Use Of Phosphodiesterase Inhibitors Research Articles

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.

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.

A drug target for erectile dysfunction to help improve fertility, sexual activity, and wellbeing: mendelian randomisation study

ObjectiveTo investigate the association of genetically proxied (using a surrogate biomarker) inhibition of phosphodiesterase 5 (PDE5), an established drug target for erectile dysfunction, with fertility, sexual behaviour, and subjective wellbeing.DesignTwo...

Abstract 13680: Assessing the Role of Phosphodiesterase-5 Inhibitors in the Management of Left Ventricular Assist Device Patients: A Systematic Review and Meta-Analysis

Introduction: The advent of left ventricular assist device (LVAD) therapy revolutionized the management of severe heart failure. Right ventricular failure (RVF) remains a principal cause of mortality among these patients. Previous reports suggest phosphodiesterase-5 inhibitors (PDE-5is) can decrease pulmonary pressure, enhance ventricular function, and lower the risk of thrombosis and stroke. Nonetheless, certain studies present conflicting data, indicating potential increases in bleeding and mortality among patients using PDE-5is. Hypothesis: This study aimed to assess the outcomes of LVAD patients who were administered PDE-5is. Methods: A comprehensive search of PubMed/Medline, EMBASE, Cochrane, Web of Science, Scopus, and grey literature was conducted until January 2022. We included studies that directly compared outcomes of LVAD patients who used PDE-5is versus those who did not. Primary outcomes focused on postoperative RVF and all-cause mortality, while secondary outcomes included stroke, gastrointestinal bleeding, and pump thrombosis. The statistical analysis was performed using "R" statistical computing software (version 4), utilizing the metafor and meta packages. Results: Eight studies encompassing 3035 PDE-5i users and 3023 non-users were included in our analysis. PDE-5i use was not significantly associated with postoperative RVF (RR: 0.84; 95% CI 0.58-1.21, P=0.35; I2 = 83.2%). Similarly, there was no significant correlation between PDE-5i use and all-cause mortality (RR: 0.99; 95% CI 0.96-1.02, P=0.75; I2 = 0%), pump thrombosis (RR: 0.66; 95% CI 0.61-0.72, P=0.45; I2 = 0%), stroke (RR: 0.96; 95% CI 0.84-1.08, P=0.58; I2 = 0%), or gastrointestinal bleeding (RR: 1.13; 95% CI 0.77-1.67, P=0.65; I2 = 0%). Conclusions: Our analysis suggests that PDE-5i use is not associated with increased adverse outcomes such as bleeding, stroke, thrombosis, or all-cause mortality in LVAD patients. However, given the heterogeneity of the included studies and a lack of robust evidence supporting PDE-5i use, high-quality randomized controlled trials are needed to assess the potential benefits, efficacy, and safety of PDE-5is in reducing RVF, thrombosis, and all-cause mortality in LVAD patients.

Use of phosphodiesterase 5 inhibitors is not associated with ocular adverse events.

Phosphodiesterase 5 inhibitor (PDE5i) use has been linked to a number of ocular side effects, such as serous retinal detachment (SRD), retinal vascular occlusion (RVO), and ischemic optic neuropathy (ION). We investigated the risk for SRD, RVO, and ION in patients using PDE5is. We utilized the IBM MarketScan (2007-2021) Commercial and Medicare Supplemental Databases (version 2.0) for this analysis. To estimate overall events risk, Cox proportional hazard models were applied to calculate the hazard ratios (HRs) for erectile dysfunction (ED) diagnosis and the different treatments, adjusting for region, median age, obesity, diabetes mellitus, hyperlipidemia, smoking, hypertension, coronary artery disease, and sleep apnea. Additionally, the same analyses were performed to calculate the HRs for benign prostatic hyperplasia (BPH) diagnosis and the different treatments. HRs for SRD, RVO, and ION. In total, 1 938 262 men with an ED diagnosis were observed during the study period. Among them, 615 838 (31.8%) were treated with PDE5is. In total, 2 175 439 men with a BPH diagnosis were observed during the study period. Among them, 175 725 (8.1%) were treated with PDE5is. On adjusted Cox regression analysis, PDE5i use was not associated with SRD, RVO, ION, and any ocular event when compared with ED diagnosis and other ED treatments. Importantly, as the intensity of ED treatment increased, so did the risk of ocular events. In addition, PDE5i use was not associated with SRD and ION when compared with BPH diagnosis and other BPH treatments. In contrast, in patients with BPH, PDE5i use was associated with RVO (HR, 1.14; 95% CI, 1.06-1.23). Importantly, patients with BPH receiving other medical treatment (ie, 5a reductase/alpha blocker; HR, 1.11; 95% CI, 1.06-1.16) or surgical treatment (HR, 1.10; 95% CI, 1.02-1.19) had a higher risk of RVO. We did not observe any consistent association between PDE5i use and any ocular adverse events (SRD, RVO, and ION). Because we did not have access to the patients' medical records, we recorded outcome definitions using ICD-9 and ICD-10 coding. Patients using PDE5is for ED or BPH indications did not have an increased risk of ocular events, even when compared with other treatments for ED or BPH.

Use of Phosphodiesterase Inhibitors in Patients with Penile Artery Occlusion

Penile artery occlusion is a vascular condition that can lead to erectile dysfunction, significantly affecting a patient's quality of life and psychological well-being. This comprehensive review explores the epidemiology and clinical significance of penile artery occlusion, emphasizing the substantial impact it has on patients' sexual health. The theoretical framework delves into the definition of penile artery occlusion, identifies risk factors contributing to its development, discusses potential complications, and outlines current management strategies. The discussion section evaluates the use of phosphodiesterase inhibitors as a therapeutic approach in patients with penile artery occlusion, providing insights into their mechanisms of action, efficacy, and safety. The conclusion emphasizes the importance of a personalized approach to managing this condition, with phosphodiesterase inhibitors as a valuable option.

OR25-02 Hunting The Magic Bullet In Treating Male Secondary Hypogonadism Associated With Metabolic Syndrome: Results Of a Prospective Study Comparing Liraglutide Vs. Gonadotropins

Abstract Disclosure: S. La Vignera: None. R.A. Condorelli: None. A.E. Calogero: None. R. Cannarella: None. E. Greco: None. A. Aversa: None. Background: Previously, we hypothesized a role for glucagon-like peptide-1 (GLP1) analogs in the treatment of male infertility (DOI: 10.1111/andr.13015), although no studies have so far investigated this issue. Purpose: To prospectively investigate the effects of treatment with liraglutide, a GLP1 analog, on reproductive and sexual function in men with functional hypogonadism of childbearing age. Patients and Methods: 110 obese men of childbearing age (18-35 years) with functional hypogonadism were enrolled and divided into three groups based on their desire to have children. Group A consisted of men actively seeking paternity, Group B of men who did not seek paternity, and Group C of men who had already fathered a child. Group A was treated with gonadotropins [urofollitropin 150 IU three times a week and human chorionic gonadotropin (hCG) 2000 IU twice a week], Group B with liraglutide (3 mg daily), and Group C with transdermal testosterone (60 mg daily). The following endpoints were measured at enrolment and after 4 months: anthropometric and metabolic parameters, gonadotropins, total testosterone, conventional sperm parameters (Group A and B only), the score of the International Index of Erectile Function 5 Items (IIEF5), and frequency of phosphodiesterase type 5 inhibitors (PDE5i) use. Results: The groups did not differ on any of the baseline endpoints. Weight, body mass index, and waist circumference significantly decreased after treatment in Group B, but not in the other Groups. Liraglutide significantly increased LH (3.2±0.2 IU/L vs. 2.0±0.3 IU/L; p&amp;lt;0.01), FSH (2.6±0.2 IU/L vs. 1.6±0.3 IU/L; p&amp;lt;0.01), total testosterone (4.1±0.5 ng/mL vs. 1.4±0.6 ng/mL; p&amp;lt;0.05), and sex hormone-binding globulin (36.0±4.0 nmol/L vs. 14.0±3.0 nmol/L) levels from baseline, while no improvement was observed in the other Groups. Liraglutide increased sperm concentration (16±4 mil/ml vs. 6±2 mil/ml; p&amp;lt;0.05), progressive motility (34±4 % vs. 14±2 %; p&amp;lt;0.01), and morphology (10±2 % vs. 4±2 %; p&amp;lt;0.05), while treatment with gonadotropins only increased sperm progressive motility (19±2 % vs. 12±3 %; p&amp;lt;0.05) compared to baseline. The IIEF-5 score improved after liraglutide treatment (4±2 vs. 21±4; p&amp;lt;0.05), while no significant changes were observed in the other Groups. Similarly, PDE5i use decreased significantly in Group B (31%), compared with Groups A (48%) and C (45%). Conclusions: Liraglutide is an effective weight loss drug, which also improves serum gonadotropin and total testosterone levels, sperm conventional parameters, and sexual function in obese patients with functional hypogonadism seeking parenthood. This is the first study documenting the efficacy of liraglutide on the testicular function of these patients. Presentation Date: Saturday, June 17, 2023

Safety profile and signal detection of phosphodiesterase type 5 inhibitors for erectile dysfunction: a Food and Drug Administration Adverse Event Reporting System analysis.

Phosphodiesterase type 5 inhibitors (PDE5Is) are generally well tolerated but have been associated with uncommon and significant adverse events (AEs). This study aims to investigate and compare the characteristics of AEs associated with PDE5Is used for erectile dysfunction and identify any safety signals in a postmarketing surveillance database between 2010 and 2021. A descriptive analysis was conducted for all AEs reported to the Food and Drug Administration Adverse Event Reporting System for 4 PDE5Is-avanafil, sildenafil, tadalafil, and vardenafil-indicated for erectile dysfunction between January 2010 and December 2021. The frequency of the most reported AEs and outcomes were identified. A disproportionality analysis based on proportional reporting ratio (PRR) and reporting odds ratio (ROR) was conducted for the most common and clinically important AEs to identify signals to gain insights into potential differences in safety profiles. The outcome measures of the study are frequency of reported AEs and outcomes following AE. A total of 29 236 AEs were reported for PDE5Is during the study period. The most reported AE was "drug ineffective" with 7115 reports (24.3%). Eight safety signals were detected across the 4 drugs. Key signals were sexual disorders (PRR, 3.13 [95% CI, 2.69-3.65]; ROR, 3.24 [95% CI, 2.77-3.79]) and death (PRR, 3.17 [2.5-4.01]; ROR, 3.211 [2.52-4.06]) for sildenafil, priapism (PRR, 3.63 [2.11-6.24]; ROR, 3.64 [2.12-6.26]) for tadalafil, and drug administration error (PRR, 2.54 [1.84-3.52]; ROR, 2.6 [1.86-3.63]) for vardenafil. The most reported outcomes were other serious events with 6685 events (67.2%) and hospitalization with 1939 events (19.5%). The commonly reported AEs and detected signals may guide clinicians in treatment decision making for men with erectile dysfunction. This is the first comprehensive report and disproportionality analysis on all types of AEs associated with PDE5Is used for erectile dysfunction in the United States. The findings should be interpreted cautiously due to limitations in the Adverse Event Reporting System, which includes self-reports, duplicate and incomplete reports, and biases in reporting and selection. Therefore, establishing a causal relationship between the reported AEs and the use of PDE5Is is uncertain, and the data may be confounded by other medications and indications. PDE5Is demonstrate significantly increased risks of reporting certain clinically important AEs. While these events are not common, it is imperative to continually monitor PDE5I use at the levels of primary care to national surveillance to ensure safe utilization.

Evaluating the Oncological and Functional Outcomes in 167 Patients Undergoing Laparoscopic Radical Prostatectomy: Could Laparoscopy Still be a Viable Option in Suitable Patients?

Aim: To evaluate the oncological and functional outcomes of 167 patients who underwent laparoscopic radical prostatectomy (LRP). Materials and Methods: The retrospective study included 167 patients who were treated with LRP due to clinically localized prostate cancer between January 2007 and April 2012. Most of the patients were treated with the extraperitoneal approach. Preoperative evaluations included age, serum prostate-specific antigen (PSA) level, and biopsy Gleason score. Perioperative evaluations included duration of operative time and anastomosis time, blood loss (milliliter), and complications. Postoperative evaluations included length of hospital stay and catheterization time. Continence and erectile function were evaluated both pre- and postoperatively. The patients who used no pads or no more than one pad daily and the ones who had only a few urine leakages on effort or exertion were accepted as continent. Postoperative potency was defined as the ability to achieve sexual intercourse with or without the use of PDE-5 inhibitors. Results: Mean age and mean operative time were 62.4 ± 6.0 years and 220.5 ± 45.6 minutes, respectively. Mean anastomosis time was 35.6 ± 9.8 minutes. Mean serum PSA level and mean Gleason score were 17.5 ± 9.97 ng/mL and 6.16 ± 0.42, respectively. Pelvic lymphadenectomy was performed in 94 patients and nerve-sparing procedures in 61 patients. The pathological analysis revealed positive surgical margin in 35 patients (20.9%). Bilateral and unilateral nerve-sparing LRP procedures were performed in 51 (30.5%) and 10 (6%) patients, respectively. At 12 months after surgery, 3 (1.8%) patients were using 2 or more pads per day, 19 (26.4%) patients were satisfied with erection, hardness, and duration of intercourse, and 9 (12.5%) patients had an erection with insufficient hardness and duration. Conclusion: LRP is an acceptable method in localized prostate cancer due to its perioperative and early postoperative results.

Association Between Common Urologic Medications and Onset of Alzheimer’s Disease and Related Dementias in Men With Prostate Cancer Managed by Different Primary Treatment Modalities

To understand the relationship between common urologic medications phosphodiesterase-5 inhibitors (PDE5i) and anticholinergics (AC) and risk of dementia onset in men who underwent different primary treatments for prostate cancer. Patients (>50years) with prostate cancer (1998-2022) without Alzheimer's disease or related dementias were selected from Cancer of the Prostatic Strategic Urologic Research Endeavor Registry. Minimum medication use was 3months. Fine-Gray regression was performed to determine the association between medication exposure and dementia onset ≥12months after primary treatment in men matched on age, race, comorbid conditions, smoking, and type of clinical site, with competing risk of death. Among 5937 men (53% PDE5i; 14% AC), PDE5i users were younger (63 vs 70, P<.01) with less CAD, CVA, DM (all P<.01); AC users were older (68 vs 66, P<.01) with higher incidence of comorbidities (P<.01). Median months of use was 24.3 (IQR 12.1, 48.7) for PDE5i and 12.2 (IQR 6.1, 24.3) for AC users. Cumulative incidence of Alzheimer's disease or related dementias was 6.5% at 15years. PDE5i (P=.07) and AC (P=.06) were not associated with dementia regardless of primary treatment modality. In this retrospective cohort study, PDE5i and AC use do not appear independently associated with risk of dementia. Notably, our cohort was generally healthy and younger which may limit our ability to detect significance. We recommend prospective investigation into association between PDE5i and dementia and advise continued judicious stewardship of AC in older patient populations.

The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta-analysis.

Inflammatory cells within the tumour microenvironment are the driving forces behind colorectal cancer (CRC) tumourigenesis. Understanding the different pathways involved in CRC carcinogenesis paves the way for effective repurposing of drugs for cancer prevention. Emerging data from preclinical and clinical studies suggest that, due to their antiproliferative and anti-inflammatory properties, phosphodiesterase-5 inhibitors (PDE5i) might have an anticancer effect. The aim of this study was to clarify through systematic review and meta-analysis of published peer-reviewed studies whether an association exists between PDE5i use and CRC risk. This study was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective registration was performed on PROSPERO (CRD42022372925). A systematic review was performed for studies reporting CRC and advanced colorectal polyp incidence in PDE5i 'ever-users' and PDE5i 'never-users'. Meta-analysis was performed using RevMan version 5. Four observational cohort studies and two case-control studies, comprising 995 242 patients were included in the final analysis, of whom 347 126 were PDE5i ever-users. Patients who were PDE5i ever-users had a significantly lower incidence of CRC or advanced colorectal polyps than never-users (OR 0.88, CI 0.79-0.98, p = 0.02). To examine the primary preventative role of PDE5i, subgroup analysis of four studies including patients without a previous history of CRC found that use of PDE5i was associated with a lower incidence of CRC (OR 0.85, CI 0.75-0.95, p = 0.005, I2  = 64%). There was no significant temporal relationship found between PDE5i use and CRC risk as both current users and previous users had a significantly lower incidence of CRC than never-users. Our study found a significant anticancer effect of PDE5i, as shown by a reduced risk of CRC in the context of both primary and secondary CRC prevention.

(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&amp;lt;0.0001) and flushing (P&amp;lt;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