An Internally Validated Nomogram for Predicting the Likelihood of Improvement of Clinical Global Impression in Patients With Lifelong Premature Ejaculation Treated With Dapoxetine

BackgroundAlthough the introduction of dapoxetine has ushered in a new era in the treatment of premature ejaculation, many patients with lifelong premature ejaculation (LPE) exhibit an unimproved clinical global impression even after treatment with dapoxetine.AimTo investigate independent predictors of the improvement of Clinical Global Impression (iCGI) in patients with LPE treated with dapoxetine and develop a nomogram to predict a patient's likelihood of achieving iCGI.MethodsData of 243 patients with LPE diagnosed at Xijing Hospital (Xi'an, China) and Northwest Women's and Children's Hospital (Xi'an, China) from January 2019 to May 2020 were analyzed. Independent predictors of iCGI were identified, and a nomogram was developed using R software based on a multivariate logistic regression model. The predictive accuracy of the nomogram was measured using the area under the receiver operating characteristic curve. The nomogram was calibrated by comparing predictions with observations.Main Outcome MeasuresThe primary outcome was the patient-rated Clinical Global Impression of Change scale score after a 4-week course of dapoxetine treatment, which was collected via an online questionnaire. A Clinical Global Impression of Change score of ≥1 was defined as iCGI in this study.ResultsPatients with LPE with at least a bachelor's degree, a self-reported intravaginal ejaculation latency time of >1 minute, and an International Index of Erectile Function question 5 score of ≥3 were independent factors associated with achieving iCGI, whereas a Premature Ejaculation Diagnostic Tool question 1 score of ≥2 was an independent factor negatively associated with achieving iCGI. The predictive accuracy of the nomogram, which was developed by integrating all variables with independent predictive significance, was 0.710 (95% confidence interval: 0.702–0.718). In addition, the calibration plot demonstrated excellent agreement between predictions and observations.Clinical ImplicationsIf the predictive performance of our nomogram is further proven in multiple external validations, it can be used to select suitable patients for dapoxetine treatment, thereby reducing the number of patients discontinuing treatment.Strengths & LimitationsThis study developed the first nomogram for predicting the likelihood of achieving iCGI in patients with LPE treated with dapoxetine. However, our nomogram was not externally validated using independent cohorts from other institutions.ConclusionThis study identified several independent predictors of iCGI in patients with LPE treated with dapoxetine. An effective nomogram was developed to predict their likelihood of achieving iCGI. External validations using data of Western patients with LPE are required to test the broader applicability of this Chinese patient-based tool.Hou G, Gao M, Zhang L, et al. An Internally Validated Nomogram for Predicting the Likelihood of Improvement of Clinical Global Impression in Patients With Lifelong Premature Ejaculation Treated With Dapoxetine. J Sex Med 2020;17:2341–2350.     

Bulbocavernosus Reflex to Stimulation of Prostatic Urethra in Patients with Lifelong Premature Ejaculation

IntroductionLifelong premature ejaculation (LPE) is a prevalent sexual dysfunction among men, while its precise pathologic mechanisms have remained poorly understood.AimIn our study, the correlation between excitability of bulbocavernosus reflex (BCR) to stimulation of the prostatic urethra and LPE was studied.MethodsTwenty normal potent male volunteers and 42 patients with LPE were studied by inserting a specially designed Foley catheter with two electrodes mounted on its distal surface (intraurethral catheter electrode) into bladder to evoke the BCR to stimulation of prostatic urethra. Also, sensitivity of glans penis to electrical stimulation was detected by two surface electrodes.Main Outcome MeasuresSensory thresholds of BCR to stimulation of prostatic urethra, thresholds to evoke stable BCR, latencies of BCR, and sensory thresholds of glans penis to electrical stimulation.ResultsThe mean sensory thresholds of BCR to stimulation of prostatic urethra, thresholds to evoke stable BCR, latencies of BCR, and sensory thresholds of glans penis were 12.38 ± 3.71 mA (0.2 ms in duration,1 Hz), 23.81 ± 5.55 mA (0.2 ms, 1 Hz), 70.48 ± 6.33 ms, and 11.89 ± 2.26 mA (0.04 ms in duration,3 Hz) in the patients with LPE, respectively, and were 18.20 ± 2.68 mA (0.2 ms, 1 Hz), 34.76 ± 4.15 mA (0.2 ms, 1 Hz), 71.20 ± 5.77 ms, and 14.16 ± 1.94 mA (0.04 ms, 3 Hz) in the normal potent men, respectively (mean ± SD). Statistically significant differences were seen regarding the sensory thresholds of BCR to stimulation of prostatic urethra, the thresholds to evoke stable BCR and the sensory thresholds of glans penis between the two groups (P < 0.001). No statistically significant differences were seen regarding the latencies of BCR between the two groups (P > 0.05).ConclusionsPatients with LPE might have hyperexcitable BCR to stimulation of prostatic urethra, which is probably one of the important factors for its etiology. Zhou C, Jiang X, Xu Z, Guo L, Chen J, Wang H, Zhang D, and Shi B. Bulbocavernosus reflex to stimulation of prostatic urethra in patients with lifelong premature ejaculation.     

Content Validity of the Premature Ejaculation Profile,Original and Per-Event Formats,in Men with Lifelong Premature Ejaculation

Background

The Premature Ejaculation Profile (PEP) is a patient-reported outcome (PRO) measure that is widely used in clinical research in men with premature ejaculation (PE) but has not been fully validated for men meeting the current International Society for Sexual Medicine (ISSM) definition of lifelong PE.

Baseline Characteristics and Treatment Outcomes for Men with Acquired or Lifelong Premature Ejaculation with Mild or No Erectile Dysfunction: Integrated Analyses of Two Phase 3 Dapoxetine Trials

IntroductionPremature ejaculation (PE) is classified as an acquired or lifelong condition but data on baseline characteristics and response to treatment of men with acquired or lifelong PE and mild erectile dysfunction (ED) or normal erectile function (EF) is limited.AimTo present integrated analyses of baseline characteristics and treatment outcomes from phase 3 dapoxetine trials in men with acquired or lifelong PE and mild or no ED.MethodsData were analyzed from two randomized, double-blind, placebo-controlled, phase 3 clinical trials (International and Asia-Pacific) that evaluated efficacy and safety of dapoxetine (30 mg or 60 mg as needed [PRN]) in patients with PE. Men were ≥18 years, in a stable monogamous relationship for ≥6 months, met DSM-IV-TR criteria for PE for ≥6 months, had an International Index of Erectile Function EF domain score ≥21, and had an intravaginal ejaculatory latency time (IELT) ≤2 minutes in ≥75% of intercourse episodes.Main Outcome MeasuresDemographics, sexual history, and PE symptomatology at baseline, and mean IELT and patient-reported outcomes (PROs) at study end (week 12), were analyzed for men with acquired or lifelong PE and mild or no ED (EF score 21–25 vs. ≥26).ResultsBaseline characteristics except duration of PE were similar in men with acquired and lifelong PE, with no other differentiating features by ED status. Dapoxetine treatment improved significantly mean IELT (arithmetic and geometric) and PRO responses (perceived control over ejaculation, satisfaction with sexual intercourse, ejaculation-related personal distress, and interpersonal difficulty) for acquired and lifelong subtypes, but presence of mild ED diminished PRO responsiveness in both subtypes, particularly those with lifelong PE.ConclusionsBaseline characteristics and treatment outcomes were generally similar in men with acquired and lifelong PE. The presence of mild ED appears to be associated with a more modest treatment response, irrespective of lifelong or acquired PE subtype. Porst H, McMahon CG, Althof SE, Sharlip I, Bull S, Aquilina JW, Tesfaye F, and Rivas DA. Baseline characteristics and treatment outcomes for men with acquired or lifelong premature ejaculation with mild or no erectile dysfunction: Integrated analyses of two phase 3 dapoxetine trials.     

Bias in Evaluating Erectile Function in Lifelong Premature Ejaculation Patients with the International Index of Erectile Function—5

IntroductionLifelong premature ejaculation (LPE) is the most important ejaculating dysfunction. Relatively little is known about erectile function in this population.AimsWe attempted to evaluate the erectile function of patients with LPE using the International Index of Erectile Function—5 (IIEF-5) to determine if it is sufficiently reliable and accurate to make such an assessment.MethodsA total of 406 patients with LPE were enrolled in our study. The participants voluntarily answered the Premature Ejaculation Diagnostic Tool (PEDT) and IIEF-5 questionnaires and underwent a full history evaluation and clinical examination by doctors. Their answers were converted into data analyzed by a statistic software.Main Outcome MeasuresThe patients were diagnosed with LPE based on the diagnostic criteria and PEDT scores. The intravaginal ejaculation latency time was recorded according to patient self-reports. The IIEF-5 was used to evaluate their erectile function. Thorough history and clinical examination helped doctors make more correct diagnoses of erectile dysfunction (ED).ResultsOf the 406 patients, 70 (17.24%) patients had ED, as confirmed by doctors. IIEF-5 was accurate for the assessment of the erectile function of LPE patients when the cutoff was decreased to 15.5. Question 5 (1.34 ± 0.53) was the main reason for the drop in the total IIEF-5 score. Questions 1 and 5 shared low consistency with the other three IIEF-5 items, thus they lowered the reliability of the IIEF-5 scores. These questions created a confounding bias that decreased the diagnostic threshold of IIEF-5. However, they could not be removed from the IIEF-5 because they did not reduce its diagnostic accuracy in patients with LPE.ConclusionsBias from questions 1 and 5 lowered the reliability of the IIEF-5 scores; however, it did not reduce the diagnostic accuracy of the IIEF-5. The recommendation is to edit questions 1 and 5 when they are applied to populations with LPE. Tang Yuxin, Wang Yong, Zhu Haiyan, Jiang Xianzhen, Gan Yu, and Yang Jianfu. Bias in evaluating erectile function in lifelong premature ejaculation patients with the international index of erectile function—5.     

Anatomic Basis and Clinical Effect of Selective Dorsal Neurectomy for Patients with Lifelong Premature Ejaculation: A Randomized Controlled Trial

Introduction

Although guidelines from the American Urological Association and European Association of Urology do not consider surgical treatment for premature ejaculation (PE), the use of selective dorsal neurectomy (SDN) has increased for many years in Asian countries.

Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism is Associated with the Intravaginal Ejaculation Latency Time in Dutch Men with Lifelong Premature Ejaculation

IntroductionLifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 minute, and has been postulated as a neurobiological dysfunction with genetic vulnerability for the short IELTs, related to disturbances of central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission and 5-HT receptor functioning.AimTo investigate the relationship between 5-HT transporter gene-linked polymorphism (5-HTTLPR) and short IELTs in men with lifelong PE.MethodsA prospective study was conducted in 89 Dutch Caucasian men with lifelong PE. IELT during coitus was assessed by stopwatch over a 1-month period. Controls consisted of 92 Dutch Caucasian men. All men with LPE were genotyped for a 5-HTT-promoter polymorphism. Allele frequencies and genotypes of short (S) and long (L) variants of 5-HTTLPR polymorphism were compared between patients and controls. Association between LL, SL, and SS genotypes, and the natural logarithm of the IELT in men with LPE was investigated.Main Outcome MeasuresIELT measured by stopwatch, 5-HTTLPR polymorphism.ResultsIn men with lifelong PE, the geometric mean, median, and natural mean IELTs were 21, 26, and 32 seconds, respectively. There were no significant differences in the 5-HTT polymorphism alleles and genotypes between 89 Dutch Caucasian men with LPE (S 47%, L 53%/LL 29%, SL 48%, SS 22%) and 92 Dutch Caucasian controls (S 48%, L 52%/LL 29%, SL 45%, SS 26%). In men with lifelong PE there was a statistically significant difference between LL, SL, and SS genotypes in their geometric mean IELT (P ≤ 0.027); the LL genotypes had significantly shorter IELTs than the SS and SL genotypes.ConclusionsThe 5-HTTLPR polymorphism is associated with significant effects on the latency to ejaculate in men with lifelong PE. Men with SS and SL genotypes have 100% and 90% longer ejaculation time, respectively than men with LL genotypes. Janssen PKC, Bakker SC, Réthelyi J, Zwinderman AH, Touw DJ, Olivier B, and Waldinger MD. Serotonin transporter promoter region (5-HTTLPR) polymorphism is associated with the intravaginal ejaculation latency time in Dutch men with lifelong premature ejaculation.     

The Sympathetic Skin Response Located in the Penis as a Predictor of the Response to Sertraline Treatment in Patients with Primary Premature Ejaculation

IntroductionThe pathologic mechanisms of primary premature ejaculation (PPE) are complex and multifactorial, and hyperactivity of the sympathetic nervous system is one of the mechanisms.AimTo examine the effects of sertraline on sympathetic nervous system activity and assess the predictive value of the sympathetic skin response located in the penis (PSSR) on the response to sertraline treatment in PPE patients.MethodsSixty‐one patients with PPE were recruited. Each received 50 mg sertraline daily for 8 weeks. Before and after the experiment, the patients were evaluated for PSSR tests and sexual performance parameters. Additionally, based on the latency of PSSR, we divided the patients into a normal PSSR group and an abnormal PSSR group, and compared the sertraline treatment efficacy between the two groups.Main Outcome MeasuresChanges in intravaginal ejaculation latency time (IELT) and the Chinese premature ejaculation index‐5 (CIPE‐5), and the latencies and amplitudes of PSSR after sertraline treatment.ResultsOverall, 58 (95.1%) patients completed the entire study and were analyzed. After the 8‐week sertraline treatment, compared with those of pretreatment, IELT and CIPE‐5 scores were significantly increased (both P < 0.001), and the amplitudes and latencies of PSSR in the PPE patients were remarkably decreased and prolonged, respectively (both P < 0.001). In addition, the changes of the latencies of PSSR were positively correlated with the increment of IELT (r = 0.375, P = 0.004). The treatment outcome was better in patients with a baseline abnormal PSSR than in those with a baseline normal PSSR (P = 0.021).ConclusionsThese results suggest that clinical improvement in response to sertraline in the PPE patients, at least in part, is mediated through reducing sympathetic nervous system activity indexed by PSSR. Measurement of the PSSR appears to provide useful information for predicting treatment responses in the PPE patients. Xia J, Chen T, Chen J, Han Y, Xu Z, Zhou L, Chen Y, and Dai Y. The sympathetic skin response located in the penis as a predictor of the response to sertraline treatment in patients with primary premature ejaculation. J Sex Med 2014;11:2801–2808.     

他达那非治疗勃起功能障碍伴早泄患者的临床研究

目的:探讨他达那非治疗勃起功能障碍(ED)伴有早泄患者的临床疗效和安全性。方法:80例诊断为ED合并早泄患者,按每次服用他达那非20mg,共治疗12周。以阴道内射精潜伏期评价早泄治疗效果,并评估ED的总体疗效和治疗满意度,比较治疗前后的国际勃起功能指数评分5(IIEF-5)。结果:经过12周的治疗,早泄改善者共48例,有效率为60%。勃起功能改善者60例,总改善率为75%。不良反应共有10例(12.5%),均为轻度或中度,未经处理即自行缓解。结论:对ED合并早泄患者,他达那非能安全有效地改善其勃起功能,并能显著改善其早泄症状。     

Prevalence and Factors Associated with the Complaint of Premature Ejaculation and the Four Premature Ejaculation Syndromes: A Large Observational Study in China

IntroductionAlthough the new classification of premature ejaculation (PE) has been proposed by Waldinger et al., there have been few studies investigating the four PE syndromes in China.AimsWe investigated the prevalence and factors associated with the complaint of PE and the four PE syndromes in Anhui province, China.MethodsBetween September 2011 and September 2012, subjects were selected from five cities in Anhui province, China. They participated in this survey by completing a detailed verbal questionnaire regarding their demographic data and medical and sexual history. Men with PE complaint were diagnosed as lifelong PE (LPE), acquired PE (APE), natural variable PE (NVPE), or premature‐like ejaculatory dysfunction (PLED).Main Outcome MeasuresPE complaint was divided into four PE syndromes. Anxiety, depression, and erectile dysfunction were independently assessed by the self‐rating anxiety/depression scale and the international index of erectile function‐5, respectively.ResultsOf the 3,016 men evaluated, 25.80% complained of PE. The distribution of the four PE syndromes in men with PE complaint was in the order of NVPE (44.09%), PLPE (24.81%), APE (18.77%), and LPE (12.34%). Patients with PE complaint were older and more likely to smoke, had more comorbidities, and a higher body mass index (BMI) than patients without the complaint (P < 0.001 for all). Similar findings were also observed in patients with APE compared with other PE patients (depression P = 0.012, cardiovascular P = 0.003, others P < 0.001). In addition, the rates of counseling by a doctor in men with LPE and APE were higher than those in men with NVPE and PLED (P < 0.001).ConclusionThe prevalence of PE complaint in male population of Anhui province, China, was 25.80%, with the highest PE syndromes being NVPE and PLPE. Patients with PE complaint or APE were older and more likely to smoke, had more comorbidities, and a higher BMI. Gao J, Zhang X, Su P, Liu J, Xia L, Yang J, Shi K, Tang D, Hao Z, Zhou J, and Liang C. Prevalence and factors associated with the complaint of premature ejaculation and the four premature ejaculation syndromes: a large observational study in China. J Sex Med 2013;10:1874–1881.     

The Oxytocin Antagonist Cligosiban Prolongs Intravaginal Ejaculatory Latency and Improves Patient-Reported Outcomes in Men with Lifelong Premature Ejaculation: Results of a Randomized,Double-Blind,Placebo-Controlled Proof-of-Concept Trial (PEPIX)

IntroductionCligosiban is an orally administered oxytocin receptor antagonist being developed to treat premature ejaculation (PE).AimTo determine the safety and efficacy of cligosiban capsules (dose range 400–800 mg) to improve intravaginal ejaculation latency time (IELT) and patient-reported outcomes in men with severe lifelong PE.MethodsPatients recorded details of at least 4 sexual intercourse events during a 4-week run-in period, after which they underwent baseline assessments. Patients were eligible for the study if they rated their control of ejaculation as poor/very poor and their stopwatch-assessed IELT was ≤1 minute in ≥75% of intercourse attempts. Eligible patients were randomized to an 8-week treatment period with double-blind cligosiban or placebo (to be taken 1 to 6 hours prior to sexual activity). The starting dose was 400 mg (not more than 1 dose per day) which could be increased to 800 mg after 2 and/or 4 weeks of treatment. Assessments were conducted at 2, 4, and 8 weeks.Main Outcome MeasureEfficacy measures were comprised of IELT, self-rating of ejaculation control and ejaculation-related distress (recorded in an electronic diary after each intercourse attempt), premature ejaculation profile, and the Clinical Global Impression of Change.ResultsThe mean ratio of fold change from baseline in IELT to the last 4 weeks of treatment (cligosiban/placebo) was 1.9 compared to a baseline of 1.0 (P = .0079). The mean increase in IELT from baseline to the last 4 weeks of treatment was 61.0 seconds for cligosiban, which was significantly different from (and 3.6-fold greater than) the mean increase of 16.4 seconds for placebo (P = .0086). Statistically significant improvements in ejaculation control and ejaculation-related personal distress scores were also observed for cligosiban compared to little or no change with placebo. Cligosiban was generally well tolerated, with no serious or severe adverse events or other safety parameters.Clinical ImplicationsThis proof-of-concept study demonstrated the potential for cligosiban, an oxytocin antagonist, to successfully treat symptoms of severe lifelong PE.Strengths and LimitationsThis was a Phase II, randomized, double-blind, placebo-controlled study that was adequately powered to detect a clinically meaningful difference in change in IELT between cligosiban and placebo. Larger studies will be needed to confirm these findings, determine the optimal dose of cligosiban and assess efficacy in men with acquired PE.ConclusionsCligosiban was well tolerated, and resulted in significant benefits in both objective and subjective measures of ejaculatory control in men with lifelong PE and therefore offers significant potential as an on-demand, orally administered agent for the treatment of PE.McMahon C, Althof S, Rosen R, et al. The Oxytocin Antagonist Cligosiban Prolongs Intravaginal Ejaculatory Latency and Improves Patient-Reported Outcomes in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Trial (PEPIX). J Sex Med 2019; 16:1178–1187.     

The Oxytocin Antagonist Cligosiban Fails to Prolong Intravaginal Ejaculatory Latency in Men with Lifelong Premature Ejaculation: Results of a Randomized,Double-Blind,Placebo-Controlled Phase IIb trial (PEDRIX)

IntroductionCligosiban is an orally administered, centrally penetrant oxytocin receptor antagonist being developed to treat premature ejaculation (PE).AimTo determine the efficacy of 3 dose levels of cligosiban caplets to prolong intravaginal ejaculation latency time (IELT) and improve patient-reported outcomes in men with lifelong PE.MethodsPatients recorded details of at least 4 sexual intercourse events during a 4-week run-in period, after which they underwent baseline assessments. Patients were eligible for the study if their stopwatch-assessed IELT was ≤1 minute in ≥75% of intercourse attempts and if they met other diagnostic criteria for lifelong PE. Eligible patients (target 220 evaluable) were randomized to double-blind cligosiban 400, 800, or 1200 mg or matching placebo caplets (to be taken 1 to 6 hours prior to sexual activity). Assessments were conducted at 2, 4, and 8 weeks.Main Outcome MeasureEfficacy measures were comprised of IELT, self-rating of ejaculation control and ejaculation-related distress (recorded in an electronic diary after each intercourse attempt), premature ejaculation profile, Patient’s Global Impression of Severity, and the Clinical Global Impression of Change.ResultsThere were no clinically or statistically significant differences between cligosiban (at any dose level) and placebo for the primary endpoint (change in geometric IELT) or any of the secondary endpoints. Cligosiban was well tolerated with a side-effect profile similar to placebo.Clinical ImplicationsThis Phase IIb study failed to demonstrate the potential for cligosiban, an oxytocin antagonist, to successfully treat symptoms of severe lifelong PE at doses up to 1200 mg.Strengths and LimitationsThis was a Phase IIb, randomized, double-blind, placebo-controlled study that was adequately powered but failed to detect a clinically meaningful or statistical difference in change in IELT between cligosiban at 3 dose levels and placebo. This is in contrast to a similarly designed proof-of-concept study where cligosiban was flexibly dosed at doses up to 800 mg and did demonstrate clinically meaningful and statistically significant changes in efficacy parameters. The reasons for this disparity are not known.ConclusionsCligosiban was well tolerated but failed to demonstrate efficacy for the treatment of men with lifelong PE at doses up to 1200 mg.Althof S, Osterloh IH, Muirhead GJ, et al. The Oxytocin Antagonist Cligosiban Fails to Prolong Intravaginal Ejaculatory Latency in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Phase IIb trial (PEDRIX). J Sex Med 2019; 16:1188–1198.     

Efficacy and Safety of Dapoxetine in Men with Premature Ejaculation and Concomitant Erectile Dysfunction Treated with a Phosphodiesterase Type 5 Inhibitor: Randomized,Placebo-Controlled,Phase III Study

IntroductionMen with comorbid erectile dysfunction (ED) and premature ejaculation (PE) may be concomitantly prescribed a phosphodiesterase type 5 (PDE5) inhibitor and dapoxetine.AimEvaluate efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE and ED who were being treated with PDE5 inhibitors.MethodsThis randomized, double-blind, placebo-controlled, flexible-dose, multicenter study enrolled men ≥18 years who met diagnostic criteria for PE including intravaginal ejaculatory latency time (IELT) of ≤2 minutes in ≥75% of sexual intercourse episodes; were on stable regimen of a PDE5 inhibitor; and had International Index of Erectile Function-erectile function domain score ≥21. Subjects received placebo, dapoxetine 30 mg, or dapoxetine 60 mg prn (1–3 hours before intercourse) for 12 weeks.Main Outcome MeasureStopwatch-measured average IELT, Clinical Global Impression of Change (CGIC) in PE, Premature Ejaculation Profile (PEP), and treatment-emergent adverse events (TEAEs).ResultsOf 495 subjects randomized, 429 completed the study. Arithmetic mean average IELT significantly increased with dapoxetine vs. placebo at end point (5.2 vs. 3.4 minutes) and weeks 4, 8, and 12 (P ≤ 0.002 for all). Men who described their PE at least “better” using the CGIC were significantly greater with dapoxetine vs. placebo at end point (56.5% vs. 35.4%) and weeks 4, 8, and 12 (P ≤ 0.001 for all). Significantly better outcomes were also reported with dapoxetine vs. placebo on PEP measures. Incidence of TEAEs was 20.0% and 29.6% in placebo- and dapoxetine-treated subjects, respectively (P = 0.0135). TEAEs led to discontinuation in 1.6% of subjects in both groups. Most frequent TEAEs were known adverse drug reactions of dapoxetine treatment including nausea (9.2%), headache (4.4%), diarrhea (3.6%), dizziness (2.4%), and dizziness postural (2.4%).ConclusionsIn men with PE and comorbid ED on a stable regimen of PDE5 inhibitor, dapoxetine provided meaningful treatment benefit and was generally well tolerated. McMahon CG, Giuliano F, Dean J, Hellstrom WJG, Bull S, Tesfaye F, Sharma O, Rivas DA, and Aquilina JW. Efficacy and safety of dapoxetine in men with premature ejaculation and concomitant erectile dysfunction treated with a phosphodiesterase type 5 inhibitor: Randomized, placebo-controlled, phase III study. J Sex Med 2013;10:2312–2325.     

Clinical Correlates of Erectile Dysfunction and Premature Ejaculation in Men with Couple Infertility

IntroductionThe frequency and the clinical characteristics of erectile dysfunction (ED) and premature ejaculation (PE) in infertile men have been poorly investigated.AimTo assess the prevalence of ED and PE and their clinical correlates in men seeking medical care for couple infertility.MethodsA consecutive series of 244 men (mean age 35.2 ± 7.8) with couple infertility was systematically evaluated. Erectile function was investigated with the International Index of Erectile Function‐15 erectile function domain (IIEF‐15‐EFD) whereas ejaculatory status with the PE diagnostic tool (PEDT).Main Outcome MeasuresAll patients underwent psychological (Middlesex Hospital Questionnaire [MHQ]), prostatitis symptoms (National Institutes of Health–chronic prostatitis symptom index [NIH‐CPSI]); hormonal, seminal, and interleukin 8 (sIL‐8; a surrogate marker of prostatitis) evaluation; along with scrotal and transrectal color Doppler ultrasound (CDU) assessment.ResultsED was found in 43 (17.8%) and PE in 38 (15.6%) subjects. After adjusting for age, IIEF‐15‐EFD score was negatively associated with depressive symptoms (MHQ‐D score), somatization (MHQ‐S score), NIH‐CPSI total, and quality of life subdomain score. In a logistic multivariate model, among all these variables, only depression was significantly associated with ED (adjusted odds ratio [OR] = 1.19 [1.02–1.39]; P < 0.05). PEDT score was positively associated with prostatitis symptoms and signs, such as sIL‐8 and prostate CDU abnormalities (including arterial prostatic peak systolic velocity, APPSV), phobic anxiety (MHQ‐P score), and calculated free testosterone (cFT). The association between PE and NIH‐CPSI score or APPSV was confirmed even after adjustment for age, MHQ‐P score and cFT (adjusted OR = 1.11 [1.05–1.17]; P < 0.0001 and 1.22 [1.03–1.44]; P = 0.02, for NIH‐CPSI score and APPSV, respectively).ConclusionsED and PE are reported by one in six infertile patients. ED is mainly associated with depressive symptoms, while PEDT score is positively associated with prostatitis symptoms and signs, phobic anxiety, and cFT. Lotti F, Corona G, Rastrelli G, Forti G, Jannini EA, and Maggi M. Clinical correlates of erectile dysfunction and premature ejaculation in men with couple infertility. J Sex Med **;**:**–**.     

Canadian Male Sexual Health Council Survey to Assess Prevalence and Treatment of Premature Ejaculation in Canada

IntroductionThis study evaluated the prevalence of complaints of premature ejaculation (PE) among a cross-sectional sample of Canadian males and their partners.AimIt sought to quantify measures of behavior and attitudes as they relate to PE. It evaluated the level of patient knowledge, physician engagement, and patient satisfaction with treatment options for PE, a common sexual complaint. It also explored the patient and partner-reported impacts on quality of life and well-being.Main Outcome MeasureThe main outcome measure for the study was the statistical analysis of data on different facets of PE and associated factors from a comprehensive population-based survey conducted in Canada.MethodsA web-based survey was carried out among adults in Canada (phase 1, N = 3,816) followed by a focused telephone interview in phase 2 for those who met the criteria for PE (phase 2, N = 1,636). Men were classified as having PE based on self-report of low or absent control over ejaculation, irrespective of the duration of the ejaculation time, resulting in distress for them or their sexual partner or both, or reporting that they “climaxed too soon.”ResultsThe prevalence of PE in the survey, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders-III criteria, ranged from 16% to 24% depending on the definition of PE utilized, and did not vary significantly with age. Ninety percent of those with a determination of PE in this survey had not discussed alternatives to prolong time to ejaculation with a physician, pointing to gaps in patient/physician communication around sexual health.ConclusionsPE is a prevalent sexual problem that poses special challenges to clinicians and causes considerable burden to Canadian men and their partners. There remains a stigma associated with PE, resulting in the existence of significant barriers to obtaining assistance from physicians for this problem. The majority of those interviewed who sought and received treatment have not been satisfied with the results. Brock GB, Bénard F, Casey R, Elliott SL, Gajewski JB, and Lee JC. Prevalence and treatment of premature ejaculation in Canada. J Sex Med 2009;6:2115–2123.     

Validity of the Patient-Reported Clinical Global Impression of Change as a Measure of Treatment Response in Men with Premature Ejaculation

IntroductionThe Clinical Global Impression of Change (CGIC) measures have high utility in clinical practice. However, it is unknown whether the CGIC is valued for assessing premature ejaculation (PE) symptoms and/or the relationship between CGIC and other validated PE patient-reported measures.AimThe study aims to assess the validity of the patient-reported CGIC measure in men with PE and to examine the relationship between CGIC ratings and assessments of control, satisfaction, personal distress, and interpersonal difficulty.MethodsData from a randomized, double-blind, 24-week phase 3 trial in 1,162 men with PE who received dapoxetine (30 mg or 60 mg) or placebo on demand provided the basis for the analysis. Patients were ≥18 years, in a stable monogamous relationship for ≥6 months, met the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision criteria for PE for ≥6 months, and had an intravaginal ejaculatory latency time (IELT) ≤2 minutes in ≥75% of intercourse episodes.Main Outcome MeasuresThe CGIC asked patients to rate improvement or worsening of their PE compared with the start of the study using a 7-point response scale; other patient-reported measures were control over ejaculation, satisfaction with sexual intercourse, interpersonal difficulty, and personal distress related to ejaculation. Stopwatch-measured IELT was recorded. Associations between CGIC and change in other measures at study end point were assessed.ResultsThe magnitude of IELT increased for each category of improvement on the CGIC: 1.63, 4.03, and 7.15 minutes for slightly better, better, and much better, respectively. Higher CGIC ratings were correlated with greater improvement in control (r = 0.73), satisfaction (r = 0.62), greater reduction in distress (r = ?0.52), and interpersonal difficulty (r = ?0.39). Total variance accounted for was 57.4%: control (48.7%), satisfaction (4.5%), IELT (2.8%), and distress (1.15%).ConclusionsThe analyses support the validity of the CGIC measure in men with PE. The CGIC can provide clinicians in practice with a valid and brief outcome assessment of their patient's condition. Althof SE, Brock GB, Rosen RC, Rowland DL, Aquilina JW, Rothman M, Tesfaye F, and Bull S. Validity of the patient-reported clinical global impression of change as a measure of treatment response in men with premature ejaculation.