involves a weekly session for four consecutive weeks, with each session administering 5000 shock wave pulses. Linear regression analysis was utilized to identify factors associated with the efficacy of Li-ESWT treatment. Additionally, the improvement in different severity groups of ED before and after treatment, along with their IIEF-EF scores, was compared. Li-ESWT was more targeted and effective for young and middle-aged patients with erectile dysfunction who responded to PDE5Is. The age of enrolled patients ranges from 22 to 53years old, and the IIEF-EF scores at 1month, 3months, and 6months after treatment were compared to baseline for efficacy assessment, showing significant improvements (P < .0001) in all instances. Linear regression analysis using baseline data revealed predictive factors associated with treatment efficacy: treatment efficacy was negatively correlated with baseline IIEF-EF scores (t = -2.599, P = .013) and positively correlated with baseline LH levels (t = 2.170, P = .036). Given the considerable cost of Li-ESWT treatment and the emphasis on treatment continuity, we hope to identify the most suitable candidates for Li-ESWT therapy, thereby optimizing its application. Our findings provide a better solution for nonelderly ED patients who are responsive to PDE5Is. This study was limited by our sample size and follow-up time. After 3months of Li-ESWT, the IIEF-EF score gradually stabilizes and short-term maintenance of PDE5Is medication increases the responsiveness to shock wave therapy.

The use of phosphodiesterase inhibitors in the treatment of female sexual dysfunction: scoping review.

The purpose of this study was to analyze the available evidence regarding the efficacy of iPDE5 in the treatment of female sexual dysfunction (FSD). A comprehensive literature search was conducted in March 2023 through the main scientific databases. A total of 53 articles were identified, out of which, 6 met the predefined inclusion criteria. All of these were randomized controlled trials. Among the included studies, 4 demonstrated the effectiveness of sildenafil in improving sexual response and addressing FSD, while 2 studies failed to establish its efficacy in this context. Overall, the efficacy of sildenafil in the treatment of FSD remains controversial and inconclusive based on the available evidence. Further research is necessary to clarify the therapeutic potential of iPDE5 in addressing FSD and to better understand the factors that influence treatment outcomes.

Proceedings of PRINCETON IV: PDE5 inhibitors and cardiac health symposium.

Prior consensus meetings have addressed the relationship between phosphodiesterase type 5 (PDE5) inhibition and cardiac health. Given significant accumulation of new data in the past decade, a fourth consensus conference on this topic was convened in Pasadena, California, on March 10 and 11, 2023. Our meeting aimed to update existing knowledge, assess current guidelines, and make recommendations for future research and practice in this area. An expert panel reviewed existing research and clinical practice guidelines. Key findings and clinical recommendations are the following: First, erectile dysfunction (ED) is a risk marker and enhancer for cardiovascular (CV) disease. For men with ED and intermediate levels of CV risk, coronary artery calcium (CAC) computed tomography should be considered in addition to previous management algorithms. Second, sexual activity is generally safe for men with ED, although stress testing should still be considered for men with reduced exercise tolerance or ischemia. Third, the safety of PDE5 inhibitor use with concomitant medications was reviewed in depth, particularly concomitant use with nitrates or alpha-blockers. With rare exceptions, PDE5 inhibitors can be safely used in men being treated for hypertension, lower urinary tract symptoms and other common male disorders. Fourth, for men unresponsive to oral therapy or with absolute contraindications for PDE5 inhibitor administration, multiple treatment options can be selected. These were reviewed in depth with clinical recommendations. Fifth, evidence from retrospective studies points strongly toward cardioprotective effects of chronic PDE5-inhibitor use in men. Decreased rates of adverse cardiac outcomes in men taking PDE-5 inhibitors has been consistently reported from multiple studies. Sixth, recommendations were made regarding over-the-counter access and potential risks of dietary supplement adulteration. Seventh, although limited data exist in women, PDE5 inhibitors are generally safe and are being tested for use in multiple new indications. Studies support the overall cardiovascular safety of the PDE5 inhibitors. New indications and applications were reviewed in depth.

Phosphodiesterase-5 Inhibitors and Dementia Risk: A Real-World Study.

Biological and scarce epidemiological evidence suggested that phosphodiesterase-5 inhibitors (PDE5i) might reduce dementia risk. We aimed to examine the association between PDE5i and dementia using real-world data. Two retrospective cohorts within the database of Clalit, the largest healthcare provider in Israel (2005-2023), were studied. The first cohort included new daily users, older than 50 years of age, of low-dose tadalafil, prescribed for benign prostatic hypertrophy (BPH), propensity-score matched to new-users of alpha-1 blockers, and analyzed using 2-year lag time. The second cohort included patients with erectile dysfunction, with/without any PDE5i treatment, using time-dependent analysis. Individuals in the cohorts were followed through May 2023 for the occurrence of dementia. The first cohort included 5,204 tadalafil initiators propensity-score matched to 18,565 alpha-1 blockers initiators. There was no association between tadalafil use and dementia risk, HR = 0.99 (95% CI: 0.88-1.12), p = 0.927. Similar results were obtained in a competing risk analysis, and in a sensitivity analysis in which we restricted the cohort to patients older than 60 years at cohort entry. The second cohort of 133,336 patients with erectile dysfunction included new users and nonusers of any PDE5i. In a mean follow-up of 7.9 years, 8,631 patients were newly diagnosed with dementia. In a time-dependent multivariable analysis, PDE5i use was not associated with reduced dementia risk, HR = 0.95 (95% CI: 0.86-1.04). Results were not changed in sensitivity analyses (patients older than 60 years or stratification by PDE5i type). This study suggests that the use of PDE5 inhibitors is not associated with decreased risk of dementia.

Phosphodiesterase-5 inhibitors use and the risk of alzheimer's disease: a systematic review and meta-analysis

BackgroundThe management of Alzheimer's disease (AD) poses considerable challenges, necessitating the pursuit of innovative therapeutic approaches. Recent research has spotlighted the promising role of phosphodiesterase type 5 inhibitors (PDE5Is) in reducing the prevalence of AD, utilizing their vasodilatory properties to suggest a potential neuroprotective effect. This meta-analysis and systematic review aims to assess the relationship between the use of PDE5Is and the risk of AD.MethodsA detailed examination was carried out across several electronic databases till March 2024, including PubMed, Web of Science, Scopus, CENTRAL, and Embase. The focus was on identifying studies that compare the occurrence of AD among PDE5I users vs non-users. Through a random-effects model, pooled hazard ratios (HRs) were calculated, in alignment with guidelines from the Cochrane Handbook for Systematic Reviews and Meta-Analysis and the PRISMA standards.ResultsThis analysis included six studies, cumulating a participant count of 8,337,313, involving individuals treated with sildenafil, tadalafil, and vardenafil, against a control group undergoing other or no treatments. The cumulative HR for AD risk among PDE5I users versus the control group was 0.53 (95% CI: 0.32–0.86, p = 0.008), signaling a markedly reduced likelihood of AD development in the PDE5I group. Particularly, sildenafil usage showed a significant risk reduction (HR: 0.46, 95% CI: 0.31–0.70, p < 0.001), while findings for tadalafil and vardenafil were not significant. Test of subgroup differences found no difference between male and female participants in the risk of AD.ConclusionsOur findings suggest that the use of PDE5Is is associated with a reduced risk of AD, highlighting its potential as a protective agent against neurodegenerative diseases. Given the very low quality of evidence and the heterogeneity among the included studies, further high-quality research is warranted to confirm these findings and elucidate the underlying mechanisms. Register number PROSPERO 2024: CRD42024522197.

PDE5 inhibition mitigates heart failure in hyperlipidemia

PDE5 inhibitors was reported to play a protective role in both regulating lipid metabolism and reducing heart failure (HF). This study aimed to clarify the effectiveness of PDE5 inhibitors against hyperlipidemia-related HF by combining evidence from population-based study and animal models. The nationwide cohort study found that post-diagnostic use of PDE5 inhibitors was associated with a significantly lower risk of HF compared with patients who used alprostadil, especially among individuals with hyperlipidemia (adjusted HR = 0.56, 95% CI = 0.40–0.78). In animal models, sildenafil significantly recovered the cardiac structure and function induced by AAB surgery, as well as reversed liver dysfunction and ameliorated hyperlipidemia induced by HFD via reducing the level of ALT, AST and serum lipids. Lipidomic analysis identified four lipid metabolites involved in sildenafil administration, including FA 16:3, LPC O-18:1, DG24:0_18:0 and SE28:1/20:4. This study revealed the protective effect of PDE5 inhibitors against HF in hyperlipidemia, indicating the potential of being repurposed as an adjuvant for HF prevention in patients with hyperlipidemia if these findings can be further confirmed in clinical trials.

Nonarteritic Anterior Ischemic Optic Neuropathy After Recreational PDE5 Inhibitor Use in a Healthy Patient: More Evidence for Causation.

Nonarteritic Anterior Ischemic Optic Neuropathy After Recreational PDE5 Inhibitor Use in a Healthy Patient: More Evidence for Causation.

Phosphodiesterase-5 Inhibitor Use Is Associated with a 60–61% Relative Decrease in the Rate of Parkinson’s Disease: A Cohort Study Supporting the Need for a Phase Three Clinical Trial (P11-9.003)

Phosphodiesterase-5 Inhibitor Use Is Associated with a 60–61% Relative Decrease in the Rate of Parkinson’s Disease: A Cohort Study Supporting the Need for a Phase Three Clinical Trial (P11-9.003)

Phosphodiesterase-5 Inhibitor Use Is Associated with a 56–71% Relative Decrease in the Rate of Ischemic Stroke: A Cohort Study Supporting the Need for a Phase Three Clinical Trial (P3-5.016)

Phosphodiesterase-5 Inhibitor Use Is Associated with a 56–71% Relative Decrease in the Rate of Ischemic Stroke: A Cohort Study Supporting the Need for a Phase Three Clinical Trial (P3-5.016)

Impact of low-intensity extracorporeal shockwave therapy on vascular parameters and sexual function in patients with arteriogenic erectile dysfunction.

Previous published studies have shown an improvement of penile hemodynamic parameters after low-intensity extracorporeal shockwave therapy (Li-ESWT). However, the clinical significance of these findings remains unclear, and definitive selection criteria for Li-ESWT based on preexisting comorbidities have yet to be established. This was an observational study of 113 patients with ED, evaluated between January 2019 and December 2021 in Andrology Unit at the Department of Urology and Renal Transplantation, University of Foggia (Foggia, Italy). Penile dynamic Doppler was performed to evaluate vascular parameters and 5-item version of the International Index of Erectile Dysfunction (IIEF-5) questionnaire was administered to assess the severity of ED. This was repeated 1 month after treatment. Patients with a peak systolic velocity (PSV) <30 cm s -1 were considered eligible for Li-ESWT. Our protocol consisted of 8 weekly sessions with 1500 strokes distributed in 5 different locations along the penis. After treatment, a significant mean (±standard deviation [s.d.]) PSV increase of 5.0 (±3.4) cm s -1 was recorded and 52/113 (46.0%) patients reached a PSV >30 cm s -1 at posttherapeutic penile dynamic Doppler. A clinically significant IIEF-5 score improvement was observed in 7 patients, 21 patients, and 2 patients with mild-to-moderate, moderate, and severe pretreatment ED, respectively. No different outcomes were assessed based on smoking habits, previous pelvic surgery, or use of oral phosphodiesterase-5 inhibitor (PDE5i). On the other side, only 1 (6.7%) in 15 patients with diabetes mellitus showed an IIEF-5 score improvement after Li-ESWT. Shockwave treatment determined a significant increase in PSV and correlated IIEF-5 improvement in ED patients. This advantage seemed particularly evident for moderate ED and was not affected by smoking habits, previous pelvic surgery, and use of PDE5i. Conversely, diabetic patients did not benefit from the treatment.

(030) Hand Held, Self-Applicable Radio Frequency Device for the Treatment of Erectile Dysfunction. A Pilot Study with 6 Months Follow-Up

Abstract Introduction Collagen is an essential component of the structures involved in the erectile mechanism. Radiofrequency (RF) energy has been shown to renew and restore the spatial structural arrangement of collagen fibers and may improve erectile function of men suffering from erectile dysfunction (ED). Objective To assess the feasibility, safety, and efficacy of low-intensity radiofrequency (RF) therapy in men with ED. Methods Men with moderate &amp; mild to moderate ED, with or without the use of PDE5-inhibitors were included. After instructions, each patient treated himself with the radiofrequency device (Vertica®), applying his selected individual RF intensity. Patients underwent, according to the protocol, 12 sessions of 30-minute treatments over 2 months. Patients were evaluated at baseline, 1, 3 and 6 months after treatment using validated questionnaires; International Index of Erectile Function (Full IIEF), IIEF-EF, and erection Hardness score (EHS), satisfaction (EDITS, BSW), and disease-specific quality and quality of life (QEQ, SQOL). In each session, patients filled safety and side-effect questions (pain, fever, burning, discomfort, urinary disorders). The Wilcoxon signed ranks test and the Marginal Homogeneity test were used for statistical processing. Results Twenty-seven out of 28 men treated, were available for 6 months follow-up, mean age 59.2±9.7. The mean ED duration was 41.2±29 months. Mean baseline IIEF-EF was 16.8±1 and improved significantly to 24.8±1.6, 24.3±1.8, and 24.2±2.08 at 1, 3 and 6 months respectively (p&amp;lt;0.001). The Minimal Clinical Important Difference (MCID) criteria were met by 25/28 (89%) at 1-month follow-up and 20/27(74%) at 6-month follow-up (p&amp;lt;0.001). A statistically and clinically significant improvement was demonstrated in the Full IIEF and EHS scores at baseline and during follow-up. No correlation was found between IIEF improvement and the age of the patients. Borderline significance (p=0.05) was found between the duration of ED and IIEF-EF improvement. No side effects were reported and participants rated the device as very comfortable and easy to operate. Conclusions The novel radiofrequency, home-use device for the treatment of ED shows promising results and the potential to improve erectile function. In this study, it was feasible and safe. Further high-quality randomized controlled trials are needed to determine the long-term efficacy of the treatment. Disclosure Yes, this is sponsored by industry/sponsor: Ohhmed, Israel. Clarification: No industry support in study design or execution. Any of the authors act as a consultant, employee or shareholder of an industry for: Ohhmed, Freya, Besins, Verility.

Medical management of benign prostatic hyperplasia.

Medical management of benign prostatic hyperplasia (BPH) has progressed gradually in recent years and remains the starting point for most symptomatic patients seeking treatment. Beyond well-known alpha-blockers and 5-alpha reductase inhibitors, there is growing evidence for the use of phosphodiesterase-5 inhibitors and beta-3 agonists in managing the condition, which may afford additional relief of "bothersome" symptoms in some patients. This review details contemporary medical management of BPH with an emphasis on the indications for certain classes of pharmacotherapy and their relative benefits and side effects. Surgical and procedural treatment of BPH is covered in a separate review.

(222) Simultaneous Inflatable Penile Prosthesis and Adjustable Male Sling: A Step-by-Step Surgical Technique

Abstract Introduction Erectile dysfunction (ED) and urinary incontinence (UI) are common complications following radical prostatectomy (1). At twenty-four months post-surgery, approximately 43% of men experience some degree of ED, while UI affects around 15% of patients between twelve to twenty-four months (2, 3). Notably, nearly 20% of patients experience both ED and UI complications (4). Initial conservative management strategies include the use of PDE-5 inhibitors, intercavernosal injections, or a vacuum erectile device for ED and pelvic floor muscle training for UI (5). However, symptoms that persist or worsen beyond six months can be considered for surgical intervention (6). Surgical options include penile prosthesis implantation for ED and diverse techniques such as the Artificial Urinary Sphincter (AUS) or adjustable male urethral sling, depending on symptom severity, for UI management. Limited evidence suggests that a simultaneous surgical approach addressing both conditions can be a cost-effective and a safe alternative to separate surgeries (7, 8). Objective In this context, the objective of this video presentation is to illustrate a detailed, step-by-step technique for the simultaneous implantation of an inflatable penile prosthesis (IPP) and an adjustable male sling (AMS), while also discussing its feasibility, safety, and functional outcomes. Methods The combined IPP and AMS surgery is a safe, viable, and cost-effective option for patients who need to address both ED and UI. Rhee (2005) initially described the concurrent placement of a penile prosthesis (PP) and male sling (MS) in a series of four post-prostatectomy patients. Results The results demonstrated successful restoration of erections and complete continence in all patients, with no postoperative complications. Our previous systematic review, comparing the outcomes of simultaneous surgical placement of PP and MS versus PP and artificial urethral sphincter (AUS), found no clinically significant differences in outcomes between the two groups (Raheem 2021). Therefore, the simultaneous placement of IPP and AMS should be considered an option for patients, as it shows comparable effectiveness to other concurrent surgical interventions. Dual implantation of PP and male sling have also demonstrated cost savings of approximately $9,000 for patients, further enhancing its advantages in managing both ED and UI (Gorbatiy 2010). Ultimately, a collaborative discussion between patients and their urologist is crucial in determining the most suitable approach for patient individual needs. Conclusions The simultaneous surgical placement of an inflatable penile prosthesis (IPP) and adjustable male sling (AMS) presents a favorable and viable solution for managing erectile dysfunction (ED) and urinary incontinence (UI) in patients who exhibit an inadequate response to conservative management following prostatectomy. Disclosure No.

Do Phosphodiesterase Type 5 Inhibitors Increase the Risk of Biochemical Recurrence After Radical Prostatectomy?

There have been conflicting studies on the association between phosphodiesterase type 5 inhibitor (PDE5i) use and biochemical recurrence (BCR) following radical prostatectomy (RP). Our aim was to determine whether PDE5i drug exposure after RP increases the risk of BCR in patients undergoing RP. An institutional database of prostate cancer patients treated between January 2009 and December 2020 was reviewed. BCR was defined as 2 PSA measurements greater than 0.1 ng/mL. PDE5i exposure was defined using a 0 to 3 scale, with 0 representing never use, 1 sometimes use, 2 regularly use, and 3 routinely use. The risk of BCR with any PDE5i exposure, the quantity of exposure, and the duration of PDE5i exposure were assessed by multivariable Cox proportional hazards models. The sample size included 4630 patients to be analyzed, with 776 patients having BCR. The median follow-up for patients without BCR was 27 (IQR 12, 49) months. Eighty-nine percent reported taking a PDE5i at any time during the first 12 months after RP, and 60% reported doing so for 6 or more months during the year after RP. There was no evidence of an increase in the risk of BCR associated with any PDE5i use (HR 1.05, 95% CI 0.84, 1.31, P = .7) or duration of PDE5i use in the first year (HR 0.98 per 1 month duration, 95% CI 0.96, 1.00, P = .055). Baseline oncologic risk was lower in patients using PDE5i, but differences between groups were small, suggesting that residual confounding is unlikely to obscure any causal association with BCR. Prescription of PDE5i to men after RP can be based exclusively on quality of life considerations. Patients receiving PDE5is can be reassured that their use does not increase the risk of BCR.

Safety and efficacy of phosphodiesterase-5 (PDE-5) inhibitors in fetal growth restriction: a systematic literature review and meta-analysis.

Introduction: Fetal growth restriction (FGR) is associated with a higher risk of perinatal morbidity and mortality, as well as long-term health issues in newborns. Currently, there is no effective medicine for FGR. Phosphodiesterase-5 (PDE-5) inhibitors have been shown in pre-clinical studies to improve FGR. This study aimed to evaluate the latest evidence about the clinical outcomes and safety of PDE-5 inhibitors for the management of FGR. Methods: Eight databases (PubMed, Embase, Medline, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Database and WangFang Database) were searched for English and Chinese articles published from the database inception to December 2023. Randomized controlled trials (RCTs) reporting the use of PDE-5 inhibitors in FGR were included. The quality of the RCTs was assessed using the Cochrane Risk of Bias Tool. Odds ratio and mean difference (MD) (95% confidence intervals) were pooled for meta-analysis. Results: From 253 retrieved publications, 16 studies involving 1,492 pregnant women met the inclusion criteria. Only sildenafil (15 RCTs) and tadalafil (1 RCT) were studied for FGR. Compared with the control group (placebo, no treatment, or other medication therapies), sildenafil increased birth weight, pregnancy prolongation and umbilical artery pulsatility indices. However, it also increased the risk of pulmonary hypertension in newborns, as well as headache and flushing/rash in mothers. There were no significant differences in gestation age, perinatal mortality or major neonatal morbidity, stillbirth, neonate death, infants admitted to neonatal intensive care unit, intraventricular hemorrhage and necrotizing enterocolitis in infants, as well as pregnancy hypertension and gastrointestinal side effects in mothers between the treatment and the control groups. Discussion: Sildenafil was the most investigated PDE-5 inhibitors for FGR. Current evidence suggests that sildenafil can improve birth weight and duration of pregnancy but at the same time increase the risk of neonatal pulmonary hypertension. It remains uncertain whether the benefits of sildenafil in FGR outweigh the risks and further high-quality RCTs are warranted. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=325909.

Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health.

In 1999, 1 year after the approval of the first oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction (ED), the first Princeton Consensus Conference was held to address the clinical management of men with ED who also had cardiovascular disease. These issues were readdressed in the second and third conferences. In the 13years since the last Princeton Consensus Conference, the experience with PDE5 inhibitors is more robust, and recent new data have emerged regarding not only safety and drug-drug interactions, but also a potential cardioprotective effect of these drugs. In March 2023, an interdisciplinary group of scientists and practitioners met for the fourth Princeton Consensus Guidelines at the Huntington Medical Research Institutes in Pasadena, California, to readdress the cardiovascular workup of men presenting with ED as well as the approach to treatment of ED in men with known cardiovascular disease. A series of lectures from experts in the field followed by Delphi-type discussions were developed to reach consensus. Consensus was reached regarding a number of issues related to erectile dysfunction and the interaction with cardiovascular health and phosphodiesterase-5 inhibitors. An algorithm based on recent recommendations of the American College of Cardiology and American Heart Association, including the use of computed tomography coronary artery calcium scoring, was integrated into the evaluation of men presenting with ED. Additionally, the issue of nitrate use was further considered in an algorithm regarding the treatment of ED patients with coronary artery disease. Other topics included the psychological effect of ED and the benefits of treating it; the mechanism of action of the PDE5 inhibitors; drug-drug interactions; optimizing use of a PDE5 inhibitors; rare adverse events; potential cardiovascular benefits observed in recent retrospective studies; adulteration of dietary supplements with PDE5 inhibitors; the pros and cons of over-the-counter PDE5 inhibitors; non-PDE5 inhibitor therapy for ED including restorative therapies such as stem cells, platelet-rich plasma, and shock therapy; other non-PDE5 inhibitor therapies, including injection therapy and penile prostheses; the issue of safety and effectiveness of PDE5 inhibitors in women; and recommendations for future studies in the field of sexual dysfunction and PDE5 inhibitor use were discussed. Algorithms and tables were developed to help guide the clinician in dealing with the interaction of ED and cardiovascular risk and disease. Strengths include the expertise of the participants and consensus recommendations. Limitations included that participants were from the United States only for this particular meeting. The issue of the intersection between cardiovascular health and sexual health remains an important topic with new studies suggesting the cardiovascular safety of PDE5 inhibitors.