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The Effect of Phosphodiesterase-type 5 Inhibitors on Erectile Function: An Overview of Systematic Reviews.

ABSTRACT: Background: Multiple systematic reviews explore the effect of phosphodiesterase type 5 (PDE5) inhibitors on erectile dysfunction (ED), with each study addressing specific outcomes. However, physicians and policymakers require a holistic approach of this topic. Objective: To summarize the current evidence regarding the efficacy and safety of PDE5 inhibitors for the management of ED through an overview of systematic reviews. Methods: Studies were identified by searching PubMed, Web of Science, Cochrane Library and Scopus databases, as well as sources of grey literature until June 12, 2021 (PROSPERO: CRD42020216754). We considered systematic reviews, meta-analyses or network meta-analyses of randomized trials that provided outcomes about the efficacy and safety of any approved PDE5 inhibitor (avanafil, sildenafil, tadalafil and vardenafil). We constructed forest plots for meta-analytic effects regarding the change in erectile function, adverse events and dropouts after administration of PDE5 inhibitors in the general population and in specific patient groups. Results: We included 23 studies with 154,796 participants and a total of 258 meta-analytic effects. Sildenafil 25 mg [Weighted Mean Difference (WMD): 13.08, 95% Confidence Interval (CI): 10.1-16.06] seemed to be statistically superior to all interventions in improving erectile function compared to placebo, but studies with low-dose sildenafil are lacking. Moreover, comparing among different PDE5 inhibitors, sildenafil 50 mg or sildenafil 100 mg were considered the most effective compounds in the general population. The latter derived, however, predominantly from indirect comparisons among different PDE5 inhibitors. Still, sildenafil 100 mg was associated with more treatment-related adverse events and dropouts. Interestingly, low-dose daily tadalafil may be more effective than high-dose on-demand tadalafil (WMD: 1.24, 95% CI: 0.03-2.44). Furthermore, testosterone and PDE5 inhibitors in patients with ED and hypogonadism seem to further improve symptoms, while the addition of a-blockers in patients with urinary symptoms treated with PDE5 inhibitors does not provide additional benefits (WMD: -0.8, 95% CI: -1.65-0.06). Conclusion: Although the efficacy and safety of PDE5 inhibitors, compared to placebo, is well-documented, the existing evidence comparing different PDE5 inhibitors is low. Therefore, high-quality, head-to-head, trials comparing different PDE5 inhibitors are necessary to determine their ideal dosage and formulation based on their safety and efficacy profile. Systematic Review Registration: PROSPERO, identifier [CRD42020216754].

SUBMITTER: Pyrgidis N

PROVIDER: S-EPMC8452927 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionPhosphodiesterase-type 5 inhibitors (PDE5i) are the recommended first-line treatment for erectile dysfunction. Previous systematic reviews and meta-analyses suggest that they are a safe and effective option in many patient groups. Similarly, PDE5i may be effective as part of combination therapy in non-responders to PDE5i. We will generate an overview of systematic reviews, meta-analyses and network meta-analyses aiming to summarise the available knowledge regarding the efficacy and safety of PDE5i in the general population and in multiple subgroups of patients.Methods and analysisThis overview was designed in accordance with the PRIO-harms and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and its protocol was registered at PROSPERO. We will systematically search PubMed, Web of Science, Cochrane Library and Scopus databases from inception to November 2020 without any language restrictions. We will include systematic reviews or meta-analyses: (1) comparing the efficacy and safety of any dose of PDE5i with each other, with placebo or with other effective treatments for the management of erectile function; (2) exploring the use of any PDE5i alone or in combination with other treatment modalities in the general male population or in specific subgroups and (3) conducted with systematic procedures. Our overview will employ the AMSTAR 2 tool to evaluate the quality of the included studies and the Grading of Recommendations Assessment, Development and Evaluation approach to assess the strength of evidence for all outcomes. We will construct forest plots of risk estimates with the corresponding CI for all outcomes.Ethics and disseminationIn this overview, we will undertake an extensive literature search in an attempt to evaluate the potential benefits and risks of treatment with one PDE5i versus another or versus placebo and provide recommendations for clinicians and policy-makers. No ethical approval is required.Prospero registration numberCRD42020216754.

Project description:IntroductionSexual dysfunction in men is common, and optimal treatment is complex. Although several systematic reviews concerning treatment approaches exist, a comprehensive overview without limitations concerning the population, interventions, or outcomes is lacking.AimTo conduct a "review of reviews" to compare the effectiveness of pharmacologic, non-pharmacologic, and combined interventions.Methods9 electronic databases, relevant journals, and reference lists up to July 2018 were searched. For each intervention, only the most recent and comprehensive meta-analysis or systematic review was included. The methodologic quality of the reviews was appraised using the Assessment of Multiple Systematic Reviews-2 tool.Main outcome measureSexual functioning (via intravaginal ejaculatory latency time and international index of erectile function), sexual satisfaction, and adverse effects.Results30 systematic reviews were included. For premature ejaculation, several treatments, including oral pharmacotherapy (selective serotonin inhibitors, phosphodiesterase type 5 [PDE5] inhibitors, tricyclic antidepressants, and opioid analgesics), topical anesthetics, and combined drug and behavioral therapies demonstrated significant improvements of 1-5 minutes in the intravaginal ejaculatory latency time. Pharmacologic interventions (PDE5 inhibitors, penile injection, and testosterone), shockwave therapy, lifestyle modifications, and combined therapies (PDE5 inhibitors and psychological intervention) were effective in treating erectile dysfunction. Most pharmacologic therapies were associated with adverse effects.ConclusionsThere is suggestive evidence that pharmacologic interventions or combined therapies are more effective than non-pharmacologic interventions for treating sexual dysfunction in men; however, a range of treatment options should be presented to individual patients so they may consider the risks and benefits of treatments differently. Evidence related to behavioral and psychological interventions is insufficient compared with that related to drug trials, highlighting the necessity for larger and better randomized controlled trials. Ciocanel O, Power K, Eriksen A. Interventions to Treat Erectile Dysfunction and Premature Ejaculation: An Overview of Systematic Reviews. Sex Med 2019;7:251-269.

Project description:BackgroundLow-intensity extracorporeal shockwave therapy (LI-ESWT) may be a successful complementary treatment approach for erectile dysfunction (ED). In this study, we aimed to review and summarize the research evidence from systematic reviews (SRs)/meta-analyses (MAs) regarding the clinical effectiveness of LI-ESWT for ED.MethodsStudies on LI-ESWT for ED were searched using eight electronic databases from establishment of each database to 31 June 2021 with the language restrictions of Chinese and English. All articles were screened, and qualifying data were recorded based on the inclusion criteria. Methods including: the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2); the Risk of Bias in Systematic Reviews (ROBIS); the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); and Grading of Recommendations, Assessment Development, and the Evaluation (GRADE) were used by two independent raters to assess methodological quality, risk of bias, reporting quality, and SR evidence of quality, respectively.ResultsEight SRs/MAs met all inclusion criteria. Seven reviews were rated as critically low on overall confidence and one review was low on confidence based on the AMSTAR-2 appraisal tool. While most PRISMA criteria were met, the major reporting flaws were in relation the financial statements not being included, along with no protocol registrations. Three SRs/MAs were classed as low risk regarding bias as measured by the ROBIS tool. Based on the GRADE method, only one SRs/MAs of high-quality evidence and seven SRs/MAs of moderate-quality evidence were found. The present research results supported LI-ESWT as a complementary therapy for ED patients, but the evidence should be considered carefully due to the methodological flaws identified.DiscussionOur results showed that LI-ESWT as an adjunctive therapy has benefits for ED patients. There were no obvious side effects, and the number of shockwave treatments and energy flux density (EFD) would affect the IIEF-EF, EHS and PSV scores. However, due to the limited sample size and the quality of reporting evidence, our conclusions may not be fully representative.

Project description:Prostate cancer is relatively common cancer occurring in males. Radical prostatectomy (RP) is the most effective treatment for a localized tumor but erectile dysfunction (ED) is common complication, even when bilateral nerve-sparing RP (BNSRP) is performed. Clinical trials have shown varied effectiveness of phosphodiesterase type-5 inhibitors (PDE5-Is) for treatment of post-BNSRP ED, but there remains controversy over the application of this treatment and no formal systematic review and meta-analysis for the use of PDE5-Is for this condition has been conducted. This review was to systematically assess the efficacy and safety of oral PDE5-Is for post-BNSRP ED. A database search was conducted to identify randomized controlled trials (RCTs). The comparative efficacy of treatments was analyzed by fixed or random effect modeling. Erectile function was measured using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP) question-2, 3 and the Global Assessment Question (GAQ). The rate and incidence of adverse events (AEs) were determined. The quality of included studies was appraised using the Cochrane Collaboration bias appraisal tool. Eight RCTs were included in the analyses. PDE5-Is were effective for treating post-BNSRP ED compared to placebo when erectile function was determined using the IIEF score [mean difference (MD) 5.63, 95% confidence interval (CI) (4.26-6.99)], SEP-2 [relative risk (RR) 1.63, 95% CI (1.18-2.25) ], SEP-3 [RR 2.00, 95% CI (1.27-3.15) ] and GAQ [RR 3.35, 95% CI (2.68-4.67) ]. The subgroup analysis could find a trend that longer treatment duration, higher dosage, on-demand dosing, sildenafil and mild ED are associated with more responsiveness to PDE5-Is. PDE5-Is were overall well tolerated with headache being the most commonly reported AE. Our data provides compelling evidence for the use of PDE5-Is as a primary treatment for post-BNSRP ED. However, further studies are required to optomize usage parameters (such as dosage and duration of treatment).

Project description:Introduction: Amphetamine-type stimulants (ATS) use is a global concern due to increased usage and the harm to physical, mental, and social well-being. The objective of this overview of systematic reviews is to summarise trial results of psychosocial interventions and describe their efficacy and safety. Methods: We searched seven bibliographic databases to November 2020 for systematic reviews examining ATS misuse treatment by psychosocial interventions. Given the apparent incompleteness of the included reviews, we undertook a supplemental meta-analysis of all eligible primary studies. Results: We included 11 systematic reviews of moderate to high quality and 39 primary studies which assessed the outcomes of psychosocial interventions on people who use ATS. The key findings include: (1) There were conflicting results about the effectiveness of psychosocial interventions among reviews, which may confuse decision-makers in selecting treatment. (2) In the supplemental meta-analysis, relative to usual care (only counselling or self-help materials), membership of a psychological intervention group was associated with an important reduction in drug usage [risk ratio (RR) 0.80, 95% CI: 0.75 to 0.85]. Patients in psychological interventions used injectables substantially less [odds ratio (OR) 0.35, 95% CI: 0.24 to 0.49]. The risk of unsafe sex in the psychosocial intervention group was lower than in the control group (RR 0.49, 95% CI: 0.34 to 0.71). The combination of therapies reduced 1.51 day using drugs in the preceding 30 days (95% CI: -2.36 to -0.67) compared to cognitive behavioural therapy intervention alone. (3) Compared to usual care, cognitive behavioural therapy was less likely to be retained at follow-up (RR 0.89, 95% CI: 0.82 to 0.97; high-quality evidence). However, the additional of contingency management strategy can make an important improvement upon retention (RR 1.42, 95%CI: 1.25 to 1.62). Authors' Conclusions: Integrated models are more effective than a single-treatment strategy. Comprehensive and sustained psychosocial interventions can help to reduce use of ATS and other drugs, risk behaviours and mental disorders, and significantly improve treatment adherence.

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The Effect of Phosphodiesterase-type 5 Inhibitors on Erectile Function: An Overview of Systematic Reviews.

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