Geometric Mean Intravaginal Ejaculatory Latency Time Research Articles

(184) A Novel, On-demand Therapy for Lifelong Premature Ejaculation using a Miniature Trans-Perineal Electrical Stimulator, the vPatch - a Randomized Controlled Trial

Abstract Introduction While Premature Ejaculation (PE) is a common and disturbing sexual dysfunction in men, currently available treatment modalities have limited efficacy and low treatment adherence. In this study, we assessed perineal Transcutaneous Electrical Stimulation (TES) as a new possibility to treat (PE) Objective To assess the feasibility, safety, and efficacy of vPatch, a miniaturized on-demand perineal (TES) device, for treating PE. Methods We designed a bi-center, international, prospective, randomized, double-blind, two-arm, sham-controlled, first-in-human, clinical study. Calculating for statistical power, 59 patients 21-56 (mean 39.8+9.28) y/o with lifelong PE were included. During the initial visit, intravaginal ejaculatory latency time (IELT) was measured over a 2-week run-in period. Eligibility was confirmed in Visit 2, based on IELT values, and medical/sexual history. Eligible patients tried the vPatch to determine the individualized sensory and motor activation thresholds. Patients were randomized to Active (vPatch) and Sham device groups in a 2:1 ratio. During Visit 3, IELTs, Clinical Global Impression of Change (CGIC) scores, and Premature Ejaculation Profile (PEP) questionnaire outcomes were recorded. The vPatch device safety profile was determined by comparing the incidence of treatment-emergent adverse events. Primary endpoints assessed: 1. vPatch device efficacy as mean fold change in geometric mean IELT; each person was compared to themselves, with and without the device, and the Sham group was compared to the Active Group. 2. vPatch safety profile. Secondary endpoints assessed changes in (PEP) before and after treatment and last visit (CGIC) scores. Results Of 59 patients, 51 completed the study, 34 in Active and 17 in Sham Group. The baseline geometric mean IELT significantly increased from 67 to 123 seconds (p<0.0001) in the Active Group, as compared to increasing insignificantly from 63 to 81 seconds (p=0.1653) in the Sham Group. IELT significantly increased by 3.22-fold in the Active as compared to the Sham group (p=0.0047). Geometric mean time fold increases of IELT in Active compared to the Sham group were 1.7 (95% CI 1.5-2.1) vs. 1.2 (95% CI 1.0-1.6), respectively. No serious adverse events were reported. According to the CGIC, patients in the active group were significantly more satisfied with the treatment (74% vs. 41%, p=0.0274). The subjects in the active arm reported significant improvement in all 4 PEP parameters (P<0.05). Conclusions We demonstrated the possibility to treat lifelong PE by prolonging coitus on-demand, using electric stimulation of ejaculation muscles with vPatch. This treatment may potentially become an on-demand, non-invasive, and drug-free treatment for PE. Disclosure Yes, this is sponsored by industry/sponsor: Virility LTD, Israel Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Virility LTD, Israel.

A novel, on-demand therapy for premature ejaculation using a miniature trans-perineal electrical stimulator: a randomized-controlled trial

<h3>Objectives</h3> To assess the feasibility, safety, and efficacy of a miniaturized on-demand perineal Transcutaneous Electrical Stimulation (TES) Using the vPatch device, for the treatment of premature ejaculation (PE). <h3>Methods</h3> We designed a bi-center, international, prospective, randomized, double-blind, sham-controlled, clinical study. A total of 59 lifelong PE patients were included. After the screening visit (Visit 1), patients measured their intravaginal ejaculatory latency time (IELT) for a 2-week run-in period and complete the Premature Ejaculation Profile (PEP) questionnaire. At Visit 2, eligible patients tried vPatch to determine the individualized sensory and motor activation thresholds. Patients were randomized into active and sham arms in a 2:1 ratio. At Visit 3, the IELT values and PEP outcomes were recorded again. Clinical Global Impression of Change (CGIC) scores were noted. <h3>Results</h3> Of the patients, 51 completed the study, 34 in the active and 17 in the sham arm. In the active arm the Baseline Geometric Mean IELT (BGMI) was 67 seconds (s) and significantly increased by 56s (standard error (SE) 9s) to 123s (p<.0001). However, in the sham arm the BGMI was 63s and increased insignificantly by 17s (SE 12s) to 80s (p=0.1653). The increase in IELT from base line was 3.22-fold greater in favor of the active arm (p=0.0047). In the active arm 91% (31/34) of the subjects significantly improved their IELT due to treatment compared to baseline. The mean geometric time-fold in IELT, in those positive responders was 2.04 (CI 95% 1.68-2.4). According to the CGIC, patients in the active group were significantly more satisfied with the treatment (74% vs. 41%, p=0.0274). The subjects in the active arm reported significant improvement in all 4 PEP parameters (P<0.05). <h3>Conclusions</h3> IELT values and patient-reported outcome measures can be improved with TES using vPatch. This treatment may become an on-demand, noninvasive, and drug-free therapeutic option for lifelong PE. <h3>Conflicts of Interest</h3> This study was sponsored by Virility Medical Ltd

LBA02-11 NOVEL ON-DEMAND TREATMENT FOR LIFELONG PREMATURE EJACULATION USING TRANSCUTANEOUS PERINEAL MINI-PATCH STIMULATOR

You have accessJournal of UrologyCME1 May 2022LBA02-11 NOVEL ON-DEMAND TREATMENT FOR LIFELONG PREMATURE EJACULATION USING TRANSCUTANEOUS PERINEAL MINI-PATCH STIMULATOR Ariki Shechter, Nicola Mondaini, Ege Can Serefoglu, Tal Gollan, Boaz Appel, and Ilan Gruenwald Ariki ShechterAriki Shechter More articles by this author , Nicola MondainiNicola Mondaini More articles by this author , Ege Can SerefogluEge Can Serefoglu More articles by this author , Tal GollanTal Gollan More articles by this author , Boaz AppelBoaz Appel More articles by this author , and Ilan GruenwaldIlan Gruenwald More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002670.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Background: Premature Ejaculation (PE) is a prevalent sexual dysfunction in men. Available treatments demonstrate limited efficacy and low treatment adherence. Objectives: To assess feasibility, safety, and efficacy of the Mini-patch, an on-demand transcutaneous perineal electrical stimulator, for the treating of PE. METHODS: Design, Setting, and Participants: Bi-center, international, prospective, randomized, double-blind, two-arm, sham-controlled, clinical study. After screening, intravaginal ejaculatory latency time (IELT) of candidates was measured. Eligibility was based on IELT values and medical/sexual history. Patients were randomized to Active and Sham device groups in a 2:1 ratio. Device safety profile was determined by incidence of treatment-emergent adverse events comparison. Outcome Measurements and Statistical Analysis: Clinical Global Impression of Change (CGIC) scores, Premature Ejaculation Profile (PEP) questionnaire outcomes, and Mini-patch safety profile. Statistical power was calculated. Primary endpoints assessed device efficacy by mean fold change in geometric mean IELT (Mini-patch vs. sham treatment compared to baseline values). Adjusted mean difference for treatments, adjusted treatment effects (Mini-patch – sham), 95% confidence intervals (CI), and 2-sided P values were obtained. RESULTS: Of 59 patients randomized, 51 completed the study: 34 in the Active and 17 in the Sham arm. Baseline geometric mean IELT was 67 seconds and significantly increased to 123 seconds (p<0.0001) in the Active group, compared to 63 seconds increasing insignificantly to 81 seconds (p=0.1653) in the Sham group. The IELT significantly increased by 3.22-fold in the Active as compared to the Sham group (p=0.0047). Overall Geometric Mean Time Fold increases of IELT in the Active compared to the Sham group were 1.7 (95% CI 1.5-2.1) vs. 1.2 (95% CI 1.0-1.6), respectively. No serious adverse events were reported. CONCLUSIONS: Mini-patch has the potential to become a leading on-demand, noninvasive, and drug-free treatments for PE. Source of Funding: Virility Medical Ltd; Hod-hasharon, Israel © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1045 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ariki Shechter More articles by this author Nicola Mondaini More articles by this author Ege Can Serefoglu More articles by this author Tal Gollan More articles by this author Boaz Appel More articles by this author Ilan Gruenwald More articles by this author Expand All Advertisement PDF DownloadLoading ...

Objective and Subjective Measures of Premature Ejaculation: How Closely Do They Correspond and How Well Are the Subjective Measures Recalled?

BackgroundClinical trials evaluating new treatments for premature ejaculation (PE) should ideally include both objective end points and patient reported outcomes (PROs), but there is no consensus currently over the optimal measures or combination of outcomes. In addition, many PROs use a 1-month recall period, despite concerns about potential recall bias. AimsData from a clinical trial of men with lifelong PE were used to examine the consistency of 2 core items of the Premature Ejaculation Profile (PEP), a widely used PRO for assessing subjective aspects of PE. The specific aim was to assess the level of agreement between the original 1-month recall version compared with a new event-based version of the scale in men meeting current definitions of lifelong PE. A further aim was to investigate the convergent validity between an objective end point of intravaginal ejaculatory latency time (IELT), subjective PEP responses, and a patient's Clinical Global Impression of Change (CGIC) measure. MethodsFor assessment of consistency of PEP responses (short-term [ie, sexual event driven] vs 1-month recall), descriptive statistics, correlation coefficients (Pearson and Spearman), and Bland-Altman plots are presented for each time interval. For assessment of convergent validity, descriptive statistics and correlation coefficients (Pearson and Spearman) are presented for each assessment with geometric mean IELT values. Results are also depicted graphically. Geometric mean IELT over the last 4 weeks of treatment and change from baseline (absolute and fold change) were estimated via a general linear model for each category of change in PEP and CGIC, adjusting for baseline IELT. OutcomesPEP items administered via 1-month recall and short-term event-driven responses gave virtually identical results. There was a strong correlation (very good convergent validity) between IELT and responses to PEP and the CGIC. Clinical translationMen with lifelong PE can accurately recall their level of sexual functioning over the previous month. The PEP and CGIC are appropriate instruments to measure the subjective response of men with PE to new treatments. Strengths and limitationsOur analyses address gaps in previously published research on PE assessment methodology. Men with acquired PE, men without partners, and men in homosexual relationships were not studied. ConclusionsIn a clinical trial setting, PEP and CGIC are appropriate end points and are likely the optimal combination of PROs for use with IELT to enable a global assessment of patient response to new PE treatments.Althof S, Rosen R, Harty B, et al. Objective and Subjective Measures of Premature Ejaculation: How Closely Do They Correspond and How Well Are the Subjective Measures Recalled? J Sex Med 2020;17:634–644.

Somatosensory evoked potentials assess the efficacy of circumcision for premature ejaculation.

To assess the efficacy and mechanism of circumcision in the treatment of premature ejaculation (PE) with redundant prepuce, we enrolled a total of 81 PE patients who received circumcision. The patients' ejaculatory ability and sexual performances were evaluated before and after circumcision by using questionnaires (Intravaginal ejaculation latency time (IELT), Chinese Index of PE with 5 questions (CIPE-5) and International Index of Erectile function- 5 (IIEF-5)). Furthermore, somatosensory evoked potentials (SEPs) including dorsal nerve (DNSEP) and glans penis (GPSEP) of the patients were also measured. The mean IELTs of preoperation and post operation were 1.10±0.55 and 2.48±2.03 min, respectively (P<0.001). In addition, the geometric mean IELT after operation was 2.16 min, compared with the baseline 1.07 min before the operation, the fold increase of the IELT was 2.02. Compared with the uncircumcised status, scores of CIPE-5 showed a significant increase after circumcision (P<0.001). The mean latencies (and amplitudes) of GPSEP and DNSEP were 38.1±4.0 ms (3.0±1.9 uV) and 40.5±3.4 ms (2.8±1.6 uV) before circumcision, respectively; and 42.8±3.3 ms (2.8±1.6 uV) and 40.5±4.1 ms (2.4±1.2 uV) in the follow-up end point after circumcision. Only the latencies of GPSEP showed significant prolongation before and after circumcision (P<0.001). The ejaculation time improvement after circumcision is so small, and equal to placebo response, therefore it could not be interpreted as a therapeutic method in men with PE.

Retraction statement: Analysis of association between the 5-HTTLPR and STin2 polymorphisms in the serotonin-transporter gene and clinical response to a selective serotonin reuptake inhibitor (sertraline) in patients with premature ejaculation.

Study Type – Therapy (cohort) Level of Evidence 2b OBJECTIVE To test the hypothesis that polymorphism within the gene-linked polymorphic region (5-HTTLPR) and second intron of SLC6A4 gene (STin2) is associated with selective serotonin-reuptake inhibitors (SSRIs) response in subjects with premature ejaculation (PE). PATIENTS AND METHODS In all, 246 men with PE were recruited in this study. They were asked to take sertraline 50 mg daily for 2 weeks, and thereafter 100 mg daily, for a 12-week treatment period. Pretreatment evaluation included history and physical examination, intravaginal ejaculatory latency time (IELT), and International Index of Erectile Function (IIEF). The efficacy of treatment was assessed using responses to IIEF, and geometric mean IELT evaluation. 5-HTTLPR was genotyped using polymerase chain reaction techniques. A repeated-measures analysis of variance of geometric mean IELT was done to test a genotype effect on treatment outcome with SSRI (sertraline). RESULTS Of 227 participants who completed the study, 175 (77.1%) responded to sertraline (IELT >1 min). Overall the patients had a 3.7-fold (95% confidence interval, CI, 1.72–5.46) increase of the geometric mean IELT (P = 0.001). The results showed that responses were significantly better for the LA/LA genotype of the 5-HTTLPR polymorphism than for S-allele carriers (P = 0.001). The STin2 12/12 genotype was found more often in those responding to sertraline than in those not responding (P = 0.001). The probability of patients responding sufficiently to sertraline with an LA/LA genotype was highest (odds ratio 4.66, 95% CI, 2.48–6.14). CONCLUSIONS These findings indicate that the genotype of 5-HTT contributes in unique ways to the variation in the outcome of PE treatment with SSRIs.

Nonresponders to daily paroxetine and another SSRI in men with lifelong premature ejaculation: a pharmacokinetic dose-escalation study for a rare phenomenon.

PurposeNonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetine treatment in men with lifelong premature ejaculation (PE) who were also known to be nonresponders to other SSRIs.Materials and MethodsFive males with lifelong PE who were known nonresponders to paroxetine and other serotonergic antidepressants and eight males with lifelong PE who were specifically recruited were included. Blood sampling occurred 1 month and 1 day before the start of treatment and at the end of three consecutive series of 4 weeks of daily treatment with 10-, 20-, and 30-mg paroxetine, respectively. Blood samples for measurement of leptin and paroxetine were taken at 8:30 AM, 9:30 AM, 10:30 AM, and 11:30 AM, respectively. At 9:00 AM, one tablet of 10-, 20-, or 30-mg paroxetine was taken during the first, second, and third month, respectively. Intravaginal ejaculatory latency time (IELT) was measured with a stopwatch. The main outcome measures were the fold increase in the geometric mean IELT, serum leptin and paroxetine concentrations, body mass index (BMI), 5-HT1A receptor C-1019G polymorphism, and CYP2D6 mutations.ResultsBetween the 7 paroxetine responders and 6 nonresponders, the fold increase in the geometric mean IELT was significantly different after daily 10-mg (p=0.003), 20-mg (p=0.002), and 30-mg paroxetine (p=0.026) and ranged from 2.0 to 8.8 and from 1.1 to 1.7, respectively. BMI at baseline and at the end of the study was not significantly different between responders and nonresponders. Serum leptin levels at baseline were similar in responders and nonresponders and did not change during treatment. The serum paroxetine concentration increased with increasing dosage and was not significantly different between responders and nonresponders. There was no association between the fold increase in the geometric mean IELT and serum paroxetine levels during the three treatment periods nor between leptin levels during the treatment periods and serum paroxetine levels. For the 5-HT1A receptor C-1019G variation, all responders had the CC genotype and all nonresponders had the GC genotype, respectively.ConclusionsComplete absence of paroxetine-induced ejaculation delay is presumably related to pharmacodynamic factors and perhaps to 5-HT1A receptor gene polymorphism.

The 5-HT2C receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation.

It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2C receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2C receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2C receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2C receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9 s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10–20, 20–30 and 30–60 s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2C receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes (Cys/Cys) is significantly lower (22.6 s; 95% CI 18.3–27.8 s) than in male homozygous mutants (Ser/Ser) (40.4 s; 95% CI 20.3–80.4 s) (P = 0.03). It is concluded that Cys23Ser 5-HT2C receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

Comparison Between On-Demand Dosing of Dapoxetine Alone and Dapoxetine Plus Mirodenafil in Patients with Lifelong Premature Ejaculation: Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study

There is partial evidence to support the use of phophodiesterase-5 inhibitor (PDE5-I) for the treatment of premature ejaculation (PE). We compared on-demand dosing of dapoxetine alone and combined with mirodenafil in subjects with lifelong PE and without erectile dysfunction (ED). Our prospective, randomized, double-blind, placebo-controlled, multicenter trial enrolled 118 subjects with lifelong PE without ED. PE was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision. Patients were divided into two groups: dapoxetine 30 mg plus placebo (group A, n=56) and dapoxetine 30 mg plus mirodenafil 50 mg (group B, n=62). During 12 weeks, intravaginal ejaculatory latency time (IELT) and the time from foreplay to beginning intercourse (FTIT) with a stopwatch, and Premature Ejaculation Profile (PEP) were measured. Overall sexual act time (OSAT; sum of FTIT and IELT) was calculated. Any treatment-emergent adverse events (TEAEs) were also recorded. Over 12 weeks, IELT, OSAT, and PEP index score significantly improved in group B compared with group A (increased geometric mean IELT in group A and B=3.6 and 6.1 minutes, P=0.026; increased geometric mean OSAT in group A and B=5.5 and 9.9 minutes, P=0.012; increased median PEP index score in group A and B=1.0 and 1.3, P=0.046). However, there was no significant difference between two groups with respect to improvement of FTIT (P=0.147). TEAEs did not differ between groups (all P>0.05), and there was no serious adverse event in any subjects. Low dose of dapoxetine combined with mirodenafil showed better results in terms of IELT, OSAT, and PEP index score, and similar TEAEs, compared with that of dapoxetine only. Our results support the suggestion that the PDE5-Is have a potential role in the treatment of PE without ED.

The Diagnostic Value of the Premature Ejaculation Diagnostic Tool and Its Association with Intravaginal Ejaculatory Latency Time

Premature ejaculation (PE) is the most prevalent male ejaculation disorder. The premature ejaculation diagnostic tool (PEDT) was developed to systematically apply the DSM-IV-TR criteria in diagnostic PE. To evaluate the diagnostic value of the PEDT and its association with intravaginal ejaculatory latency time (IELT). (i) Korean validation of PEDT: data was collected from men interviewed by one of the two clinical experts, who made a diagnostic of present or absence of PE, using DSM-IV-TR criteria. A total of 103 patients with PE and 100 men without PE were enrolled into the study and requested to complete the PEDT; and (ii) The correlation between IELT and PEDT: 200 participants were enrolled and each participant was asked to make out PEDT. All participants were requested to measure IELT. Validity and reliability of the PEDT and its association with IELT. The geometric mean IELT of the PE group was 115.37 ± 78.14 seconds. The number of men reporting IELTs of <1, 1 to ≤ 2, and >2 minutes were 28 (28.6%), 29 (29.6%), and 41 (41.8%), respectively. The Cronbach's alpha score was calculated as 0.93, showing adequate internal consistency. The test-retest correlation coefficients of each item were higher than 0.72 and the correlation coefficients of the total score was 0.88. (P < 0.001) Sensitivity and specificity analyses suggested a score of ≤ 8 indicated no PE, 9 and 10 probable PE, and ≥ 11 PE. The PEDT total score and IELT showed an adequate negative correlation. (ρ = -0.77, P < 0.0001) also, the PEDT total score of the PE subgroup (IELT ≤ 2 minutes) and IELT showed a negative correlation. (ρ = -0.6, P < 0.0001) The PEDT was highly effective in detecting the presence of PE. The result of our study supports its validity as a diagnostic tool in the clinical setting.

Analysis of association between the 5‐HTTLPR and STin2 polymorphisms in the serotonin‐transporter gene and clinical response to a selective serotonin reuptake inhibitor (sertraline) in patients with premature ejaculation

To test the hypothesis that polymorphism within the gene-linked polymorphic region (5-HTTLPR) and second intron of SLC6A4 gene (STin2) is associated with selective serotonin-reuptake inhibitors (SSRIs) response in subjects with premature ejaculation (PE). In all, 246 men with PE were recruited in this study. They were asked to take sertraline 50 mg daily for 2 weeks, and thereafter 100 mg daily, for a 12-week treatment period. Pretreatment evaluation included history and physical examination, intravaginal ejaculatory latency time (IELT), and International Index of Erectile Function (IIEF). The efficacy of treatment was assessed using responses to IIEF, and geometric mean IELT evaluation. 5-HTTLPR was genotyped using polymerase chain reaction techniques. A repeated-measures analysis of variance of geometric mean IELT was done to test a genotype effect on treatment outcome with SSRI (sertraline). Of 227 participants who completed the study, 175 (77.1%) responded to sertraline (IELT >1 min). Overall the patients had a 3.7-fold (95% confidence interval, CI, 1.72-5.46) increase of the geometric mean IELT (P = 0.001). The results showed that responses were significantly better for the L(A)/L(A) genotype of the 5-HTTLPR polymorphism than for S-allele carriers (P = 0.001). The STin2 12/12 genotype was found more often in those responding to sertraline than in those not responding (P = 0.001). The probability of patients responding sufficiently to sertraline with an L(A)/L(A) genotype was highest (odds ratio 4.66, 95% CI, 2.48-6.14). These findings indicate that the genotype of 5-HTT contributes in unique ways to the variation in the outcome of PE treatment with SSRIs.

Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation.

Premature ejaculation (PE) is thought to be the most common male sexual dysfunction; however, the prevalence of lifelong (LL)-PE is relatively low. The aim of this study was to investigate the effects of on-demand vardenafil (10 mg) to modify the intravaginal ejaculatory latency time (IELT) in men with LL-PE without erectile dysfunction. Forty-two men (18-35 years) were enrolled in a 16-week, double-blind, placebo-controlled, cross-over study. Primary end point was the modification from baseline of IELT assessed by stopwatch technique; secondary end points were post-ejaculatory refractory time (PERT) and variations of scores at the Index of Premature Ejaculation questionnaire. The changes in geometric mean IELT were superior after taking vardenafil (0.6+/-0.3 vs 4.5+/-1.1 min, P<0.01), compared with placebo (0.7+/-0.3 vs 0.9+/-1.0 min, ns). PERT dropped significantly after vardenafil (16.7+/-2.0 vs 4.3+/-0.9 min, P<0.001), compared with placebo (15.3+/-2.2 vs 15.8+/-2.3 min). Patients who took vardenafil (vs placebo) reported significantly (P<0.01) increased ejaculatory control (6+/-2 vs 16+/-2), improved overall sexual satisfaction (7+/-2 vs 15+/-1) and distress (4+/-1 vs 8+/-1) scores, respectively. Multiple regression analysis (r(2)=0.86) for IELT by the number of attempts at sexual intercourse showed significant differences between the slopes of lines for placebo and vardenafil (P<0.0001). The most common adverse events for vardenafil (vs placebo) were headache (10 vs 3%), flushing (12 vs 0%) and dyspepsia (10 vs 0%), which tended to disappear over the time. In conclusion, in our study, vardenafil increased IELT and reduced PERT in men with LL-PE. Besides, improvements in confidence, perception of ejaculatory control and overall sexual satisfaction were reported.

PSD502 improves ejaculatory latency, control and sexual satisfaction when applied topically 5 min before intercourse in men with premature ejaculation: results of a phase III, multicentre, double‐blind, placebo‐controlled study

To determine the effect of PSD502 applied topically 5 min before intercourse on the Index of Premature Ejaculation (IPE) and intravaginal ejaculatory latency time (IELT) of men with lifelong premature ejaculation (PE) defined according to the International Society of Sexual Medicine (ISSM) definition; secondary objectives were to evaluate the safety and tolerability of PSD502 in patients with PE, and their sexual partners. Men aged >18 years, in stable heterosexual, monogamous relationships, and with lifelong PE diagnosed according to both the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (text revision) criteria and the ISSM definition, consented (together with their partners) to enter the baseline period of the study. Patients who documented an IELT of <or=1 min with two or more of the first three sexual encounters during the 4-week baseline period were randomized, in a 2:1 ratio, to receive double-blind treatment with PSD502 (three actuations of spray each containing 7.5 mg lidocaine and 2.5 mg prilocaine applied 5 min before intercourse) or placebo for 3 months. Patients completed IPE and Premature Ejaculation Profile (PEP) questionnaires at entry and at monthly clinic visits, and recorded stopwatch-timed IELT during each sexual encounter. Patients rated the quality of their orgasms on a 5-point scale at baseline and at the end of the treatment period, and rated the study medication on a 4-point scale. Safety was assessed by collecting adverse event data. In all, 300 men with PE were randomized from 31 centres in Europe. The geometric mean (range) IELT over the 3-month treatment period increased from a baseline of 0.6 min in both groups to 3.8 (0.3-57.8) and 1.1 (0-15.0) min in the PSD502 and placebo groups, respectively. Adjusting for treatment-group imbalances, this represents a 6.3-fold and 1.7-fold increase in adjusted geometric means. There were significantly greater increases in the scores for the IPE domains of ejaculatory control and sexual satisfaction in the PSD502 group than in the placebo group, with a mean (sem) 7.0 (0.59)-point difference between treatments in change from baseline in the IPE domain for ejaculatory control and a 5.9 (0.57)- point difference in change from baseline in the IPE domain for sexual satisfaction (both P < 0.001). This was supported by improvements in all secondary endpoints. At the end of the treatment period 66% of patients rated PSD502 as 'good' or 'excellent'. PSD502 was well tolerated and no systemic adverse events were reported. Localized treatment-related adverse events were reported by 2.6% and 3.1% of patients and partners, respectively. PSD502 applied topically 5 min before intercourse improved ejaculatory latency and significantly improved ejaculatory control and sexual satisfaction, factors relevant for acceptance of a PE treatment by both patient/physician and regulatory authorities. PSD502 was well tolerated by both patients and partners, with no systemic side-effects and a low incidence of localized effects, and was rated favourably by most users. PSD502 therefore appears to offer significant advantages over other therapies in development for the treatment of PE.

ORIGINAL RESEARCH—EJACULATORY DISORDERS: Screening for Erectile Dysfunction in Men with Lifelong Premature Ejaculation—Is the Sexual Health Inventory for Men (SHIM) Reliable?

ABSTRACT Introduction Some men with premature ejaculation (PE) and normal erectile function record contradictory response/s to The Sexual Health Inventory for Men (SHIM) and may be incorrectly categorized as suffering from erectile dysfunction (ED). Aims The aim of this study was to evaluate the frequency of false positive SHIM diagnosis of ED in men with lifelong PE. Main Outcome Measures SHIM, stopwatch intravaginal ejaculation latency time (IELT). Methods A prospective observational study of men with normal erectile function and lifelong PE, diagnosed using the ISSM definition of lifelong PE, was conducted. The SHIM was self-administered at Visit 1. Mean per subject stopwatch IELT was determined from four subsequent intercourse attempts. Results Seventy-eight subjects with a mean age of 33.2 ± 8.3 years and a geometric mean IELT of 15.9 ± 2.3 seconds were enrolled. The mean SHIM score for all subjects was 20.4 ± 6.0. Fifty-two subjects (66.7%) have SHIM scores of &amp;gt;21 (mean 24.3 ± 1.1), consistent with normal erectile function, and a geometric mean IELT of 18.3 ± 2.2 seconds. Twenty-six subjects (33.3%) had SHIM scores &amp;lt;22 (mean 12.7 ± 3.7), consistent with a false positive diagnosis of ED, and a geometric mean IELT of 10.5 ± 2.3 seconds. The incidence of false positive SHIM diagnosis of ED (SHIM &amp;lt; 22) was inversely related to the IELT. Although the geometric mean IELT for subjects with SHIM scores &amp;lt;22 was significantly less than that of all subjects and subjects with SHIM scores &amp;gt;21, there were no significant differences between the geometric mean IELT or the IELT distribution of all subjects vs. the normal erectile function IELT (SHIM &amp;gt; 21) cohort. Conclusion This study demonstrates a 33.3% false positive SHIM diagnosis of ED in men with PE. This is likely to limit subject recruitment in clinical trials by exclusion of subjects with low-range IELTs but is unlikely to result in significantly different baseline IELTs or IELT distributions.

Dapoxetine for the Treatment of Premature Ejaculation: Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial in 22 Countries

BackgroundDapoxetine is being developed for the on-demand treatment of premature ejaculation (PE). Previous clinical trials have demonstrated its safety and efficacy. ObjectiveTo evaluate the long-term efficacy and safety of dapoxetine in men with PE. Design, setting, and participantsThis randomized, double-blind, parallel-group, placebo-controlled, phase 3 trial, conducted in 22 countries, enrolled men (N=1162) ≥18 yr of age who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE for ≥6 mo, with an intravaginal ejaculatory latency time (IELT) ≤2min in ≥75% of intercourse episodes at baseline. InterventionDapoxetine 30mg or dapoxetine 60mg or placebo on demand (1–3h before intercourse) for 24 wk. MeasurementsStopwatch-measured IELT, Premature Ejaculation Profile (PEP), Clinical Global Impression (CGI) of change, adverse events (AEs). Results and limitationsThe study was completed by 618 men. Mean average IELT increased from 0.9min at baseline (all groups) to 1.9min, 3.2min, and 3.5min with placebo and dapoxetine 30mg and dapoxetine 60mg, respectively, at study end point; geometric mean IELT increased from 0.7min at baseline to 1.1min, 1.8min, and 2.3min, respectively, at study end point. All PEP measures and IELTs improved significantly with dapoxetine versus placebo at week 12 and week 24 (p<0.001 for all). The most common AEs were nausea, dizziness, diarrhea, and headache. AEs led to discontinuation in 1.3%, 3.9%, and 8.2% of subjects with placebo and dapoxetine 30mg and dapoxetine 60mg, respectively. Limitations of this study included the exclusion of men who were not in long-term monogamous relationships. ConclusionsDapoxetine significantly improved all aspects of PE and was generally well tolerated in this broad population.

Turkish validation of the premature ejaculation diagnostic tool and its association with intravaginal ejaculatory latency time

There are uncertain issues on the diagnostic methods of premature ejaculation (PE). The premature ejaculation diagnostic tool (PEDT) was developed to systematically apply the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria in diagnosing PE and the aim of this study is to carry out the Turkish validation of the PEDT and to evaluate its association with intravaginal ejaculatory latency time (IELT). A total of 94 patients with a self-reported complaint of PE and 88 men without PE were enrolled into the study and requested to complete the nine-item PEDT, which was translated into Turkish. The patients were also requested to measure IELT. All participants were requested to come for a second visit to assess the PEDT's retest reliability; data from 78 men in the PE group and 69 men in the control group were collected. The IELT data of 35 patients were also recorded. The mean age of the PE group and the control group were 39.4+/-9.7 (24-65) and 30.1+/-5.7 (20-56), respectively, (P=0.068). Among the patients in the PE group, 24 (68.5%) reported life-long PE, whereas 11 (31.5%) reported acquired PE. The geometric mean IELT of the PE group was 59.7+/-46.2 (6.5-197.7) s. The number of men reporting IELTs of <1, 1-<2 and >2 min were 20 (57.1%), 11 (31.5) and 4 (11.4%), respectively. The factor analysis assessment showed that the five-item combination (questions 1, 2, 3, 4 and 8) explained 74.4% of the variance, there were no other combinations that explained the variance more effectively. Cronbach's alpha score of five-item combination was calculated as 0.77, showing adequate internal consistency. The overall Cronbach's alpha score did not increase if any item combination was deleted. The test-retest correlation coefficients of each item were higher than 0.80 and the correlation coefficient of the total score was 0.90. The PEDT and IELT showed an adequate correlation (rho=0.44). As a conclusion, the validated five-item Turkish version of PEDT is a reliable questionnaire to screen PE among Turkish patients. Its significant association with IELT supports the fact that PEDT may be of benefit for the diagnosis of PE and measuring the response to treatment. In addition, PEDT seems to be more applicable than measuring IELT in our population, for the assessment of PE.

Premature Ejaculation and Pharmaceutical Company-Based Medicine: The Dapoxetine Case

The manufacturer of dapoxetine funded randomized clinical trials to study its effect in premature ejaculation (PE). Financial support by pharmaceutical companies, however, may jeopardize the neutrality of clinical research. To investigate the scientific process that has been followed in dapoxetine treatment trials and reviews as compared to daily drug treatment trials and reviews with selective serotonin reuptake inhibitors (SSRIs) in men with PE. A search of Medline and Embase was conducted using the search terms "dapoxetine" or "SSRI." References of retrieved articles were searched. Only studies describing the use of these drugs in men with PE were included. Main Outcome Measures. Compared fold-increase intravaginal ejaculation latency time (IELT), geometric mean IELT, and adverse effect profiles between dapoxetine and SSRIs in PE. Preclinical studies on dapoxetine, including a multicenter study (category A) and reviews (category B), were compared with clinical studies with daily conventional SSRIs in PE (category C). Categories A/B focused on patient-reported outcomes with less attention for the IELT. The ejaculation-delaying effect of dapoxetine was expressed as natural mean IELT rather than as geometrical mean IELT. Dapoxetine side effects were monthly scored. In contrast, a significant part of category C articles focused on IELT data, used geometric mean IELT outcomes, and one study reported the side effects measured 24-48 hours after drug intake using a validated questionnaire. Without the Food and Drug Administration approval, dapoxetine, as well as other SSRIs in PE, is an off-label drug for PE. However, the off-label use of dapoxetine has never been criticized by clinical investigators in contrast to commentaries against the off-label use of daily SSRI treatment in PE. Manufacturer-funded drug treatment research (categories A and B) is advantageously treated by some authors as compared with nonfunded trials with daily conventional SSRIs (category C). PE drug treatment research is a young and dynamic field, and its development deserves transparency to its development.

Geometric Mean IELT and Premature Ejaculation: Appropriate Statistics to Avoid Overestimation of Treatment Efficacy

The intravaginal ejaculation latency time (IELT) behaves in a skewed manner and needs the appropriate statistics for correct interpretation of treatment results. To explain the rightful use of geometrical mean IELT values and the fold increase of the geometric mean IELT because of the positively skewed IELT distribution. Linking theoretical arguments to the outcome of several selective serotonin reuptake inhibitor and modern antidepressant study results. Geometric mean IELT and fold increase of geometrical mean IELT. Log-transforming each separate IELT measurement of each individual man is the basis for the calculation of the geometric mean IELT. A drug-induced positively skewed IELT distribution necessitates the calculation of the geometric mean IELTs at baseline and during drug treatment. In a positively skewed IELT distribution, the use of the "arithmetic" mean IELT risks an overestimation of the drug-induced ejaculation delay as the mean IELT is always higher than the geometric mean IELT. Strong ejaculation-delaying drugs give rise to a strong positively skewed IELT distribution, whereas weak ejaculation-delaying drugs give rise to (much) less skewed IELT distributions. Ejaculation delay is expressed in fold increase of the geometric mean IELT. Drug-induced ejaculatory performance discloses a positively skewed IELT distribution, requiring the use of the geometric mean IELT and the fold increase of the geometric mean IELT.

Safety and efficacy of venlafaxine in the treatment of premature ejaculation: a double-blind, placebo-controlled, fixed-dose, randomised study

Venlafaxine is a serotonin-noradrenaline reuptake inhibitor antidepressant. Two hundred and twenty-two married men (mean age, 34 years) with premature ejaculation (PE) were randomly assigned to receive 75 mg of venlafaxine extended release (n = 112) (group 1) or placebo (n = 110) (group 2) for 12 weeks. Pre-treatment evaluation included history and physical examination, geometric mean intravaginal ejaculatory latency time (IELT) and International Index of Erectile Function (IIEF). The efficacy of two treatments was assessed every 2 weeks during treatment, and at the end of study, using responses to IIEF, IELT evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and adverse drug effects. At the end of treatment period, the geometric mean IELT in venlafaxine and placebo group demonstrated 1.7-fold (95% CI: 0.76-1.96) and 1.6-fold (95% CI: 0.87-1.84) increase respectively (P = 0.1). The mean weekly intercourse episodes increased from pre-treatment values of 1.2 and 1.18 to 2.1 and 1.9 for venlafaxine and placebo respectively (P = 0.08). Baseline mean intercourse satisfaction domain values of IIEF 12 and 12 reached to 13 and 12 at 12-week treatment in groups 1 and 2 respectively (P = 0.07). Mean number of adverse events was 32 for venlafaxine and 8 for placebo (P = 0.02). Venlafaxine is not better than placebo in treatment of PE.