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Phosphodiesterase 5 inhibitors (PDE5-is) are used worldwide as first line therapy for erectile dysfunction (ED). Current literature reported data on the warning association between PDE5-is use and the development of cutaneous melanoma. However, these data are contrasting, thus we aim to summarise evidence regarding this association. A systematic review of all published articles related to the effects of PDE5-is in the development of cutaneous melanoma was performed. PubMed, EMBASE, and Cochrane library were queried for all the published studies indexed up to the 26th of May 2023. A combination of keywords related to PDE5-is and melanoma were used. Only original studies based on human subjects in the English language were included in the analysis. Of 505 articles identified, only eight original articles were considered for further analysis. Overall, five of the selected articles including 657,984 subjects agrees on an increased risk of developing melanoma in PDE5-is users. On the other hand, three original articles based on data regarding 360,915 subjects, disagree with the previous statement declaring any association between PDE5-i use and melanoma. Current literature still reports contrasting data regarding the association between PDE5-is assumption and increased risk of melanoma, but a possible association is described, bringing attention to higher risk melanoma category of patients. More clinical studies are needed to clarify the impact of PDE5-is in the development and progression of melanoma. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the prevalence of DM among patients with ED and the impact of glycometabolic compensation and antihyperglycemic treatment on ED severity. Methods: In total, 1332 patients with ED were enrolled. The diagnosis was performed through the International-Index-of-Erectile-Function questionnaire. ED severity was considered according to presence/absence of spontaneous erections, maintenance/achievement deficiency and response to PDE5-i. DM patients were clustered according to antihyperglycemic treatment: "metformin"/"insulin"/"old antihyperglycemic drugs"/"new antihyperglycemic drugs". Results: The prevalence of DM patients was 15.8% (Group A, patients with ED and DM). Among these, the prevalence of spontaneous erections (21.0%) was lower than in the remaining patients (Group B, patients with ED without DM) (32.0%, p < 0.001). The prevalence of poor response to PDE5-i was lower in Group B (10.0%) than in Group A (35.0%, p < 0.001). Patients with good response to PDE5-i therapy showed lower HbA1c values than patients with poor/no response (6.6 ± 1.1% vs. 7.7 ± 1.9%, p = 0.02). The prevalence of absent response to PDE5-i was higher in patients treated with old antidiabetic drugs than in the population treated with new drugs (p = 0.03). Conclusion: The severity of ED and lower response to PDE5-i were higher in DM patients. A better glycometabolic profile, as well as new antihyperglycemic drugs, seem to have a positive effect on ED. [ABSTRACT FROM AUTHOR]

Introduction The United Kingdom is unusual in that a significant proportion of patients with erectile dysfunction ( ED) have their treatment fully reimbursed by the National Health Service ( NHS). This may have consequences for the choice of treatment and for compliance with treatment. Aims The aim of this study was to evaluate the use and cost implications of phosphodiesterase type 5 inhibitor in an NHS setting. Methods Basic demographics and data on ED management for patients treated from January 2000 to April 2011 were obtained from a prospectively accrued database. We reviewed drug usage and costs as well as switching between drugs. Patients were given the choice of all available therapies and were followed up annually. Main Outcome Measures Switching, compliance, and costs of treating ED under the 'severe distress' criteria in the NHS were reviewed for this study. Results Two thousand one hundred fifty-nine patients qualified for reimbursed therapy. Two hundred twenty-six patients were excluded from further analysis owing to missing data. Patients were followed up on an annual basis. The mean patient age was 60.2 years (min 23, max 90), and the mean follow-up was 50.8 months (min 1, max 127). Six hundred ninety-six were started on sildenafil, 990 on tadalafil, 163 on vardenafil, and 84 on intracavernosal alprostadil. Eighteen percent of patients initially started on the scheme and stopped medication unilaterally. Of the patients, 12.3% changed their medication during follow-up. The cost of drugs increased year by year from £257,100 in 2007 to £352,519 in 2011. Conclusions Our real-life observational study shows that in our institution, dropout of therapy is unusual. We hypothesize that this reflects, in part, the reimbursement issue. We also found that switching between drugs was unusual, although there are several possible explanations for that. Although this is a successful system for the patients, the hospital, which bears the costs of medication, is finding this an increasing economic drain. Mohee A, Bretsztajn L, Storey A, and Eardley I. Management of ED under the 'severe distress' criteria in the NHS: A real-life study. J Sex Med 2014;11:1056-1062. [ABSTRACT FROM AUTHOR]

Epidemiologic data in adult men exhibit a strong relationship between erectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH), indicating that men affected by ED should also be investigated for LUTS/BPH and those presenting with storage or voiding LUTS should be investigated for co-morbid ED. Common pathophysiolgical mechanisms underlying both LUTS/BPH and ED, including alteration of NO/cGMP or RhoA/Rho-kinase signaling and/or vascular or neurogenic dysfunction, are potential targets for proposed phosphodiesterase type 5 inhibitors (PDE5-Is). Several randomized controlled trials and only a few reviews including all commercially available PDE5-Is demonstrated the safety and efficacy of these drugs in the improvement of erectile function and urinary symptoms, in patients affected either by ED, LUTS, or both conditions. [ABSTRACT FROM AUTHOR]

Abstract: Context: Several randomized controlled trials (RCTs) on phosphodiesterase type 5 inhibitors (PDE5-Is) have showed significant improvements in both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in men affected by one or both conditions, without a significant increase in adverse events. However, the results are inconsistent. Objective: Perform a systematic review and meta-analysis of available prospective and cross-sectional studies on the use of PDE5-Is alone or in combination with α1-adrenergic blockers in patients with LUTS/benign prostatic hyperplasia (BPH). Evidence acquisition: A systematic search was performed using the Medline, Embase, and Cochrane Library databases through September 2011 including the combination of the following terms: LUTS, BPH, PDE5-Is, sildenafil, tadalafil, vardenafil, udenafil, α-blockers, and α1-adrenergic blocker. The meta-analysis was conducted according to the guidelines for observational studies in epidemiology. Evidence synthesis: Of 107 retrieved articles, 12 were included in the present meta-analysis: 7 on PDE5-Is versus placebo, with 3214 men, and 5 on the combination of PDE5-Is with α1-adrenergic blockers versus α1-adrenergic blockers alone, with 216 men. Median follow-up of all RCTs was 12 wk. Combining the results of those trials, the use of PDE5-Is alone was associated with a significant improvement of the International Index of Erectile Function (IIEF) score (+5.5; p <0.0001) and International Prostate Symptom Score (IPSS) (−2.8; p <0.0001) but not the maximum flow rate (Qmax) (−0.00; p = not significant) at the end of the study as compared with placebo. The association of PDE5-Is and α1-adrenergic blockers improved the IIEF score (+3.6; p <0.0001), IPSS score (−1.8; p = 0.05), and Qmax (+1.5; p <0.0001) at the end of the study as compared with α-blockers alone. Conclusions: The meta-analysis of the available cross-sectional data suggests that PDE5-Is can significantly improve LUTS and erectile function in men with BPH. PDE5-Is seem to be a promising treatment option for patients with LUTS secondary to BPH with or without ED. [Copyright &y& Elsevier]

Abstract: Context: This review focuses on the relationship among sexual dysfunction (SD), lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), and related therapies. Objective: We reviewed the current literature to provide an overview of current data regarding epidemiology and pathophysiology of SD and LUTS. Moreover, we analysed the impact of currently available therapies of LUTS/BPH on both erectile dysfunction (ED) and ejaculatory dysfunction and the effect of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with ED and LUTS. Evidence acquisition: We conducted a Medline search to identify original articles, reviews, editorials, and international scientific congress abstracts by combining the following terms: benign prostatic hyperplasia, lower urinary tract symptoms, sexual dysfunction, erectile dysfunction, and ejaculatory dysfunction. Evidence synthesis: We conducted a comprehensive analysis of more relevant general population–based and BPH/LUTS or SD clinic-based trials and evaluated the common pathophysiologic mechanisms related to both conditions. In a further step, the overall impact of current BPH/LUTS therapies on sexual life, including phytotherapies, novel drugs, and surgical procedures, was scrutinized. Finally, the usefulness of PDE5-Is in LUTS/BPH was critically analysed, including preclinical and clinical research data as well as possible mechanisms of action that may contribute to the efficacy of PDE5-Is with LUTS/BPH. Conclusions: Community-based and clinical data demonstrate a strong and consistent association between LUTS and ED, suggesting that elderly men with LUTS should be evaluated for SD and vice versa. Pathophysiologic hypotheses regarding common basics of LUTS and SD as discussed in the literature are (1) alteration of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway, (2) enhancement of RhoA–Rho-kinase (ROCK) contractile signalling, (3) autonomic adrenergic hyperactivity, and (4) pelvic atherosclerosis. The most important sexual adverse effects of medical therapies are ejaculation disorders after the use of some α-blockers and sexual desire impairment, ED, and ejaculatory disorders after the use of α-reductase inhibitors. Minimally invasive, conventional, and innovative surgical treatments for BPH may induce both retrograde ejaculation and ED. PDE5-Is have demonstrated significant improvements in both LUTS and ED in men with BPH; combination therapy with PDE5-Is and α1-adrenergic blockers seems superior to PDE5-I monotherapy. [Copyright &y& Elsevier]

Introduction. Phosphodiesterase type 5 inhibitors (PDE5-I) have acquired an established role in the treatment of post-prostatectomy erectile dysfunction (ED). Several trials in men with ED and lower urinary tract symptoms associated with benign prostatic hyperplasia suggest that PDE5-I could improve both erectile function and urinary symptoms. Aim. To assess the role of vardenafil in continence recovery after bilateral nerve sparing radical prostatectomy (BNS-RP). Methods. Thirty-nine patients with prostate cancer were recruited. After BNS-RP, patients were double-blinded assigned to three arms: a) vardenafil on demand; b) vardenafil nightly; and c) placebo. Main Outcomes Measures. Urinary function (UF) and urinary bother (UB) of University of California–Los Angeles Prostate Cancer Index questionnaire were assessed preoperatively and at 1, 3, 6, 9, 10, and 12 months. Twelve-month outcomes were compared to 1 month with a t-test. The differences in UF and UB (at 3, 6, 9, 10, and 12 months) between the three treatment arms were calculated by an analysis of variance. With ALLFIT we estimated half-maximal recovery times (ER50) and maximal recovery ( Rmax) in three groups. Results. The improvement of UF and UB between 1 and 12 months was significant in all arms except for placebo (UF: P = 0.125; UB: P = 0.089). Nightly resulted in greater UF at 3, 6, and 9 months and greater UB at 6 months compared with placebo ( P = 0.042, P = 0.044 and P = 0.039); after nightly administration, patients presented higher UB than after on-demand use, 3 and 6 months postoperatively ( P = 0.036 and P = 0.017). ALLFIT demonstrated a similar ER50 in all groups (2.6 months for both UF and UB) and indicated that nightly administration induced significant improvements in Rmax compared with placebo (both <0.0001). Conclusions. Vardenafil can improve continence recovery after BNS-RP compared with placebo. The daily use of vardenafil seems to provide better continence rate, although it does not seem to influence the timing needed to achieve full continence. Gacci M, Ierardi A, Delle Rose A, Tazzioli S, Scapaticci E, Filippi S, Maggi M, Nicita G, Carini M, and Montorsi F. Vardenafil can improve continence recovery after bilateral nerve sparing prostatectomy: Results of a randomized, double blind, placebo-controlled pilot study. J Sex Med 2010;7:234–243. [ABSTRACT FROM AUTHOR]

Aims: A) to evaluate the prevalence of patients affected by Diabetes Mellitus (DM) in a population of men with Erectile Dysfunction (ED); B) to define the epidemiological, biochemical and therapeutic aspects., Materials and Methods: N.934 subjects referred at our Andrology Unit for ED were studied. The diagnosis of ED was evaluated using the IIEF-5 questionnaire (Total score ≤21)., Results: The prevalence of subjects affected by DM in a population of men with ED was 19.5% (182/934). The age ranges were: ≥55 years (108/182; 59.3%); ≥40<55 years (70/182; 38.5%); <40 years (4/182; 2.2%). HbA1c mean value was 7.9% ± 0.8%. No significant differences were found in DM onset timing or in anti-diabetic treatment. In n.125/182 cases (68.7%) the ED onset followed the diagnosis of DM; in n.34/182 cases (18.7%) it appeared at the same time; and in n.23/182 cases (12.6%) appeared before DM diagnosis., Ed Treatment: in n.18/182 subjects (9.9%) there was a concomitant hypotestosteronemia; these patients were treated only with testosterone replacement; this treatment was efficacious (IIEF-5 total score ≥22) in 8/18 subjects (44.4%). In n.146/182 subjects (80.2%) a treatment with PDE5-i was given. Of these 146 subjects, the therapy was given "on demand" to 108 subjects (efficacy in 50.9%; 55/108) and "once a day" to the remaining 38 subjects (efficacy 63.1%, 24/38) (p=0.428, n.s.). N.15/182 subjects (8.2%) were treated with intracavernous injections of Alprostadil (efficacy in 8/15, 53.3%). In n.3/182 subjects (1.6%) a penile prosthesis was implanted., Conclusions: DM is one of the most frequent organic causes of ED; there were many strategies to treat this symptom without interfering with the antidiabetic treatment. Finally, ED can be predictive of DM.

Introduction: Several drugs, currently used to treat lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), can be associated with bothersome sexual side effects, including ejaculatory dysfunction (EjD)., Aim: To provide a systematic review and meta-analysis of the available randomized clinical trials (RCTs) reporting the impact of medical treatments for LUTS due to BPH on ejaculatory function., Main Outcome Measure: EjD related to medical treatments for LUTS., Methods: A systematic literature search was performed using PubMed, Scopus and Cochrane databases. EjD was identified using both free text ("ejaculat*," "retrograde ejaculation," "anejaculation," "ejaculatory dysfunction") and Mesh ("Ejaculation") searches., Results: Of 101 retrieved articles, 23 were included in the present meta-analysis. EjD was significantly more common with alpha-blockers (ABs) than with placebo (OR:5.88; P < 0.0001), in particular, considering Tamsulosin (OR:8.58; P = 0.006) or Silodosin (OR:32.5; P < 0.0001), with Tamsulosin associated with significantly lower risk of EjD than Silodosin (OR:0.09; P < 0.00001). Conversely, Doxazosin and Terazosin were associated with a risk similar to placebo. Meta-regression showed that EjD was associated with IPSS and with Qmax both before and after treatment with ABs, while multivariate analysis demonstrated that EjD was independently associated with the improvement of IPSS (adj.r:0.2012; P < 0.0001) and Qmax (adj.r:0.522; P < 0.0001). EjD was significantly more common with 5ARIs as compared with placebo (OR:2.73; P < 0.0001). Both Finasteride (OR 2.70; P < 0.0001) and Dutasteride (OR 2.81; P = 0.0002) were associated with significantly higher risk of EjD than placebo. EjD was significantly more common with combination therapy as compared with ABs alone (OR:3.75; P < 0.0001),or with 5ARIs alone (OR:2.76; P = 0.02)., Conclusions: ABs and 5ARI were both associated with significantly higher risk of EjD than placebo. More the AB is effective over time, greater is the incidence of EjD. Finasteride has the same risk of Dutasteride to cause EjD. Combination therapy with ABs and 5ARIs resulted in a 3-fold increased risk of EjD as compared with ABs or 5ARIs alone. These data can be relevant both for drug selection and patients counseling., (© 2014 International Society for Sexual Medicine.)

Purpose: An epidemiological association between lower urinary tract symptoms and erectile dysfunction is well established. However, interactions among multiple risk factors and the role of each in pathological mechanisms are not fully elucidated, Materials and Methods: We enrolled 898 men undergoing prostate cancer screening for evaluation with the International Prostate Symptom Score (I-PSS) and simplified International Index of Erectile Function-5 (IIEF-5) questionnaires. Age, race, hypertension, diabetes, dyslipidemia, metabolic syndrome, cardiovascular disease, serum hormones and anthropometric parameters were also evaluated. Risk factors for erectile dysfunction were identified by logistic regression. The 333 men with at least mild to moderate erectile dysfunction (IIEF 16 or less) were included in a latent class model to identify relationships across erectile dysfunction risk factors., Results: Age, hypertension, diabetes, lower urinary tract symptoms and cardiovascular event were independent predictors of erectile dysfunction (p<0.05). We identified 3 latent classes of patients with erectile dysfunction (R2 entropy=0.82). Latent class 1 had younger men at low cardiovascular risk and a moderate/high prevalence of lower urinary tract symptoms. Latent class 2 had the oldest patients at moderate cardiovascular risk with an increased prevalence of lower urinary tract symptoms. Latent class 3 had men of intermediate age with the highest prevalence of cardiovascular risk factors and lower urinary tract symptoms. Erectile dysfunction severity and lower urinary tract symptoms increased from latent class 1 to 3., Conclusions: Risk factor interactions determined different severities of lower urinary tract symptoms and erectile dysfunction. The effect of lower urinary tract symptoms and cardiovascular risk outweighed that of age. While in the youngest patients lower urinary tract symptoms acted as a single risk factor for erectile dysfunction, the contribution of vascular disease resulted in significantly more severe dysfunction. Applying a risk factor interaction model to prospective trials could reveal distinct classes of drug responses and help define optimal treatment strategies for specific groups., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)