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Arab Journal of Urology 2021To analyse the current therapeutic options for patients with premature ejaculation (PE) and highlight their mechanism(s) of action, effectiveness, advantages and... (Review)
Review
To analyse the current therapeutic options for patients with premature ejaculation (PE) and highlight their mechanism(s) of action, effectiveness, advantages and limitations. A literature search was conducted using the PubMed database searching for articles exploring different PE treatment modalities. A Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) approach was used to report the results of the literature search. A total of 149 articles were included in this review. The currently available treatment methods for PE include behavioural therapy, local anaesthetics, tricyclic antidepressants, selective serotonin reuptake inhibitors, and selective phosphodiesterase inhibitors. Most PE treatments are either experimental or used off-label. New treatments are certainly warranted to overcome this exasperating sexual dysfunction. AIPE: Arabic Index of Premature Ejaculation; CNS: central nervous system; CYP: cytochrome P450; ED: erectile dysfunction; FDA: United States Food and Drug Administration; H1: histamine receptors; 5-HT: 5-hydroxytryptamine; IELT: The intravaginal ejaculation latency time; IPE: Index of Premature Ejaculation; M1: muscarinic receptors; OCD: obsessive-compulsive disorder; PDE5: phosphodiesterase type 5; PE: premature ejaculation; PEP: Premature Ejaculation Profile; PRO: patient-reported outcome; RCT: randomised controlled trial; SS: Severance Secret (cream); SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants.
PubMed: 34552780
DOI: 10.1080/2090598X.2021.1943273 -
Health Technology Assessment... Mar 2015Premature ejaculation (PE) is commonly defined as ejaculation with minimal sexual stimulation before, on or shortly after penetration and before the person wishes it. PE... (Review)
Review
BACKGROUND
Premature ejaculation (PE) is commonly defined as ejaculation with minimal sexual stimulation before, on or shortly after penetration and before the person wishes it. PE can be either lifelong and present since first sexual experiences (primary), or acquired (secondary), beginning later (Godpodinoff ML. Premature ejaculation: clinical subgroups and etiology. J Sex Marital Ther 1989;15:130-4). Treatments include behavioural and pharmacological interventions.
OBJECTIVE
To systematically review evidence for clinical effectiveness of behavioural, topical and systemic treatments for PE.
DATA SOURCES
The following databases were searched from inception to 6 August 2013 for published and unpublished research evidence: MEDLINE; EMBASE; Cumulative Index to Nursing and Allied Health Literature; The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects and the Health Technology Assessment database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science. The US Food and Drug Administration website and the European Medicines Agency (EMA) website were also searched.
METHODS
Randomised controlled trials (RCTs) in adult men with PE were eligible (or non-RCTs in the absence of RCTs). RCT data were extrapolated from review articles when available. The primary outcome was intravaginal ejaculatory latency time (IELT). Data were meta-analysed when possible. Other outcomes included sexual satisfaction, control over ejaculation, relationship satisfaction, self-esteem, quality of life, treatment acceptability and adverse events (AEs).
RESULTS
A total of 103 studies (102 RCTs, 65 from reviews) were included. RCTs were available for all interventions except yoga. The following interventions demonstrated significant improvements (p < 0.05) in arithmetic mean difference in IELT compared with placebo: topical anaesthetics - eutectic mixture of local anaesthetics (EMLA(®), AstraZeneca), topical eutectic mixture for PE (Plethora Solutions Ltd) spray; selective serotonin reuptake inhibitors (SSRIs) - citalopram (Cipramil(®), Lundbeck), escitalopram (Cipralex(®), Lundbeck), fluoxetine, paroxetine, sertraline, dapoxetine (Priligy(®), Menarini), 30 mg or 60 mg; serotonin-noradrenaline reuptake inhibitors - duloxetine (Cymbalta(®), Eli Lilly & Co Ltd); tricyclic antidepressants - inhaled clomipramine 4 mg; phosphodiesterase-5 (PDE5) inhibitors - vardenafil (Levitra(®), Bayer), tadalafil (Cialis(®), Eli Lilly & Co Ltd); opioid analgesics - tramadol (Zydol SR(®), Grünenthal). Improvements in sexual satisfaction and other outcomes compared with placebo were evident for SSRIs, PDE5 inhibitors and tramadol. Outcomes for interventions not compared with placebo were as follows: behavioural therapies - improvements over wait list control in IELT and other outcomes, behavioural therapy plus pharmacotherapy better than either therapy alone; alpha blockers - terazosin (Hytrin(®), AMCO) not significantly different to antidepressants in ejaculation control; acupuncture - improvements over sham acupuncture in IELT, conflicting results for comparisons with SSRIs; Chinese medicine - improvements over treatment as usual; delay device - improvements in IELT when added to stop-start technique; yoga - improved IELT over baseline, fluoxetine better than yoga. Treatment-related AEs were evident with most pharmacological interventions.
LIMITATIONS
Although data extraction from reviews was optimised when more than one review reported data for the same RCT, the reliability of the data extraction within these reviews cannot be guaranteed by this assessment report.
CONCLUSIONS
Several interventions significantly improved IELT. Many interventions also improved sexual satisfaction and other outcomes. However, assessment of longer-term safety and effectiveness is required to evaluate whether or not initial treatment effects are maintained long term, whether or not dose escalation is required, how soon treatment effects end following treatment cessation and whether or not treatments can be stopped and resumed at a later time. In addition, assessment of the AEs associated with long-term treatment and whether or not different doses have differing AE profiles is required.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013005289.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adult; Anesthetics, Local; Behavior Therapy; Humans; Male; Phosphodiesterase 5 Inhibitors; Premature Ejaculation; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 25768099
DOI: 10.3310/hta19210 -
Sexual Medicine Jun 2023Although acupuncture is widely used to treat premature ejaculation (PE), its effectiveness remains highly controversial. (Review)
Review
BACKGROUND
Although acupuncture is widely used to treat premature ejaculation (PE), its effectiveness remains highly controversial.
AIM
To evaluate the efficacy and safety of acupuncture on PE.
METHODS
According to the relevant keywords, 11 major English and Chinese databases were searched for randomized controlled trials (RCTs) of acupuncture alone or in combination with other treatments for PE. The quality of evidence across studies was assessed by the GRADEpro tool.
OUTCOMES
Study outcome measures included the intravaginal ejaculation latency time (IELT), the Premature Ejaculation Diagnostic Tool (PEDT), the Chinese Index of Premature Ejaculation-5 (CIPE-5), treatment success rate, and adverse events.
RESULTS
Seven trials were included in this review for a total of 603 participants. A low quality of evidence suggests that it is not possible to determine whether acupuncture, as compared with a selective serotonin reuptake inhibitor, has an advantage in improving the IELT (standardized mean difference [SMD], -1.75; 95% CI, -6.12 to 2.63; = .43, = 98%), PEDT scores (SMD, 0.32; 95% CI, -0.68 to 1.32; = .53, = 85%), and treatment success rate (risk ratio, 0.69; 95% CI, 0.41-1.14; = .15). However, participants receiving acupuncture had a lower CIPE-5 (SMD, -1.06; 95% CI, -1.68 to -0.44; < .01). As compared with sham acupuncture, acupuncture significantly improved the IELT (SMD, 1.47; 95% CI, 1.01-1.92; < .01, = 0%) and PEDT scores (SMD, -1.23; 95% CI, -1.78 to -0.67; < .01, = 37%). When compared with other treatments alone, a combined treatment with acupuncture can significantly improve the IELT (SMD, 7.06; 95% CI, 2.53-11.59; < .01, = 97%), CIPE-5 (SMD, 0.84; 95% CI, 0.45-1.22; < .01, = 0%), and treatment success rate (SMD, 1.60; 95% CI, 1.18-2.16; < .01, = 53).
CLINICAL IMPLICATIONS
The results suggest a significant effect of acupuncture in the treatment of certain important indicators of PE; however, this finding needs to be treated with caution because of the quality of the RCTs included.
STRENGTHS AND LIMITATIONS
Comprehensive inclusion of available RCTs has been performed. However, limitations include a low number of studies and a lack of detailed information to allow subgroup analysis.
CONCLUSION
The present systematic review and meta-analysis show that acupuncture has a significant effect on several subjective PE parameters, such as improving the feeling of control over ejaculation and distress, particularly when used in an integrated way. However, due to the low quality of evidence, acupuncture still needs larger well-designed RCTs to be confirmed.
PubMed: 37397031
DOI: 10.1093/sexmed/qfad034 -
Cureus Aug 2023This meta-analysis was conducted to assess the effectiveness of topical anesthetics in preventing premature ejaculation. We conducted an online database search for... (Review)
Review
This meta-analysis was conducted to assess the effectiveness of topical anesthetics in preventing premature ejaculation. We conducted an online database search for original studies comparing topical anesthetic agents with placebo in patients with premature ejaculation. After selecting relevant articles, we extracted data on baseline characteristics and predetermined endpoints. Intravaginal ejaculatory latency time (IELT) was the primary outcome for efficacy. Mean differences and corresponding 95% confidence intervals were used to present continuous data. A random-effects model was used to pool the data, and subgroup analysis was performed based on the type of anesthetic agent used. Eleven randomized controlled trials were examined, involving a total of 2008 participants. After analyzing the combined results, it was found that Severance Secret (SS) cream (CJ CheilJedang Corporation, Seoul, South Korea) demonstrated significantly higher effectiveness than a placebo in increasing IELT (P = 0.001). Similarly, the topical eutectic mixture for premature ejaculation (TEMPE), lidocaine, and the eutectic mixture of local anesthetics (EMLA) were significantly more efficient than a placebo (P<0.00001; P = 0.0001; P<0.00001). Additionally, it was found that lidocaine gel was more efficient than paroxetine or sildenafil (P = 0.04; P<0.00001). In conclusion, topical anesthetics increase IELT in men with premature ejaculation more effectively than placebo, sildenafil, tadalafil, paroxetine, and dapoxetine.
PubMed: 37664322
DOI: 10.7759/cureus.42913 -
Efficacy of Various Treatment in Premature Ejaculation: Systematic Review and Network Meta-Analysis.The World Journal of Men's Health Apr 2024To investigate the various strategies used for the treatment of premature ejaculation (PE); these encompassed behavioral, drug and surgical interventions.
PURPOSE
To investigate the various strategies used for the treatment of premature ejaculation (PE); these encompassed behavioral, drug and surgical interventions.
MATERIALS AND METHODS
We retrieved data from electronic literature searches of PubMed and Cochrane library using the MeSH (Medical Subject Headings terms) and text keywords from the earliest available date of indexing through September 2022. The subject headings and text keywords included those related to the population (male patients with PE), interventions & comparisons (mono and combination treatment), and outcomes (ejaculation latency time, ELT).
RESULTS
The initial search identified a total of 454 articles from electronic databases. Finally, a total of 10,474 patients from 59 direct comparison trials were included 143 effect sizes with 43 treatments. Of these, 9 of mono treatments and 4 of combination treatments were statistically significant. Pharmaceutical agents commonly used for patients with PE are prescribed off-label, except for dapoxetine. The surface under the cumulative ranking curve values of ranking probabilities for each treatment performance, which indicated that tramadol 100 mg ranked first in terms of ELT.
CONCLUSIONS
Medications recommended by the American Urological Association and the Sexual Medicine Society of North America were all incorporated within the present review, together with additional management approaches that have been evaluated in randomized controlled trials. The findings indicated that in addition to SSRIs, tramadol, clomipramine, topical agents and PDE5 inhibitors could be used in the therapy of PE.
PubMed: 37635338
DOI: 10.5534/wjmh.230030 -
American Journal of Men's Health 2022Premature ejaculation (PE) is one of the major causes of sexual dysfunction. Levosulpiride is an off-label medicine used to treat PE, but no review on its efficacy... (Meta-Analysis)
Meta-Analysis Review
Premature ejaculation (PE) is one of the major causes of sexual dysfunction. Levosulpiride is an off-label medicine used to treat PE, but no review on its efficacy exists. A systematic review and meta-analysis was performed to determine the efficacy of levosulpiride in treating PE. Databases PubMed, Science Direct, and Google Scholar were searched. Randomized control trials (RCTs) comparing levosulpiride with placebo or other medicine were selected. Odds ratio (OR) of improved intravaginal ejaculation latency time (IELT) was calculated. A total of 97 articles were retrieved from database search, of which only four RCTs containing 203 men met the selection criteria. All four RCTs were included in systematic review while only two were included in meta-analysis. A high selection and detection bias was found in both of these studies. Meta-analysis also showed the odds of improving IELT in PE patients using levosulpiride to be significantly higher ( < .05) compared with those who used placebo, OR: 100.81, 95% confidence interval (CI) [13.12-774.90], = 0%. Odds of improving IELT for > 5 min (500% improvement) were also significantly higher ( < .05) compared with the placebo groups (OR: 38.88, 95% CI [5.12-295.29], = 0%). The odds of improving IELT for > 1 min, but < 5 min were also significantly higher ( < .05) than placebo groups (OR: 32.84, 95% CI [4.15-259.75], = 0%). Levosulpiride improved IELT, but even so, limited studies are available on this topic. Additional research is thus required to support the present review's findings.
Topics: Ejaculation; Humans; Male; Premature Ejaculation; Sulpiride; Treatment Outcome
PubMed: 36154321
DOI: 10.1177/15579883221124832 -
Sexual Health Apr 2016Eutectic Mixture of Local Anaesthetics (EMLA) is recommended for use off-label as a treatment for premature ejaculation (PE). Other topical anaesthetics are available,... (Meta-Analysis)
Meta-Analysis Review
Eutectic Mixture of Local Anaesthetics (EMLA) is recommended for use off-label as a treatment for premature ejaculation (PE). Other topical anaesthetics are available, some of which have been evaluated against oral treatments. The purpose of this systematic review was to evaluate the evidence from randomised controlled trials (RCTs) for topical anaesthetics in the management of PE. Bibliographic databases including MEDLINE were searched to August 2014. The primary outcome was intra-vaginal ejaculatory latency time (IELT). Methodological quality of RCTs was assessed. IELT and other outcomes were pooled across RCTs in a meta-analysis. Between-trial heterogeneity was assessed. Nine RCTs were included. Seven were of unclear methodological quality. Pooled evidence (two RCTs, 43 participants) suggests that EMLA is significantly more effective than placebo at increasing IELT (P<0.00001). Individual RCT evidence also suggests that Topical Eutectic-like Mixture for Premature Ejaculation (TEMPE) spray and lidocaine gel are both significantly more effective than placebo (P=0.003; P<0.00001); and lidocaine gel is significantly more effective than sildenafil or paroxetine (P=0.01; P=0.0001). TEMPE spray is associated with significantly more adverse events than placebo (P=0.003). More systemic adverse events are reported with tramadol, sildenafil and paroxetine than with lidocaine gel. Diverse methods of assessing sexual satisfaction and ejaculatory control with topical anaesthetics are reported and evidence is conflicting. Topical anaesthetics appear more effective than placebo, paroxetine and sildenafil at increasing IELT in men with PE. However, the methodological quality of the existing RCT evidence base is uncertain.
Topics: Anesthetics, Local; Humans; Male; Premature Ejaculation; Randomized Controlled Trials as Topic
PubMed: 26599522
DOI: 10.1071/SH15042 -
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 -
Medicine Aug 2016Premature ejaculation (PE) is the most prevalent male sexual dysfunction. Epidemiologic findings are inconsistent concerning the risk for depression associated with PE. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Premature ejaculation (PE) is the most prevalent male sexual dysfunction. Epidemiologic findings are inconsistent concerning the risk for depression associated with PE.
OBJECTIVE
The aim of this study was to investigate the potential association between between depression and risk of PE.
DATA SOURCES
We conducted a literature search of PubMed, Embase, and the Cochrane Library from these databases' inception through June 2014 for observational epidemiological studies examining the association between depression on risk of PE.
STUDY ELIGIBILITY CRITERIA
Studies were selected if they reported the risk estimates for PE associated with depression.
PARTICIPANTS
patients>18 years of age suffering from PE.
INTERVENTIONS
a history of depressive disorder.
STUDY APPRAISAL AND SYNTHESIS METHODS
These odds ratios (ORs) were pooled using a random or fixed effects model and were tested for heterogeneity. Subgroup analysis was employed to explore heterogeneity.
RESULTS
Eight trials involving 18,035 patients were included in the meta-analysis. Depression were statistically significantly associated with the risk of PE (OR = 1.63, 95% CI:1.42-1.87). There was no evidence of between-study heterogeneity (P = 0.623, I = 0.0%). The association was similar when stratified by mean age, geographical area, study design, sample size, publication year, and controlling key confounders.
LIMITATIONS
The severity of depression and PE could not be identified due to unavailable data of trials. No evidence of publication bias was observed.
CONCLUSIONS
These findings provide evidence that depression is associated with a significantly increased risk of PE. In addition, more prospective studies are necessary to evaluate the association and identify the ideal treatment.
SYSTEMATIC REVIEW REGISTRATION NUMBER
CRD42016041272.
Topics: Depression; Humans; Male; Premature Ejaculation; Risk Factors
PubMed: 27583879
DOI: 10.1097/MD.0000000000004620 -
BMC Urology Jan 2015Tramadol is a centrally acting analgesic prescribed off-label for the treatment of premature ejaculation (PE). However, tramadol may cause addiction and difficulty in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tramadol is a centrally acting analgesic prescribed off-label for the treatment of premature ejaculation (PE). However, tramadol may cause addiction and difficulty in breathing and the beneficial effect of tramadol in PE is yet not supported by a high level of evidence. The purpose of this study was to systematically review the evidence from randomised controlled trials (RCT) for tramadol in the management of PE.
METHODS
We searched bibliographic databases including MEDLINE to August 2014 for RCTs. The primary outcome was intra-vaginal ejaculatory latency time (IELT). Methodological quality of RCTs was assessed. Between-group differences in IELT and other outcomes were pooled across RCTs in a meta-analysis. Statistical and clinical between-trial heterogeneity was assessed.
RESULTS
A total of eight RCTs that evaluated tramadol against a comparator were included. The majority of RCTs were of unclear methodological quality due to limited reporting. Pooled evidence (four RCTs, 721 participants), suggests that tramadol is significantly more effective than placebo at increasing IELT over eight to 12 weeks (p = 0.0007). However, a high level of statistical heterogeneity is evident (I-squared = 74%). Single RCT evidence indicates that tramadol is significantly more effective than paroxetine taken on-demand, sildenafil, lidocaine gel, or behavioural therapy on IELT in men with PE. Tramadol is associated with significantly more adverse events including: erectile dysfunction, constipation, nausea, headache, somnolence, dry mouth, dizziness, pruritus, and vomiting, than placebo or behavioural therapy over eight to 12 weeks of treatment. However, addiction problems or breathing difficulties reported by patients for PE is not assessed in the current evidence base.
CONCLUSIONS
Tramadol appears effective in the treatment of PE. However, these findings should be interpreted with caution given the observed levels of between-trial heterogeneity and the reporting quality of the available evidence. The variability across placebo-controlled trials in terms of the tramadol dose evaluated and the treatment duration does not permit any assessment of a safe and effective minimum daily dose. The long-term effects and side effects, including addiction potential, for men with PE have not been evaluated in the current evidence base.
TRIAL REGISTRATION
The review is registered on PROSPERO 2013: CRD42013005289 .
Topics: Drug Administration Schedule; Evidence-Based Medicine; Humans; Male; Off-Label Use; Orgasm; Patient Satisfaction; Premature Ejaculation; Prevalence; Randomized Controlled Trials as Topic; Tramadol; Treatment Outcome
PubMed: 25636495
DOI: 10.1186/1471-2490-15-6