Phosphodiesterase-5 Inhibitors Research Articles

Differences in Ocular Adverse Events Associated with phosphodiesterase-5 inhibitors: a real-world pharmacovigilance study

ABSTRACT Background Phosphodiesterase type 5 (PDE5) inhibitors are commonly prescribed for erectile dysfunction and pulmonary hypertension. While PDE5 inhibitors have shown remarkable efficacy in their intended therapeutic areas, there have been concerns regarding their potential ocular adverse events. Our study aims to characterize the ocular safety profiles of PDE5 inhibitors and explore the differences in ocular adverse events among PDE5 inhibitors. Research design and methods We analyzed reports on ocular adverse events associated with sildenafil, vardenafil and tadalafil submitted to the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the first quarter of 2023. Disproportionality analysis was conducted to evaluate reporting risk profiles. Results Among 61,211 reports qualifying for analysis, 5,127 involved sildenafil, 832 vardenafil, and 3,733 tadalafil. All PDE5 inhibitors showed increased reporting odds ratios (ROR) for ocular adverse events, with vardenafil highest (ROR 4.47) followed by sildenafil and tadalafil. Key ocular adverse events included cyanopsia, optic ischemic neuropathy, visual field defects, unilateral blindness and blindness. Sildenafil showed the highest disproportionality for cyanopsia (ROR 1148.11) while vardenafil and tadalafil showed the highest disproportionality for optic ischemic neuropathy. Time-to-onset analysis also revealed significant differences, with sildenafil having a later median time-to-onset compared to vardenafil and tadalafil. Conclusions This comprehensive pharmacovigilance study reveals distinct patterns of ocular adverse events associated with sildenafil, vardenafil, and tadalafil. These findings contribute to a better understanding of the safety profiles of PDE5 inhibitors and may guide healthcare professionals in clinical decision-making.

Prognostic Value and Determinants of High-Sensitivity Cardiac Troponin T in Patients With a Systemic Right Ventricle: Insights From the SERVE Trial.

The determinants and prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) among patients with a systemic right ventricle are largely unknown. Ninety-eight patients from the randomized controlled SERVE (Effect of Phosphodiesterase-5 Inhibition With Tadalafil on Systemic Right Ventricular Size and Function) trial were included. The correlation between baseline hs-cTnT concentrations and biventricular volumes and function quantified by cardiac magnetic resonance or cardiac multirow detector computed tomography was assessed by adjusted linear regression models. The prognostic value of hs-cTnT was assessed by adjusted Cox proportional hazards models, survival analysis, and concordance statistics. The primary outcome was time to the composite of clinically relevant arrhythmia, hospitalization for heart failure, or all-cause death. Median age was 39 (interquartile range, 32-48) years, and 32% were women. Median hs-cTnT concentration was 7 (interquartile range, 4-11) ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index and right ventricular ejection fraction (RVEF) were +0.368 (P=0.046) and -0.381 (P=0.018), respectively. The sex- and age-adjusted hazard ratio for the primary outcome of hs-cTnT at 2 and 4 times the reference level (5 ng/L) were 2.89 (95% CI, 1.14-7.29) and 4.42 (95% CI, 1.21-16.15), respectively. The prognostic performance quantified by the concordance statistics for age- and sex-adjusted models based on hs-cTnT, right ventricular ejection fraction, and peak oxygen uptake predicted were comparable: 0.71% (95% CI, 0.61-0.82), 0.72% (95% CI, 0.59-0.84), and 0.71% (95% CI, 0.59-0.83), respectively. Hs-cTnT concentration was significantly correlated with right ventricular ejection fraction and right ventricular end-systolic volume index in patients with a systemic right ventricle. The prognostic accuracy of hs-cTnT was comparable to that of right ventricular ejection fraction and peak oxygen uptake predicted. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03049540.

Inflammation in cerebral ischemia reperfusion improved by avanafil via nod-like receptor protein-3 inflammasome: an experimental study in rats

ABSTRACT Objective The aim of study was to investigate the effect of avanafil, a second-generation phosphodiesterase-5 (PDE5) inhibitor, on cerebral ischemia reperfusion (CI/R) model. Methods 32 male albino Wistar rats were used. Four groups were constituted, as I: the healthy (sham), II: the CI/R group, III: the CI/R +I 10 mg/kg avanafil group, and IV: the CI/R + 20 mg/kg avanafil group. Avanafil was administered twice via oral gavage, first shortly after ischemia reperfusion and once more after 12 h. The rats were euthanized after 24 h. Histopathological and Real Time PCR analyzes were performed on cerebral tissues. Results IL-1β, NLRP3 and TNF-α mRNA expressions were statistically higher in the CI/R group when compared to healthy (sham) group. Conversely, the IL-1β, NLRP3, and TNF-α mRNA expressions were significantly decreased in both of the avanafil-treated groups when compared to CI/R group. Histopathological results showed that both doses of avanafil also decreased cellular damage in cerebral tissue that occurred after CI/R. Conclusion Avanafil, was found to have ameliorated inflammatory response and cellular injury caused by CI/R. The mRNA expression of IL-1β, NLRP3, and TNF-α decreased in the I/R groups and approached the control group levels with a high dose of avanafil.

Endovascular penile revascularization improves erectile dysfunction in patients with penile arterial insufficiency

In most institutions, patients with erectile dysfunction due to penile arterial insufficiency are offered palliative treatments like vacuum constrictor devices, intraurethral alprostadil, intracavernosal injection of prostaglandins, and/or implantation of penile prosthesis when these patients can be treated by endovascular penile revascularization. 50% of patients with erectile dysfunction are non-responders to phosphodiesterase-5 inhibitors. 70% of non-responders to phosphodiesterase-5 inhibitors have penile arterial insufficiency that can be treated with endovascular penile revascularization. Patients who are non-responders to phosphodiesterase-5 inhibitors should be screened for penile arterial insufficiency using penile duplex scan. If penile artery peak systolic velocity is <35 cm/s, then arterial insufficiency is suspected, and computed tomography (CT) angiogram is obtained to confirm presence of significant stenosis in iliac-pedundle-penile arterial system. Patients with penile arterial insufficiency should be offered endovascular penile revascularization. This minimally invasive procedure has minimal perioperative complications (<1%) and has significant clinical improvement in erectile function in >60% of patients at 12 months. Endovascular penile revascularization is safe and has long term clinical improvement in erectile function. This minimally invasive procedure can result in improved erectile function and preserves penile size and shape in most non-responders to phosphodiesterase-5 inhibitors.

Design, Synthesis, and Evaluation of Dihydropyrimidine Derivatives as Selective PDE1 Inhibitors for the Treatment of Liver Fibrosis.

Liver fibrosis is a common pathological feature of most chronic liver diseases with no effective drugs available. Phosphodiesterase 1 (PDE1), a subfamily of the PDE super enzyme, might work as a potent target for liver fibrosis by regulating the concentration of cAMP and cGMP. However, there are few PDE1 selective inhibitors, and none has been investigated for liver fibrosis treatment yet. Herein, compound AG-205/1186117 with the dihydropyrimidine scaffold was selected as the hit by virtual screening. A hit-to-lead structural modification led to a series of dihydropyrimidine derivatives. Lead 13h exhibited the IC50 of 10 nM against PDE1, high selectivity over other PDEs, as well as good safety properties. Administration of 13h exerted significant anti-liver fibrotic effects in bile duct ligation-induced fibrosis rats, which also prevented TGF-β-induced myofibroblast differentiation in vitro, confirming that PDE1 could work as a potential target for liver fibrosis.

Unmet need in PH-ILD: A clinician survey of real-world management of PH-ILD in Europe

BackgroundWith no approved therapies for pulmonary hypertension (PH) associated with interstitial lung disease (PH-ILD) in Europe, we surveyed clinician perceptions on PH-ILD management and unmet need to understand current real-world practices.Methods: An online clinician survey on PH-ILD management was conducted in France, Germany, Italy, Spain, and the UK.Results: Fifty-five clinicians (78% pulmonologists) each managing a median 20 PH-ILD patients (interquartile range [IQR]=10–50), participated. Upon PH suspicion, clinicians referred a median 50% (IQR=20–73%) of patients for echocardiography alone and 35% (IQR=20–78%) for echocardiography, followed by right heart catheterisation.Upon diagnosis, a median 20% (IQR=9–30%), 40% (IQR=20–50%) and 35% (IQR=20–55%) of patients fell under the pulmonary arterial pressure ranges of 21–24mmHg, 25–34mmHg and >35mmHg respectively. Fifty percent of patients received off-label treatment for their PH and, of those, off-label phosphodiesterase-5 inhibitor (PDE-5i), endothelin receptor antagonist (ERA) and prostacyclin analogues were prescribed first-line by 78%, 9% and 7% of clinicians, respectively. Upon PDE-5i non-response, 35% of clinicians proceed with an ERA, 35% with no further therapy. Fifty-five percent of clinicians used dual therapy. Yearly median inpatient admissions and emergency visits were 2.0 (IQR=1.3–2.9) and 1.5 (IQR=1.0–2.0) respectively (n=31 responses). Most clinicians (69%) highlighted lack of efficacy or evidence for current therapies as a key gap in PH-ILD management.ConclusionsThis study gives insight into real-world European PH-ILD diagnosis and management. With significant use of off-label treatment, there is a large unmet need due to lack of approved therapies. Despite updated guidelines, more evidence is needed to standardise PH-ILD management.

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)

PDE5is-naïve versus non-naïve patients at first investigation for erectile dysfunction-findings from a long-term, real-life cross-sectional study.

Phosphodiesterase 5 inhibitors (PDE5is) represent a first-line pharmacological therapy for erectile dysfunction (ED). Men could obtain PDE5is for recreational purposes without any proper medical prescription. We aimed to analyze clinical characteristics of patients who already used any PDE5i for ED without previous formal medical prescription. Data from 2012 heterosexual, sexually active men seeking first medical help for ED at our outpatient clinic between 2005 and 2022 were analyzed. All patients were assessed with a comprehensive sexual and medical history and completed the International Index of Erectile Function (IIEF) at baseline. Comorbidities were scored with the Charlson comorbidity index (CCI). Thereof, according to exposure to any PDE5i before their first visit, patients were subdivided into: PDE5i-naïve and non-PDE5i-naïve patients. Descriptive statistics tested the sociodemographic and clinical characteristics of both groups. A logistic regression model predicted the likelihood of being PDE5i-naïve at the baseline. Linear regression analysis (LRA) estimated the likelihood of being PDE5i-naïve versus non-PDE5i-naïve over the analyzed timeframe. Lastly, local polynomial regression models graphically explored the likelihood of being PDE5i-naïve at the first clinical assessment over the analyzed timeframe, and the sensitivity analyses tested the probability of being PDE5i-naïve at baseline. Overall, 1,491 (70.9%) patients were PDE5i-naïve and 611 (29.1%) were non-PDE5i-naïve at the first assessment. PDE5is-naïve patients were younger, with a lower prevalence of CCI ≥ 1 and of normal erectile function (EF) than non-PDE5i-naïve men (all p<0.05). Multivariable logistic regression found that patients with lower BMI (OR: 0.99), higher IIEF-EF scores (OR: 1.02), lower rates of severe ED (OR: 0.94), and who had been assessed earlier throughout the study timeframe (OR: 1.27) were less likely to be PDE5i-naïve at baseline. Univariate LRA revealed that younger patients (Coeff: -0.02), with lower CCI (Coeff: -0.29) and higher alcohol intake per week (Coeff: 0.52) were more likely to be PDE5i-naïve over the analyzed timeframe. Moreover, for the same IIEF-EF score, patients with higher CCI had lower probability of being PDE5i-naïve. Self-prescription of PDE5is is an attitude presents in the general population, despite this phenomenon has decreased overtime. Current data outline the importance to keep promoting educational campaigns to promote PDE5is as effective and safe medicinal products, while avoiding their improper use.

Tadalafil for Treatment of Fetal Growth Restriction: A Review of Experimental and Clinical Studies.

Fetal growth restriction (FGR) is a major concern in perinatal care. Various medications have been proposed as potential treatments for this serious condition. Nonetheless, there is still no definitive treatment. We studied tadalafil, a phosphodiesterase-5 inhibitor, as a therapeutic agent for FGR in clinical studies and animal experiments. In this review, we summarize our preclinical and clinical data on the use of tadalafil for FGR. Our studies in mouse models indicated that tadalafil improved FGR and hypertensive disorders of pregnancy. A phase II trial we conducted provided evidence supporting the efficacy of tadalafil in prolonging pregnancy (52.4 vs. 36.8 days; p = 0.03) and indicated a good safety profile for fetuses and neonates. Fetal, neonatal, and infant mortality was significantly lower in mothers receiving tadalafil treatment than that in controls (total number: 1 vs. 7, respectively; p = 0.03), and no severe adverse maternal events associated with tadalafil were observed. Although further studies are needed to establish the usefulness of tadalafil in FGR treatment, our research indicates that the use of tadalafil in FGR treatment may be a paradigm shift in perinatal care.

Tadalafil in Neonates and Infants With Pulmonary Hypertension Secondary to Bronchopulmonary Dysplasia.

The primary outcome of this study was to describe the dosing regimen of tadalafil in neonates and infants diagnosed with pulmonary hypertension (PH) secondary to bronchopulmonary dysplasia (BPD). Secondary outcomes included tolerability, efficacy, adverse events, discontinuation of therapy, and changes in echocardiography. This was a single-center, retrospective review of neonates and infants <1 year of age at initiation of tadalafil for PH secondary to BPD from January 2010 to November 2021. Data collected from the electronic medical record included patient demographics, tadalafil dosing, oxygen support, mechanical ventilation, concomitant PH medications, adverse events, and echocardiography information. Forty-two patients-4 neonates and 38 infants-met the inclusion criteria. The postnatal and post-menstrual age (median, IQR) at diagnosis were 121 (35.5-153.5) days and 42.6 (40.6-47.6) weeks, respectively. The initial and highest tadalafil doses (median, range) were 1 (0.25-2) and 1 (0.5-2) mg/kg/day. Only 1 patient experienced pulmonary overcirculation and required tadalafil to be discontinued. Over half (57.1%) of the patients in this study discontinued tadalafil therapy owing to improvements in pulmonary artery pressures. Tadalafil 1 mg/kg/day was the most commonly used dose regimen in neonates and infants. Tadalafil at this dose of 1 mg/kg/day appears well tolerated in neonates and infants with PH secondary to BPD and correlates with improvements in pulmonary artery pressures. Further studies evaluating tadalafil in comparison to other phosphodiesterase-5 inhibitors in neonates with PH secondary to BPD are warranted.

Which PDE5 inhibitor is the most effective in the treatment of erectile dysfunction in men with spinal cord injury? A systematic review and network meta-analysis.

Phosphodiesterase 5 inhibitors (PDE5i) are the first-line drugs for erectile dysfunction (ED) but differences among available molecules should drive therapy personalization. Choosing one PDE5i over another is a challenge in men with spinal cord injury (SCI), as the evidence of efficacy for each molecule is derived from few studies and comparative "head-to-head" trials are lacking. To assess the efficacy of the different PDE5i for SCI-related ED with a network meta-analysis (NMA) approach. Databases from PubMed, Web of Science, Scopus, and Cochrane Library were checked for randomized controlled trials (RCTs) comparing any PDE5i to each other or placebo in men with traumatic SCI lasting ≥6 months. Data were incorporated in a random-effect NMA, where treatments' efficacy was ranked using the surface under the cumulative ranking curve (SUCRA). The 10 RCTs included provided information about 1,492 men with ED due to traumatic SCI. Intervention arms included sildenafil, tadalafil, and/or vardenafil. Overall, at the pairwise meta-analysis, PDE5i were four times more effective than placebo in improving erectile function (risk ratio: 4.13, 95% CI: 2.76, 6.19). The comparative analysis from NMA revealed that tadalafil was associated with the highest SUCRA value (81%), followed by vardenafil (68%) and sildenafil (49%). Within the grading of comparison network, tadalafil appeared to be the best PDE5i in the treatment of SCI-related ED. Further focused studies are warranted to confirm these findings and define optimal doses and duration of therapy.

Fixed-dose combination therapy in pulmonary arterial hypertension: Pros & cons

Quality of life of patients suffering from chronic diseases is inevitably conditioned by the number of pills taken during the day. To improve patients' tolerability, compliance and quality of life and reduce healthcare costs, pharmaceutical companies are focusing on the commercialization of fixed-dose combination (FDC) therapies.The last ESC/ERS guidelines for the treatment of pulmonary arterial hypertension (PAH) recommend initial dual combination therapy for newly diagnosed patients at low or intermediate mortality risk. In this regard, polypills including an endothelin receptor antagonist (ERA) and a phosphodiesterase 5 inhibitor (PDE5-i) could represent an useful therapeutic strategy, although with some limitations. To date, evidence about the use of FDCs in PAH is limited but future studies evaluating their safety and efficacy are welcome.

Correlates of Plasma NT-proBNP/Cyclic GMP Ratio in Heart Failure With Preserved Ejection Fraction: An Analysis of the RELAX Trial.

Phosphodiesterases degrade cyclic GMP (cGMP), the second messenger that mediates the cardioprotective effects of natriuretic peptides. High natriuretic peptide/cGMP ratio may reflect, in part, phosphodiesterase activity. Correlates of natriuretic peptide/cGMP in patients with heart failure with preserved ejection fraction are not well understood. Among patients with heart failure with preserved ejection fraction in the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure With Preserved Ejection Fraction) trial, we examined (1) cross-sectional correlates of circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide)/cGMP ratio, (2) whether selective phosphodiesterase-5 inhibition by sildenafil changed the ratio, and (3) whether the effect of sildenafil on 24-week outcomes varied by baseline ratio. In 212 subjects, NT-proBNP/cGMP ratio was calculated at randomization and 24 weeks. Correlates of the ratio and its change were examined in multivariable proportional odds models. Whether baseline ratio modified the sildenafil effect on outcomes was examined by interaction terms. Higher NT-proBNP/cGMP ratio was associated with greater left ventricular mass and troponin, the presence of atrial fibrillation, and lower estimated glomerular filtration rate and peak oxygen consumption. Compared with placebo, sildenafil did not alter the ratio from baseline to 24 weeks (P=0.17). The effect of sildenafil on 24-week change in peak oxygen consumption, left ventricular mass, or clinical composite outcome was not modified by baseline NT-proBNP/cGMP ratio (P-interaction >0.30 for all). Among patients with heart failure with preserved ejection fraction, higher NT-proBNP/cGMP ratio associated with an adverse cardiorenal phenotype, which was not improved by selective phosphodiesterase-5 inhibition. Other phosphodiesterases may be greater contributors than phosphodiesterase-5 to the adverse phenotype associated with a high natriuretic peptide/cGMP ratio in HFpEF. clinicaltrials.gov. Identifier: NCT00763867.

Value of phosphodiesterase 5 inhibitors as a combination therapy for treating erectile dysfunction: A literature review

AbstractErectile dysfunction (ED) is increasing in prevalence, with estimates that 50% of men between 40 and 70 years of age suffer from the disease. Due to a wide array of available medical interventions, significant focus has been put on combination therapies that can treat ED refractory to first‐line treatments such as phosphodiesterase 5 inhibitors (PDE5is). However, reviews evaluating monotherapy noninferiority and patient satisfaction of monotherapy versus combination therapy are lacking. A thorough PubMed search was performed to evaluate combination therapy in ED treatment. Articles published between January 2008 and June 2023 were reviewed, including randomized control trials, retrospective analyses, and cohort studies. Combination therapies included PDE5i plus another PDE5i, testosterone supplementation, α‐blockers, vacuum erectile devices, intracavernosal injections, and low‐intensity shockwave therapy. Based on this review, PDE5i monotherapy is not inferior to combination therapy and has increased satisfaction, convenience, and ease of use for patients with ED. Limitations of current literature on combination therapy include small sample size, limited data on patient satisfaction, possible biases, and limited follow‐up time. Further studies will need larger randomized control trials with follow‐up times greater than 1 year.

Bifunctional Sildenafil Diazeniumdiolates Acting as Phosphodiesterase 5 Inhibitors and Nitric Oxide Donors- Towards Wound Healing.

Inefficient wound healing poses a global health challenge with a lack of efficient treatments. Wound healing issues often correlate with low endogenous nitric oxide (NO) levels. While exogenous delivery with NO-releasing compounds represents a promising therapeutic strategy, controlling the release of the highly reactive NO remains challenging. Phosphodiesterase 5 (PDE5) inhibitors, like sildenafil, have also been shown to promote wound healing. This study explores hybrid compounds, combining NO-releasing diazeniumdiolates with a sildenafil-derived PDE5 inhibitor. One compound demonstrated a favorable NO-release profile, triggered by an esterase (prodrug), and displayed in vitro nanomolar inhibition potency against PDE5 and thrombin-induced platelet aggregation. Both factors are known to promote blood flow and oxygenation. Thus, our findings unveil promising prospects for effective wound healing treatments.

Sildenafil as a Candidate Drug for Alzheimer's Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons.

Alzheimer's disease (AD) is a chronic neurodegenerative disease needing effective therapeutics urgently. Sildenafil, one of the approved phosphodiesterase-5 inhibitors, has been implicated as having potential effect in AD. To investigate the potential therapeutic benefit of sildenafil on AD. We performed real-world patient data analysis using the MarketScan® Medicare Supplemental and the Clinformatics® databases. We conducted propensity score-stratified analyses after adjusting confounding factors (i.e., sex, age, race, and comorbidities). We used both familial and sporadic AD patient induced pluripotent stem cells (iPSC) derived neurons to evaluate the sildenafil's mechanism-of-action. We showed that sildenafil usage is associated with reduced likelihood of AD across four new drug compactor cohorts, including bumetanide, furosemide, spironolactone, and nifedipine. For instance, sildenafil usage is associated with a 54% reduced incidence of AD in MarketScan® (hazard ratio [HR] = 0.46, 95% CI 0.32- 0.66) and a 30% reduced prevalence of AD in Clinformatics® (HR = 0.70, 95% CI 0.49- 1.00) compared to spironolactone. We found that sildenafil treatment reduced tau hyperphosphorylation (pTau181 and pTau205) in a dose-dependent manner in both familial and sporadic AD patient iPSC-derived neurons. RNA-sequencing data analysis of sildenafil-treated AD patient iPSC-derived neurons reveals that sildenafil specifically target AD related genes and pathobiological pathways, mechanistically supporting the beneficial effect of sildenafil in AD. These real-world patient data validation and mechanistic observations from patient iPSC-derived neurons further suggested that sildenafil is a potential repurposable drug for AD. Yet, randomized clinical trials are warranted to validate the causal treatment effects of sildenafil in AD.

Medical Advancements in Benign Prostatic Hyperplasia Treatments.

This review aims to identify and summarize the current literature on the most recent therapeutic agents and combination strategies for the medical management of lower urinary tract symptoms resulting from benign prostatic hyperplasia. The latest advancements in BPH therapy have been in combination strategies. Alpha blockers continue to be the mainstay of treatment, but research is exploring the synergistic benefits of combining them with 5-alpha reductase inhibitors (5-ARIs), phosphodiesterase-5 (PDE5) inhibitors, and beta-3 agonists. The alpha-blocker + 5-ARI combination remains ideal for enlarged, significantly reducing clinical progression risk compared to monotherapy. Alpha-blocker + PDE5 inhibitor combinations appear safe and potentially beneficial for men with concomitant erectile dysfunction; sildenafil might hold an edge over tadalafil based on limited data. Beta-3 agonists show synergistic effects with alpha blockers for residual storage symptoms, offering similar efficacy to anticholinergics but with a better side effect profile.

Himplant® subcutaneous penile implant improves penile appearance and erectile dysfunction after radical prostatectomy: a case series.

Erectile dysfunction is a major postoperative complication following radical prostatectomy. Various treatments for post- radical prostatectomy erectile dysfunction including nonsurgical phosphodiesterase-5 inhibitors, intraurethral alprostadil, intracavernosal injections and penile implant prosthesis, often yield suboptimal results. In this prospective single-center case series, we examine the efficacy and outcomes of Himplant®, a subcutaneous silicone penile implant, placement in four patients with post-radical prostatectomy erectile dysfunction who experienced limited benefits with phosphodiesterase-5 inhibitors. Patient data including demographics, prostate cancer diagnoses, erectile dysfunction characteristics, previous treatments, and outcomes were collected. Himplant® placement was performed in a standardized manner through a high scrotal incision in all cases. Follow-up evaluations were conducted to assess the effectiveness of the procedure and any associated complications. Patients were contacted and asked 15 questions regarding satisfaction and erectile function with the responses recorded. This study presents findings of high patient satisfaction, increases in flaccid penile length and girth, no incidence of adverse events, and improved erectile function following Himplant® placement post-radical prostatectomy. Accordingly, we suggest Himplant® placement in patients who are frustrated by their penile appearance and suffering from erectile dysfunction after radical prostatectomy. Further multicenter studies are warranted to validate these findings and assess long-term outcomes and patient-reported satisfaction.

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.