-
Medicine Dec 2018We performed the network meta-analysis (NMA) and systematic review involved all evidence from relevant trials to compare the efficiency and safety of various types of... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy and safety of phosphodiesterase-5 inhibitors with selective serotonin reuptake inhibitors in men with premature ejaculation: A systematic review and Bayesian network meta-analysis.
BACKGROUND
We performed the network meta-analysis (NMA) and systematic review involved all evidence from relevant trials to compare the efficiency and safety of various types of selective serotonin reuptake inhibitors (SSRI) and phosphodiesterase-5 inhibitors (PDE5i) in patients with premature ejaculation (PE).
METHODS
We conducted comprehensive searches of peer-reviewed and grey literature. PubMed, the Cochrane Library Central Register of Controlled Trials, Embase were searched for randomized controlled trials published up to June 1, 2017. The primary outcome was intravaginal ejaculation latency time (IVELT) and adverse effects (AEs). We performed pairwise meta-analyses by random effects model and network meta-analysis by Bayesian model. We used the GRADE framework to assess the quality of evidence contributing to each network estimate.
RESULTS
Of 3046 titles and abstracts initially identified, 17 trials reporting 5739 participants were included. Considering IVELT in the NMA, paroxetine plus sildenafil and sildenafil alone are both superior to placebo (MD: 1.75, 95% CrI: 0.05 to 3.78; MD 1.43, 95% CrI 0.003 to 2.81). Sildenafil is superior to sertraline (MD: 1.63, 95% CrI: 0.10 to 2.79). Considering AEs, placebo demonstrated obviously lower risk comparing to paroxetine, sildenafil and paroxetine plus sildenafil (OR 0.20, 95% CI: 0.05 to 0.52; OR 0.23, 95% CI: 0.04 to 0.80; OR 0.45, 95% CI: 0.01 to 0.92). Compared with tadalafil plus paroxetine, dapoxetine showed significantly less AEs (OR 0.23, 95% CI 0.02 to 0.96).
CONCLUSIONS
Our study concluded that although paroxetine plus sildenafil and sildenafil alone both demonstrated significant IVELT benefit compared with placebo, significant increase of AEs risk was also observed. Furthermore, sildenafil alone was superior to sertraline in efficacy with comparable tolerability.
Topics: Bayes Theorem; Humans; Male; Phosphodiesterase 5 Inhibitors; Premature Ejaculation; Selective Serotonin Reuptake Inhibitors
PubMed: 30544399
DOI: 10.1097/MD.0000000000013342 -
International Urology and Nephrology Nov 2018The purpose of the study was to conduct a systematic evaluation of the different general prescribed drugs for premature ejaculation (PE). (Meta-Analysis)
Meta-Analysis
PURPOSE
The purpose of the study was to conduct a systematic evaluation of the different general prescribed drugs for premature ejaculation (PE).
METHODS
A systematic literature search of MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science for Systematic Reviews was performed on 1 March 2018. Intravaginal ejaculation latency time (IELT) was the main outcome. Analysis was performed under multivariate random-effects network model and efficacies of drugs were ranked with surface under the cumulative ranking (SUCRA) probabilities.
RESULTS
A total of 48 studies were reviewed and 40 of them were further enrolled into network meta-analysis. The majority of RCTs were of unclear methodological quality. Pooled evidence suggested that topical anaesthetic creams (TAs), tramadol, selective serotonin reuptake inhibitors (SSRIs), and phosphodiesterase type 5 inhibitors (PDE5is) are more effective at prolonging IELT comparing with placebo. TAs (90%) on demand (OD) and PDE5is plus SSRI (89.8%) had the highest SUCRA, which meant the most probable to be the most effective intervention.
CONCLUSIONS
We recommend the initial use of dapoxetine 30 mg OD for PE because it has been tested in largest and better designed clinical trials rather than it is more effective than the other drugs studied. TAs and tramadol 50 mg OD can be used as a viable alternative to oral treatment with SSRIs. PDE5is combined with SSRIs are more effective than SSRIs monotherapy but are also associated with more side effects. PDE5is OD can be recommended to PE patients with ED.
Topics: Analgesics, Opioid; Anesthetics, Local; Humans; Male; Phosphodiesterase 5 Inhibitors; Premature Ejaculation; Selective Serotonin Reuptake Inhibitors; Tramadol
PubMed: 30225547
DOI: 10.1007/s11255-018-1984-9 -
Sexual Medicine Reviews Jan 2019Besides erectile dysfunction, premature ejaculation (PE) is the most frequent male sexual disorder and shows a high level of bother and distress. The negative...
INTRODUCTION
Besides erectile dysfunction, premature ejaculation (PE) is the most frequent male sexual disorder and shows a high level of bother and distress. The negative consequences of long-term and unsuccessfully treated PE on both patient and partner are well established in the literature and include personal distress, impairment of the partner's sexual function, and interpersonal difficulties.
AIM
To outline the consequences of untreated PE and the advantages and disadvantages of currently available treatment options with a special focus on a new topical eutectic lidocaine/prilocaine metered dose spray (Fortacin; Lidocaine/Prilocaine, Recordati, Milan, Italy) which represents the second officially approved drug in this indication.
METHODS
Narrative overview of the literature synthesizing the findings of literature retrieved from searches of computerized databases such as Web of Science, Medline, PubMed, and Google Scholar, hand searches, and authoritative texts. Combinations of keywords including premature ejaculation, ejaculatory control, intravaginal ejaculation latency time, IELT, PE, PDE5 inhibitors (PDE5i), SSRIs, topical anesthetics, lidocaine, prilocaine, and treatment were used. In the end, 59 studies published between 2000 and 2018 were considered relevant for this review.
MAIN OUTCOME MEASURES
Published studies on PE-related negative psychosocial outcomes, as well as advantages and disadvantages of currently available off-label and officially approved treatment options.
RESULTS
Although a variety of treatment options for PE have shown marked improvements in stopwatch-measured intravaginal ejaculation latency time (IELT) and patient-reported outcomes as assessed by the Premature Ejaculation Profile (PEP), none of the investigated drugs has reached market approval. The only so far officially approved medication-dapoxetine-is characterized by high discontinuation rates of up to 90%, mostly because of high side effects, cost issues, efficacy below expectations, and the need for scheduling sexual intercourse.
CONCLUSION
With the official approval in Europe the new dose-metered lidocaine-prilocaine spray (Fortacin) may become a real first-line therapy option for PE and may offer a satisfactory and affordable solution, especially because of its unique galenic preparation, making its handling easy and customer friendly. In addition, it has the potential to significantly increase the currently low patients' acceptance of available monotherapies and become an established second-line therapy for the severe PE patients with IELTs <1 to 2 minutes or with ante-portal ejaculation in combination with oral therapy. Porst H, Burri A. Novel treatment for premature ejaculation in the light of currently used therapies: A review. Sex Med Rev 2019; 7:129-140.
Topics: Benzylamines; Coitus; Ejaculation; Humans; Male; Naphthalenes; Patient Satisfaction; Penile Erection; Phosphodiesterase 5 Inhibitors; Premature Ejaculation; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 30057136
DOI: 10.1016/j.sxmr.2018.05.001 -
Expert Opinion on Investigational Drugs Jul 2018The prevalence of sexual dysfunctions has increased over the last decades; despite a number of available treatments for erectile dysfunction (ED), premature ejaculation... (Review)
Review
INTRODUCTION
The prevalence of sexual dysfunctions has increased over the last decades; despite a number of available treatments for erectile dysfunction (ED), premature ejaculation (PE), and Peyronie's disease (PD), still several unmet therapeutic needs deserve to be fulfilled. The aim of this review is to detail on phase I and II clinical trials investigating novel medical treatments for ED, PE, and PD.
AREAS COVERED
We conducted a systematic review of the literature including both published and ongoing phase I and II registered trials focused on medical treatment of ED, PE, and PD during the last 5 years. A total of 35 trials have been identified. Most studies (63%) investigated ED treatments and 26% were still ongoing. Stem cells (SCs) therapy was assessed in 28% of trials.
EXPERT OPINION
SCs therapy represent a promising treatment for ED although only few patients have been treated to date. Likewise, the oral selective oxytocin receptor antagonists for treating PE showed excellent safety profile and deserve further investigations in phase III trials. Preliminary results of novel topical treatments for PD with fibrinolytic and antiinflammatory drugs are encouraging, but urgently need to be confirmed in large placebo-controlled trials.
Topics: Animals; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Design; Erectile Dysfunction; Humans; Male; Penile Induration; Premature Ejaculation; Prevalence; Stem Cell Transplantation
PubMed: 29969332
DOI: 10.1080/13543784.2018.1495707 -
The Journal of Sexual Medicine Apr 2018Sexual dysfunction is a common problem among men and women and is associated with negative individual functioning, relationship difficulties, and lower quality of life. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sexual dysfunction is a common problem among men and women and is associated with negative individual functioning, relationship difficulties, and lower quality of life.
AIM
To determine the magnitude of associations between 6 health-related lifestyle factors (cigarette smoking, alcohol intake, physical activity, diet, caffeine, and cannabis use) and 3 common sexual dysfunctions (erectile dysfunction, premature ejaculation, and female sexual dysfunction).
METHODS
A comprehensive literature search of 10 electronic databases identified 89 studies that met the inclusion criteria (452 effect sizes; N = 348,865). Pooled mean effects (for univariate, age-adjusted, and multivariable-adjusted estimates) were computed using inverse-variance weighted random-effects meta-analysis and moderation by study and population characteristics were tested using random-effects meta-regression.
RESULTS
Mean effect sizes from 92 separate meta-analyses provided evidence that health-related lifestyle factors are important for sexual dysfunction. Cigarette smoking (past and current), alcohol intake, and physical activity had dose-dependent associations with erectile dysfunction. Risk of erectile dysfunction increased with greater cigarette smoking and decreased with greater physical activity. Alcohol had a curvilinear association such that moderate intake was associated with a lower risk of erectile dysfunction. Participation in physical activity was associated with a lower risk of female sexual dysfunction. There was some evidence that a healthy diet was related to a lower risk of erectile dysfunction and female sexual dysfunction, and caffeine intake was unrelated to erectile dysfunction. Publication bias appeared minimal and findings were similar for clinical and non-clinical samples.
CLINICAL TRANSLATION
Modification of lifestyle factors would appear to be a useful low-risk approach to decreasing the risk of erectile dysfunction and female sexual dysfunction.
STRENGTHS AND LIMITATIONS
Strengths include the testing of age-adjusted and multivariable-adjusted models and tests of potential moderators using meta-regression. Limitations include low statistical power in models testing diet, caffeine, and cannabis use as risk factors.
CONCLUSION
Results provide compelling evidence that cigarette smoking, alcohol, and physical activity are important for sexual dysfunction. Insufficient research was available to draw conclusions regarding risk factors for premature ejaculation or for cannabis use as a risk factor. These findings should be of interest to clinicians treating men and women with complaints relating to symptoms of sexual dysfunction. Allen MS, Walter EE. Health-Related Lifestyle Factors and Sexual Dysfunction: A Meta-Analysis of Population-Based Research. J Sex Med 2018;15:458-475.
Topics: Female; Health Behavior; Humans; Life Style; Male; Risk Factors; Sexual Dysfunction, Physiological
PubMed: 29523476
DOI: 10.1016/j.jsxm.2018.02.008 -
Actas Urologicas Espanolas 2018The revolution of digital technologies constitutes a new setting for the patient-physician relationship and provides patients with a scenario of privacy and universal...
CONTEXT
The revolution of digital technologies constitutes a new setting for the patient-physician relationship and provides patients with a scenario of privacy and universal access to a vast amount of information. However, there is little information on how digital resources are used and what their advantages and disadvantages are.
OBJECTIVES
To explore the scope of the scientific research on the use of digital technology related to men's sexual disorders and to analyze the primary sources of digital information related to this field.
ACQUISITION OF EVIDENCE
Systematic searches of the scientific literature, websites (10 first results in each google search) and mobile applications (apps). The searches combined the keywords "web" and "app" with "erectile dysfunction", "premature ejaculation", "Peyronie", "male hypogonadism", and "infertility". Websites and apps were assessed for quality according to predefined indicators.
SYNTHESIS OF EVIDENCE
The qualitative analysis of the scientific literature included 116 manuscripts; 47% were clinical studies based on online survey, 9% dealt with digital treatments, 11% with quality/safety of digital healthcare environment, 3% with digital activity, 21% with patient empowerment, and 9% with online drug selling. Of 50 websites assessed for quality, 29 (58%) scored 4 or 5 on a 5-point Likert scale. The app search yielded 40 apps; only 3 of them (8%) reported the identity of a health center or healthcare professional involved.
CONCLUSIONS
Patients and healthcare professionals may benefit from digital resources related to men's sexual disorders; however, a strong commitment by the scientific and healthcare community is essential to increase the quality of these resources.
PubMed: 29102483
DOI: 10.1016/j.acuro.2017.05.008 -
World Journal of Urology Dec 2017To clarify the efficacy of phosphodiesterase-5 inhibitors (PDE5Is) and selective serotonin reuptake inhibitors (SSRIs) in men with premature ejaculation (PE). (Review)
Review
PURPOSE
To clarify the efficacy of phosphodiesterase-5 inhibitors (PDE5Is) and selective serotonin reuptake inhibitors (SSRIs) in men with premature ejaculation (PE).
METHODS
We searched the PubMed, Embase, and Cochrane Library databases to identify all randomized, controlled trials (RCTs) and compared the results, including intravaginal ejaculation latency time, satisfaction, intercourse per-week and side effects after treatment with PDE5I or SSRIs versus placebo, combined use of PDE5I with SSRIs versus PDE5I or SSRIs alone, and PDE5I versus SSRIs for treating PE.
RESULTS
The study inclusion criteria were met by 23 studies (ten RCTs with five crossover studies) involving 6145 patients. The data synthesized from these studies indicated that the efficacy of PDE5Is and SSRIs was better than that of placebo (p < 0.00001; p < 0.00001); however, more patients had side effects while taking PDE5Is and SSRIs (p < 0.00001; p < 0.00001). The efficacy of the combined treatment was significantly better than that of PDE5Is or SSRIs alone (p < 0.00001; p < 0.00001); however, more patients had side effects from the combined treatment than from SSRIs (p = 0.0002), with no significant difference in PDE5Is (p = 0.5). The efficacy of PDE5Is was better than that of SSRIs (p = 0.006), and no significant difference was observed in the frequency of side effects (p = 0.93).
CONCLUSIONS
PDE5Is were significantly more effective than placebo or SSRIs for treating PE, while SSRIs were better than placebo. The combined treatment had better efficacy than PDE5Is or SSRIs alone.
Topics: Humans; Male; Phosphodiesterase 5 Inhibitors; Premature Ejaculation; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 28913588
DOI: 10.1007/s00345-017-2086-5 -
European Urology Focus Feb 2017Phosphodiesterase type 5 inhibitors (PDE5-Is) are prescribed off-label for the treatment of premature ejaculation (PE). (Meta-Analysis)
Meta-Analysis
CONTEXT
Phosphodiesterase type 5 inhibitors (PDE5-Is) are prescribed off-label for the treatment of premature ejaculation (PE).
OBJECTIVE
To systematically review the evidence from randomised controlled trials (RCTs) for PDE5-Is in the management of PE.
EVIDENCE ACQUISITION
Medline and other databases were searched through September 2015. Quality of RCTs was assessed. Intravaginal ejaculatory latency time (IELT) data were pooled in a meta-analysis. Heterogeneity was assessed.
EVIDENCE SYNTHESIS
Fifteen RCTs were included. The majority were of unclear methodological quality. Pooled IELT evidence suggests that PDE5-Is are significantly more effective than placebo (231 participants, p<0.00001), that there is no difference between PDE5-Is and selective serotonin reuptake inhibitors (SSRIs; 405 participants, p=0.50), and that PDE5-Is combined with an SSRI are significantly more effective than SSRIs alone (521 participants, p=0.001); however, high levels of statistical heterogeneity are evident (I ≥ 40%). Single-RCT evidence suggests that sildenafil is significantly more effective than the squeeze technique, but both lidocaine gel and tramadol are significantly more effective than sildenafil. Sildenafil combined with behavioural therapy is significantly more effective than behavioural therapy alone. Sexual satisfaction and ejaculatory control appear to be better with PDE5-Is compared with placebo and with PDE5-Is combined with an SSRI compared with an SSRI alone. Adverse events are reported with both PDE5-Is and other agents.
CONCLUSIONS
PDE5-Is are significantly more effective than placebo and PDE5-Is combined with an SSRI are significantly more effective than SSRIs alone at increasing IELT and improving other effectiveness outcomes; however, heterogeneity is evident across RCTs. The methodological quality of the majority of RCTs is unclear.
PATIENT SUMMARY
We reviewed phosphodiesterase type 5 inhibitors (PDE5-Is) for treating premature ejaculation. We found evidence to suggest that PDE5-Is are effective compared with placebo and that PDE5-Is combined with an SSRI are more effective than an SSRI alone. Adverse events are reported with PDE5-Is and other agents; however, the quality of the evidence is uncertain.
TRIAL REGISTRATION
PROSPERO registration number CRD42013005289.
Topics: Drug Therapy, Combination; Humans; Male; Phosphodiesterase 5 Inhibitors; Premature Ejaculation; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 28720356
DOI: 10.1016/j.euf.2016.02.001 -
Andrologia Mar 2018We attempted to evaluate whether circumcision has an effect on premature ejaculation. We searched three databases: PubMed, EMBASE and Google scholar on 1 May 2016 for... (Meta-Analysis)
Meta-Analysis Review
We attempted to evaluate whether circumcision has an effect on premature ejaculation. We searched three databases: PubMed, EMBASE and Google scholar on 1 May 2016 for eligible studies that referred to male sexual function after circumcision. No language restrictions were imposed. The Cochrane Collaboration's RevMan 5.2 software was employed for data analysis, and the fixed or the random-effect model was selected depending on the heterogeneity. Twelve studies were included in the meta-analysis, containing a total of 10019 circumcised and 11570 uncircumcised men. All studies were divided into five subgroups by types of study design to evaluate the effect of circumcision on premature ejaculation (PE). Intravaginal ejaculation latency time (IELT), difficulty of orgasm, erectile dysfunction (ED) and pain during intercourse were also assessed because PE was usually discussed along with these subjects. There were no significant differences in PE (odds ratio [OR], 0.90; 95% confidence interval (CI), 0.72-1.13; p = .37) and orgasm (OR, 1.04; 95% CI, 0.89-1.21; p = .65) between circumcised and uncircumcised group. However, IELT (OR, 0.72; 95% CI, 0.60-0.83; p < .00001), ED (OR, 0.42;95% CI, 0.22-0.78; p = .40) and pain during intercourse (OR, 0.36; 95% CI, 0.17-0.76; p = .007) favoured circumcised group. Based on these findings, circumcision does not have effect on PE.
Topics: Adult; Age Factors; Circumcision, Male; Coitus; Humans; Infant; Male; Orgasm; Pain; Premature Ejaculation; Surveys and Questionnaires
PubMed: 28653427
DOI: 10.1111/and.12851 -
Complementary and Alternative Medicine for Management of Premature Ejaculation: A Systematic Review.Sexual Medicine Mar 2017Premature ejaculation (PE) is defined as ejaculation within 1 minute (lifelong PE) or 3 minutes (acquired PE), inability to delay ejaculation, and negative personal... (Review)
Review
INTRODUCTION
Premature ejaculation (PE) is defined as ejaculation within 1 minute (lifelong PE) or 3 minutes (acquired PE), inability to delay ejaculation, and negative personal consequences. Management includes behavioral and pharmacologic approaches.
AIM
To systematically review effectiveness, safety, and robustness of evidence for complementary and alternative medicine in managing PE.
METHODS
Nine databases including Medline were searched through September 2015. Randomized controlled trials evaluating complementary and alternative medicine for PE were included.
MAIN OUTCOME MEASURES
Studies were included if they reported on intravaginal ejaculatory latency time (IELT) and/or another validated PE measurement. Adverse effects were summarized.
RESULTS
Ten randomized controlled trials were included. Two assessed acupuncture, five assessed Chinese herbal medicine, one assessed Ayurvedic herbal medicine, and two assessed topical "severance secret" cream. Risk of bias was unclear in all studies because of unclear allocation concealment or blinding, and only five studies reported stopwatch-measured IELT. Acupuncture slightly increased IELT over placebo in one study (mean difference [MD] = 0.55 minute, P = .001). In another study, Ayurvedic herbal medicine slightly increased IELT over placebo (MD = 0.80 minute, P = .001). Topical severance secret cream increased IELT over placebo in two studies (MD = 8.60 minutes, P < .001), although inclusion criteria were broad (IELT < 3 minutes). Three studies comparing Chinese herbal medicine with selective serotonin reuptake inhibitors (SSRIs) favored SSRIs (MD = 1.01 minutes, P = .02). However, combination treatment with Chinese medicine plus SSRIs improved IELT over SSRIs alone (two studies; MD = 1.92 minutes, P < .00001) and over Chinese medicine alone (two studies; MD = 2.52 minutes, P < .00001). Adverse effects were not consistently assessed but where reported were generally mild.
CONCLUSION
There is preliminary evidence for the effectiveness of acupuncture, Chinese herbal medicine, Ayurvedic herbal medicine, and topical severance secret cream in improving IELT and other outcomes. However, results are based on clinically heterogeneous studies of unclear quality. There are sparse data on adverse effects or potential for drug interactions. Further well-conducted randomized controlled trials would be valuable.
PubMed: 28041925
DOI: 10.1016/j.esxm.2016.08.002