Variations in objectively measured sleep parameters in patients with different premature ejaculation syndromes.

BACKGROUND: Poor sleep quality is now a cause of sexual dysfunction. AIM: To investigate variations in sleep quality among patients with different types of premature ejaculation (PE) and a control group. METHODS: Patients with PE were categorized into groups according to 4 types: lifelong (LPE), acquired (APE), variable (VPE), and subjective (SPE). Basic demographic information about the participants was first collected, and then clinical data were obtained. OUTCOMES: Outcomes included the 5-item International Index of Erectile Function, Premature Ejaculation Diagnostic Tool, 7-item Generalized Anxiety Disorder, 9-item Patient Health Questionnaire, Pittsburgh Sleep Quality Index, self-estimated intravaginal ejaculation latency time (minutes), and sleep monitoring parameters obtained from a wearable device (Fitbit Charge 2). RESULTS: A total of 215 participants were enrolled in the study, of which 136 patients with PE were distributed as follows: LPE (31.62%), APE (42.65%), VPE (10.29%), and SPE (15.44%). Subjective scales showed that patients with APE were accompanied by a higher prevalence of erectile dysfunction, anxiety, and depression, as well as poorer sleep quality (assessed by the Pittsburgh Sleep Quality Index). The results of objective sleep parameters revealed that average durations of sleep onset latency (minutes) and wake after sleep onset (minutes) in patients with APE (mean ± SD; 20.03 ± 9.14, 55 ± 23.15) were significantly higher than those with LPE (15.07 ± 5.19, 45.09 ± 20.14), VPE (13.64 ± 3.73, 38.14 ± 11.53), and SPE (14.81 ± 4.33, 42.86 ± 13.14) and the control group (12.48 ± 3.45, 37.14 ± 15.01; P < .05). The average duration of rapid eye movement (REM; minutes) in patients with APE (71.34 ± 23.18) was significantly lower than that in patients with LPE (79.67 ± 21.53), VPE (85.93 ± 6.93), and SPE (80.86 ± 13.04) and the control group (86.56 ± 11.93; P < .05). Similarly, when compared with the control group, patients with LPE had significantly longer durations of sleep onset latency and wake after sleep onset and a significantly shorter duration of REM sleep. CLINICAL IMPLICATIONS: Our study suggests that clinicians should pay attention not only to male physical assessment but also to mental health and sleep quality. STRENGTHS AND LIMITATIONS: This study suggests that changes in sleep structure occur in patients with PE, which may provide some direction for future research. However, the cross-sectional study design does not allow us to conclude that sleep is a risk factor for PE. CONCLUSION: After controlling for traditional parameters such as age, erectile dysfunction, anxiety, and depression, sleep parameters are independently associated with PE. Patients with APE and LPE show significant alterations in sleep parameters, with patients with APE having notably poorer sleep quality, whereas patients with VPE and SPE have sleep parameters similar to controls.

Glans penis volume is associated with lifelong premature ejaculation.

BACKGROUND: Although premature ejaculation (PE) is the most common male sexual dysfunction, the underlying mechanisms are not fully understood. AIM: The study sought to evaluate the possible associations among glans penis volume and tissue stiffness measured using penile ultrasonography and penile shear wave elastography (SWE) with PE. METHODS: Men 18 to 65 years of age with normal International Index of Erectile Function scores (>25) and who were diagnosed with PE between June 2021 and June 2022 were enrolled. The Premature Ejaculation Diagnostic Tool score and intravaginal ejaculation latency times were recorded. Healthy volunteers constituted the control group. The study group was divided into lifelong PE (LLPE) and acquired PE (AqPE) subgroups. In all groups, the glans penis volume was measured via penile ultrasonography and tissue stiffness of the glans penis, penile frenulum, postcircumcision mucosal cuff, and penile shaft were measured via SWE. The findings of the groups were compared using appropriate statistical methods. OUTCOMES: The outcomes included ultrasonographic and elastographic measurements of the glans penis. RESULTS: Data on 140 men, including 70 PE patients and 70 healthy volunteers, were evaluated. Of the patients, 20 had LLPE and 50 had AqPE. The median glans penis volume was significantly greater in the LLPE group (14.1 [range, 6.6-19] mm3) compared with the AqPE group (11.7 [range, 5.1-27] mm3) and control group (11.4 [range, 6.1-32] mm3) (P = .03). According to the Youden index, the best cutoff value for glans penis volume in LLPE compared with non-LLPE (AqPE + control) was 12.65 mm3 (area under the curve, 0.684; 95% confidence interval, 0.556-0.812; P = .009). The risk of having LLPE in those with a glans penis volume ≥12.65 mm3 was 3.326 (95% confidence interval, 1.234-8.965) times higher than the non-LLPE group (P = .014). There were no significant differences between the groups in the SWE evaluation of glans penis, penile frenulum, mucosal cuff, and penile shaft tissue stiffness. CLINICAL IMPLICATIONS: The high incidence of PE in those with high glans penis volume may make glans penis volume a predictor for the development of LLPE. STRENGTHS AND LIMITATIONS: This was the first study to show that PE is more common in individuals with a high glans penis volume. It was also the first to perform a penile elastographic evaluation in patients with PE. The most important limitation was that we did not evaluate glans penile nerve function with a test, but rather we made an indirect inference about the density of free nerve endings based on increased glans penile volume. CONCLUSION: Glans penis volume was a significant predictor for LLPE. However, there are no associations between PE and the glans penis, postcircumcision mucosal cuff, penile frenulum, or penile shaft tissue stiffness and development.

The Diagnostic Role of Neurophysiological Tests for Premature Ejaculation: A Prospective Multicenter Study.

PURPOSE: Premature ejaculation (PE) is one of the most common male sexual dysfunctions. Local anesthetics (LAs) and dapoxetine are frequently used to treat PE; however, previous studies show variable efficacy. This study aims to determine the efficacy of LAs and dapoxetine using a novel classification based on neurophysiological tests. MATERIALS AND METHODS: This multicenter cohort study enrolled adult men (568) with an intravaginal ejaculatory latency time (IELT) ≤2 minutes. Patients were divided into 4 groups according to the results of neurophysiological tests and assigned different treatments for 12 weeks: 1) penile sensory hyperexcitability type (Sens)-LAs; 2) penile sympathetic hyperexcitability type (Symp)-dapoxetine; 3) mixed type (Mixed)-both LAs and dapoxetine; 4) normal type (Norm)-both LAs and dapoxetine. Self-estimated IELT and patient-reported outcomes were recorded. RESULTS: The total percentage of men achieving IELT >2 minutes and ≥5 minutes after treatment were 82.7% and 76.7%, respectively. For men with abnormal results of neurophysiological tests, 401 (86.6%) had improved IELT >2 minutes after the 12-week treatment course, in which 375 (81.0%) achieved IELT ≥5 minutes. All patient-reported outcome measures improved in each group after 12 weeks of treatment, with greater improvements among those with abnormal neurophysiological tests. CONCLUSIONS: The efficacy of LAs and dapoxetine increased in PE patients with abnormal results of neurophysiological tests. This novel classification of PE using neurophysiological tests could help guide and improve efficacy of PE therapies.

Management of premature ejaculation: a clinical guideline from the Italian Society of Andrology and Sexual Medicine (SIAMS).

Premature ejaculation (PE) is the most prevalent male sexual dysfunction, and the most recently defined. PE is often mistakenly considered a purely psychosexological symptom by patients: the lacking awareness in regards to the pathophysiology and treatments often lead to resignation from the patients' side, making PE the most underdiagnosed sexual complaint. However, an ever-growing body of evidence supporting several organic factors has been developed in the last decades and several definitions have been suggested to encompass all defining features of PE. In the present document by the Italian Society of Andrology and Sexual Medicine (SIAMS), we propose 33 recommendations concerning the definition, pathophysiology, treatment and management of PE aimed to improve patient care. These evidence-based clinical guidelines provide the necessary up-to-date guidance in the context of PE secondary to organic and psychosexological conditions, such as prostate inflammation, endocrine disorders, and other sexual dysfunctions, and suggest how to associate pharmacotherapies and cognitive-behavioral therapy in a couple-centered approach. New therapeutic options, as well as combination and off-label treatments, are also described.

Variation in Brain Subcortical Network Topology Between Men With and Without PE: A Diffusion Tensor Imaging Study.

INTRODUCTION: Premature ejaculation (PE) is a highly prevalent male sexual dysfunction. Previous studies have found abnormal activity in the sympathetic nervous system and penile sensory pathway of PE. Few studies have investigated the neural mechanisms underlying PE. AIM: The aim of this study was to examine whether the altered cortico-subcortical network topological properties of the brain white matter structural network could be used to differentiate patients with PE from healthy control (HC) subjects. METHODS: Diffusion tensor images data were collected from 32 patients with PE and 35 HC participants. Then, brain white matter structural networks were reconstructed from image acquisition. MAIN OUTCOME MEASURE: Furthermore, nodal measures were calculated and hub regions were identified using the graph-theoretical methods. RESULTS: For cortical brain regions, increased strength, global efficiency, and decreased shortest path length were found in the right superior frontal gyrus (medial), and superior frontal gyrus (medial orbital) were found in patients with PE. In addition, patients with PE also showed decreased strength in the right rolandic operculum and decreased shortest path length, and increased global efficiency in the right inferior frontal gyrus (triangular part). For subcortical brain structures, patients with PE were associated with decreased shortest path length and increased global efficiency in the left insula and right caudate nucleus. Finally, the results showed that 9 PE-specific hub regions were identified in patients compared with HCs, including 7 cortical regions and 2 subcortical regions. CLINICAL IMPLICATIONS: Our results provide new understanding about the pathology of PE and enhances the understanding of PE pathology. STRENGTH & LIMITATIONS: Our results offer biological markers for understanding the physiopathology of PE. However, our study is a cross-sectional design, longitudinal design studies need to explore the causal relationships between aberrant topological characteristics and PE. CONCLUSION: Our results provide new insights into the neural mechanism of PE involving cortico-subcortical network changes, which could serve as a potential biomarker to differentiate individuals with PE from HCs. Chen J, Yang J, Huang X, et al. Variation in Brain Subcortical Network Topology Between Men With and Without PE: A Diffusion Tensor Imaging Study. J Sex Med 2020;17:48-59.

A Double Blind, Placebo Controlled, Randomized Trial to Evaluate the Efficacy and Tolerability of On-Demand Oral Pregablin (150 mg and 75 mg) in Treatment of Premature Ejaculation.

INTRODUCTION: Although premature ejaculation (PE) is a common sexual dysfunction, the available options for PE treatment remain unsatisfactory. AIM: To evaluate the effect of on-demand oral pregabalin on the intravaginal ejaculation latency time (IELT). METHOD: We conducted a multiarm double-blinded placebo-controlled randomized clinical trial that enrolled 120 patients with PE who were divided equally into 3 groups (A, B, and C). 4 patients were excluded, 39 patients received 150 mg pregabalin (group A), 39 patients received 75 mg pregabalin (group B), and 38 patients received placebo (group C). All patients were encouraged to engage in sexual relations twice per week for 2 weeks and to take the medication 1-2 hours before sexual intercourse. A stopwatch was used to evaluate IELT. MAIN OUTCOME MEASURE: The main outcome measure are the improvement of IELT and the reported adverse events. RESULTS: IELT significantly improved in patients who received 150 mg pregabalin, but there was no change in the other groups. CLINICAL IMPLICATIONS: Most PE patients showed a significant improvement after receiving on-demand pregabalin (150 mg). STRENGTH & LIMITATIONS: The strength of this study is that it is the first randomized controlled trial to evaluate the efficacy of pregabalin in treatment of PE. The main limitations were the small number of patients, IELT was the only primary outcome of the study, and the pregabalin cap can be identified by the patient. CONCLUSION: Oral pregabalin seems to be a promising drug for additional evaluation as a new treatment for PE. More studies are needed to evaluate the suitable dose, duration, timing, and its safety profile. El Najjar MR, El Hariri M, Ramadan A, et al. A Double Blind, Placebo Controlled, Randomized Trial to Evaluate the Efficacy and Tolerability of On-Demand Oral Pregablin (150 mg and 75 mg) in Treatment of Premature Ejaculation. J Sex Med 2020;17:442-446.

The efficacy of regular penis-root masturbation, versus Kegel exercise in the treatment of primary premature ejaculation: A quasi-randomised controlled trial.

To explore the efficacy of regular penis-root masturbation (PRM) versus Kegel exercise (KE) in the treatment of primary premature ejaculation (PPE). This study was a prospective quasi-randomised controlled trial. Thirty-seven heterosexual males with PPE were selected according to the time sequence of outpatient consultations and the preliminary results of a pre-experiment and were assigned to an PRM group and a KE group. Differences in intravaginal ejaculatory latency times (IELTs) and premature ejaculation diagnostic tool (PEDT) scores were compared between the two groups. The study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University. Among the 37 PPE patients, 18 performed PRM and 19 patients performed KE. The IELTs of patients who performed PRM and KE were significantly prolonged before treatment, and the difference after treatment was statistically significant (p < .05). Compared with the KE group, the IELT prolongation effect in the PRM group was more significant PRM (p < .05). The PEDT scores of patients after performing PRM and KE were significantly lower than those before performing these exercises (p < .05). Compared with the KE group, the PEDT scores of the PRM group exhibited a greater decrease (p < .05). Thus, both PRM and KE have therapeutic effects on PPE. Compared with KE, PRM is more effective in the treatment of PPE.

The heart rate recovery is impaired in participants with premature ejaculation.

Premature ejaculation (PE) is one of the most common sexual disorders in men. Excessive activity of the sympathetic nervous system is considered as one of the pathological mechanisms of PE. Heart rate recovery (HRR) is a noninvasive and easily applicable method for evaluating autonomic functions. We aimed to investigate the relationship between PE and HRR. This cross-sectional study included 42 consecutive patients with lifelong PE and 98 healthy volunteers. All participants underwent stress tests according to age-dependent target heart rates outlined in the Bruce protocol. When the maximal heart rate was reached in the stress test, intensive exercise was terminated and electrocardiographic records were obtained for 3 min in the cool-down period. The HRR indices were calculated by subtracting the heart rate at first, second and third minutes from the maximal HR. The two groups were similar in terms of age, body mass index, serum glucose and lipid parameters. HRR indices were significantly lower in the PE group compared with the control group (p < .05 for all). Common factors that affect equilibrium of sympathetic and parasympathetic nervous systems may be involved in the PE and abnormal HRR etiopathogenesis. The cause-and-effect relationship can be more clearly demonstrated with large-scale, prospective studies.

The Penile Sensitivity Ratio: A Novel Application of Biothesiometry to Assess Changes in Penile Sensitivity.

INTRODUCTION: Biothesiometry allows for evaluation of penile vibratory sensitivity and can be used as a non-invasive and rapid surrogate test of penile sexual sensitivity. However, no standardized measurement methodology currently exists. AIM: To describe and optimize a novel, standardized biothesiometry parameter-the penile sensitivity ratio (PSR). METHODS: We reviewed all biothesiometry data from men presenting to our institution from July 2013-May 2017. 3 iterations of the PSR were evaluated using the threshold for vibratory detection from a combination of different input variables including the penile glans, penile shaft, index finger, and thigh. Numerator values for the PSR included the penile glans and penile shaft, whereas denominator inputs included the index finger and thigh. PSR is inversely correlated with penile sensitivity. MAIN OUTCOME MEASURE: The primary outcome measure was the association between reported diminished penile sensitivity and PSR value. Secondary outcome measures were the association between PSR and age, diabetes, ejaculatory dysfunction, and Peyronie's disease (PD). RESULTS: Biothesiometry data were evaluated from 1,239 men. Mean age was 53.2 years (SD 14.0 years). Diabetes was present in 7.4% (n = 92); 52.0% (n = 644) had PD. Ejaculatory dysfunction was identified in 15.8% (n = 196), with 12.2% (n = 151) having premature ejaculation and 3.6% (n = 45) reporting delayed ejaculation. Decreased penile sensitivity was reported in 20.3% (n = 252). 3 PSR iterations were analyzed to identify associations with decreased penile sensation. On univariate and multivariate analysis controlling for age, diabetes, ejaculatory dysfunction, and PD, only the PSR iteration, which included data from the penile glans and finger (PSRG/F), was significantly different between patients reporting diminished penile sensitivity and those without reported diminished sensitivity (univariate P < .01, multivariate P = .03). On univariate analysis, a higher PSRG/F was associated with older age (P < .01) and diabetes (P < .01), whereas men with PD had a lower PSRG/F (P < .01). On multivariate analysis, PSRG/F remained increased for age (P < .01) and decreased for PD (P = .01); however, there was no association with diabetes (P = .12). No association existed between ejaculatory function and PSRG/F on univariate (P = .25) or multivariate analysis (P = .35). CLINICAL IMPLICATIONS: The PSR may be used as a standardized biothesiometry parameter to evaluate penile sensitivity. STRENGTH & LIMITATIONS: This study included a large cohort of men undergoing biothesiometry (n = 1,239); however, it is limited by the multifactorial nature of perceived diminished penile sensitivity. CONCLUSION: The PSR using penile glans and index finger input variables is a non-invasive, painless, office-based, standardized biothesiometry parameter that is a clinically useful tool for measuring penile sexual sensitivity. Wiggins A, Farrell MR, Tsambarlis P, et al. The Penile Sensitivity Ratio: A Novel Application of Biothesiometry to Assess Changes in Penile Sensitivity. J Sex Med 2019;16:447-451.

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. AIM: To explore the content validity of the PEP (original 1-month recall version and new event-driven version) in men meeting current definitions of lifelong PE and to understand the relevance of the concept of ejaculation control. METHODS: In-depth individual interviews were conducted with 24 men in a stable heterosexual relationship, including 15 with lifelong PE, 4 with acquired PE (with intravaginal ejaculation latency time values confirmed during a 4-week period of no treatment), and 5 with no sexual dysfunction. Initial concept elicitation explored individual experiences of having PE (in those with PE), experiences of control, and impact on sexual life. This was followed by a cognitive debriefing of the PEP versions. MAIN OUTCOME MEASURE: Thematic analysis was used to identify key concepts of PE, understand the experience of control in men with and without PE, and confirm understanding and relevance of questions from original and event-driven versions of the PEP. RESULTS: The interviews confirmed substantial negative consequences for men with lifelong PE. Men with and without PE could describe ejaculation control (or lack of it). The PEP was shown to cover the key concepts in PE, and the questions were easily understood in both the original or event-driven versions. The items were comprehensive, and the concept of ejaculation control was confirmed. A 1- or 2-category change in each item of the PEP was considered clinically meaningful. CLINICAL IMPLICATIONS: The PEP (original and per-event) has strong content validity for use in clinical research studies of men meeting the ISSM definition of lifelong PE. STRENGTHS & LIMITATIONS: This study addressed gaps in previously published research on the development and validation of the PEP and also confirmed that a new event-driven version is also suitable for use in research. However, the study was limited mainly to men meeting a strict definition of lifelong PE; in addition, homosexual men and those not in stable long-term relationships were not studied. CONCLUSION: Both the original and per-event PEP versions were shown to have strong content validity and be acceptable for use in men with lifelong PE. Burbridge C, Symonds T, Osterloh IH, et al. Content Validity of the Premature Ejaculation Profile, Original and Per-Event Formats, in Men with Lifelong Premature Ejaculation. J Sex Med 2019;16:569-576.

Erectile Dysfunction and Premature Ejaculation in Homosexual and Heterosexual Men: A Systematic Review and Meta-Analysis of Comparative Studies.

INTRODUCTION: Comparative studies on differences in sexual function outcomes between homosexual and heterosexual men are sparse and inconclusive. AIM: To systematically evaluate whether, and to what extent, a statistically significant difference exists in the odds of erectile dysfunction (ED) and premature ejaculation (PE) between homosexual and heterosexual men. METHODS: A thorough search of Medline, SCOPUS, CINAHL, and Web of Science databases was carried out to identify case-control studies comparing the prevalence of ED and PE in homosexual and heterosexual men. Methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Odds ratios (ORs) of reporting ED and PE were combined using random effect models. The Cochrane Q and I2 tests were carried out to analyze the between-studies heterogeneity. Funnel plots and trim-and-fill analysis were used to assess publication bias. MAIN OUTCOME MEASURES: The relationship between sexual orientation and odds of ED and PE was assessed by calculating pooled ORs with a 95% CI. RESULTS: 4 studies included in the quantitative analysis collectively provided information on 1,807 homosexual and 4,055 heterosexual men. The pooled ORs indicated that homosexual orientation was associated with 1.5-fold higher odds of reporting ED (OR = 1.49, 95% CI = 1.03-2.16; P = .04) and 28.0% lower odds of reporting PE in comparison to the heterosexual orientation (OR = 0.72, 95% CI = 0.52-1.00; P = .05). However, a significant heterogeneity among the studies was observed. Funnel plots revealed a possible publication bias only for the ED analysis, where the trim-and-fill test detected a putative missing study. Nevertheless, even when the pooled estimate was adjusted for publication bias, there was a significantly higher risk of ED in the homosexual group (adjusted OR = 1.60, 95% CI = 1.10-2.30; P = .01). CLINICAL IMPLICATIONS: These findings can drive future studies on sexual needs and concerns of homosexual men, which might not exactly match those of heterosexual individuals. STRENGTH & LIMITATIONS: This is the first meta-analysis exploring the differences in the prevalence of ED and PE between homosexual and heterosexual men. However, the results should be interpreted with caution, because their generalization could be hindered by the non-probabilistic nature of the samples, and a measurement bias could result from the use of different non-standardized indicators of sexual dysfunctions. CONCLUSION: Homosexual orientation is associated with higher odds of ED and lower odds of PE compared with heterosexual orientation. Further studies are warranted to elucidate the clinical significance of these findings and whether they reflect differences in patterns of sexual lifestyle. Barbonetti A, D'Andrea S, Cavallo F, et al. Erectile Dysfunction and Premature Ejaculation in Homosexual and Heterosexual Men: A Systematic Review and Meta-Analysis of Comparative Studies. J Sex Med 2019;16:624-632.

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. AIM: To evaluate anatomic basis and clinical effect of SDN in patients with PE in mainland China. METHODS: All of the patients included in the study had redundant foreskin, and they were assigned to 2 groups: group 1, composed of 46 patients with redundant foreskin, and group 2, composed of 96 patients with redundant foreskin and PE. The patients in group 2 were further randomly classified into group 2a (n = 48) and group 2b (n = 48). MAIN OUTCOME MEASURES: The number of dorsal penile nerve branches were compared among group 1, group 2a, and group 2b. Preoperative and postoperative intravaginal ejaculatory latency time (IELT), 5-item version of the International Index of Erectile Function, Premature Ejaculation Diagnostic Tool, and postoperative complications were compared between group 2a and group 2b. RESULTS: The patients in group 2 had a greater number of dorsal penile nerve branches of 1-2-mm-diameter, ≥2-mm-diameter, and total branches than group 1. The postoperative IELT of group 2a (257.7 ± 205.7 seconds) was longer than that of group 2b (49.3 ± 26.1 seconds). Group 2a had more ejaculation controllability and lower Premature Ejaculation Diagnostic Tool scores than group 2b after the surgery (P < .001). We did not observe permanent numbness in glans, wound infection, or hematoma in any patients. CLINICAL IMPLICATION: SDN is an effective treatment for lifelong PE patients who had poor response to medicine or refused oral medication. STRENGTH & LIMITATIONS: This study has some strengths. First, the study made a comprehensive comparison based on both the numbers of dorsal penile nerve branches and the effect. Second, a randomized controlled trial design was used for the evaluation of SDN. It also possesses a limitation-we did not determine how many dorsal nerves should be selectively resected for each person to achieve optimal IELT prolongation. CONCLUSION: The dorsal penile nerve branches of patients with lifelong PE are more and thicker than those without lifelong PE, and SDN is effective in improving lifelong PE by IELT prolongation and ejaculation controllability, with few postoperative complications. Liu Q, Li S, Zhang Y, et al. Anatomic Basis and Clinical Effect of Selective Dorsal Neurectomy for Patients with Lifelong Premature Ejaculation: A Randomized Controlled Trial. J Sex Med 2019;16:522-530.

Ten-Year Interval Changes in the Prevalence of Self-Identified Premature Ejaculation and Premature Ejaculation Based on an Estimated Intravaginal Ejaculation Latency Time of <3 Minutes in the General Population: The Korean Internet Sexuality Survey (KISS) 2016.

INTRODUCTION: Because the prevalence of premature ejaculation (PE) may change with time, few studies have been conducted over a 10-year time interval. AIM: A 10-year time interval survey to determine whether there was a change in the prevalence of self-identified PE and PE defined on the basis of an estimated intravaginal ejaculation latency time of <3 minutes in adult Korean men, even after adjusting for various sociocultural factors. METHODS: We sent an e-mail to the panels registered in the same Internet survey agency in 2006, asking them to participate in a questionnaire-based survey of the same study design. 1,401 participants were enrolled in the 2016 study that included 800 subjects in their 20s-50s. The PE prevalence adjusted for age was evaluated because the proportion of participants per age was different between the 2 surveys. The age-adjusted prevalence of self-identified PE and PE with an estimated intravaginal ejaculation latency time of 3 minutes, which meets the diagnostic criteria for PE set by the International Society for Sexual Medicine (PE), was evaluated. MAIN OUTCOME MEASURES: Changes in the overall prevalence of self-identified PE and PE in over a decade were evaluated. RESULTS: The overall age-adjusted prevalence of self-identified PE increased from 19.0% in 2006 to 21.6% in 2016; however, the result was not statistically significant (P = .244). The overall age-adjusted prevalence of PE increased from 1.8-4.0% in 2006 and 2016, respectively (P = .012). The risk factors of self-identified PE were few intercourses per month, masturbation, and self-identified erectile dysfunction. In addition, the risk factors of PE were aging, high body mass index, few intercourses per month, and masturbation. CLINICAL IMPLICATION: The prevalence of PE has increased over 10 years. However, this increase may be due to sociocultural changes and should be more concerned with these factors. STRENGTH & LIMITATIONS: This study was the first to conduct a 10-year interval Web-based survey on the prevalence and risk factors of PE. However, this was not a cohort study with the same participants. CONCLUSION: The overall age-adjusted prevalence of PE increased significantly over a decade, and sociocultural factors such as lifestyle were associated with the difference of PE prevalence for 10 years. However, more research is needed to determine how these sociocultural changes affect PE prevalence. Song WH, Yoo S, Oh S, et al. Ten-Year Interval Changes in the Prevalence of Self-Identified Premature Ejaculation and Premature Ejaculation Based on an Estimated Intravaginal Ejaculation Latency Time of <3 Minutes in the General Population: The Korean Internet Sexuality Survey (KISS) 2016. J Sex Med 2019;16:512-521.

Association Between Post-Ejaculatory Refractory Time (PERT) and Premature Ejaculation (PE).

INTRODUCTION: Patients with premature ejaculation (PE) often complain of difficulty in having second erection, which is not yet investigated using scientific methodology. AIM: Evaluation of the association between post-ejaculation refractory time (PERT) with PE by comparing PERT in premature ejaculators with their age-matched control subjects. METHODS: After ethical committee approval and written informed consent from the participants were obtained, men in a monogamous stable sexual relationship and reporting PE were recruited into the study. Sexually active, matched control subjects were recruited for comparison. Exclusion criteria were erectile dysfunction, diabetes mellitus, cardiovascular diseases, hypogonadism, psychiatric conditions, instrumentation of the genitourinary tract, genitourinary anomalies, and genitourinary infections. Both the premature ejaculators and their control subjects were evaluated with the PE diagnostic tool before initiation of the study. They were asked to record their IELT and PERT over 4 weeks. The statistical analysis was done to obtain descriptive statistics, namely, mean and SD, paired t-tests, and logistic regression analysis. P < .001 was considered significant. MAIN OUTCOME MEASURE: There was a statistically significant association between prolonged PERT and PE in patients with PE compared with their age-matched control subjects. RESULTS: 102 premature ejaculators and an equal number of matched control subjects were evaluated from January 2016-December 2017. The average PERT in premature ejaculators and control subjects was 330 ± 296.63 minutes and 105.64 ± 98.59 minutes, respectively (P < .0001). Increasing age was associated with increasing PERT. PE was more common in patients when PERT exceeded a threshold of 590 minutes. CLINICAL IMPLICATIONS: Until now, the association between PE and PERT with matched-pair analysis was not reported. Our study addresses this association, which can add a new paradigm in the evaluation and management of PE. STRENGTH & LIMITATIONS: The association between PE and prolonged PERT using a statistically appropriate, adequately powered methodology is the strength of the study. The inability to address the causal association between prolonged PERT and PE because of the paucity of evidence at present is the limitation of the study. We believe that the results of this study could trigger further research into such an association, so the mystery of such an association can be unraveled. CONCLUSIONS: The association between prolonged PERT and PE, as seen in our study, is a finding, that needs further research to establish a causal association. However, reporting such an association is necessary because it is contrary to the present understanding. Bhat GS, Shastry A. Association Between Post-Ejaculatory Refractory Time (PERT) and Premature Ejaculation (PE). J Sex Med 2019;16:1364-1370.

Can Botulinum-A Toxin Be Used to Delay Ejaculation: Results of an Ejaculation Model in Male Rats.

INTRODUCTION: Although premature ejaculation (PE) is the most common sexual dysfunction in young men, its true pathophysiology has not yet been clearly elucidated. AIM: To investigate the quantitative changes that occurred in an ejaculation model induced by para-chloroamphetamine (PCA) after botulinum-A toxin injection into the bulbospongiosus (BS) muscle in rats. METHODS: A total of 21 male rats weighing 300 to 350 grams were used in the study. The animals were divided into 3 groups: control, 1 unit of botulinum-A toxin injected, and 5 units of botulinum-A toxin injected. The botulinum-A toxin was percutaneously injected into the BS muscle, and the experiment was carried out 96 hours (5 days) after the injection. MAIN OUTCOME MEASURE: The seminal vesicle (SV) was cannulated, and the BS muscle was dissected and connected to an amplifier (Biopac; Goleta, CA) to record the pressure and electromyography measurement. The ejaculation parameters were obtained after the PCA injection. RESULTS: The ejaculation latency time of the group receiving 5 units of botulinum-A toxin was statistically significantly longer (1092 ± 657 seconds) compared to the control group (298 ± 81 seconds) and the group receiving 1 unit of botulinum-A toxin (439 ± 100 seconds) (P = .003). Furthermore, the BS EMG area under the curve values for the group receiving 5 units of botulinum-A toxin were significantly lower (7.4 ± 1.2 V/s × 10-4) than those of the control group (13.6 ± 4.0 V/s × 10-4) and the group receiving 1 unit of botulinum-A toxin (13.6 ± 5.0 V/s × 10-4) (P = .009). No statistically significant difference was found between the groups in terms of the basal SV pressure, number of SV phasic contractions, maximum amplitude of the SV phasic contraction, and intervals between the SV phasic contractions and the BS muscle contractions. CLINICAL IMPLICATIONS: Botulinum-A toxin injection is a potential treatment option for PE and should be further investigated by future clinical studies. STRENGTHS AND LIMITATIONS: Ease of administration and prolonged duration of botulinum-A toxin are advantages of the existing treatment options. The risk of anejaculation due to the dosage should be kept in mind. CONCLUSIONS: Injection of botulinum-A toxin into the BS muscle in rats significantly delayed the ejaculation latency time and affected the expulsion phase. Ongün S, Acar S, Koca P, et al. Can Botulinum-A Toxin Be Used to Delay Ejaculation: Results of an Ejaculation Model in Male Rats. J Sex Med 2019;16:1338-1343.

Impact of varicocelectomy on urine dopamine value in patients with premature ejaculation and varicocele.

Dopamine is an important regulator of male sexual function and behaviour. Decreased levels of this substance have been observed in blood and seminal plasma of infertile men. Hence, this study was carried out to determine the impact of varicocelectomy on 24-hr urine dopamine values in patients with both premature ejaculation (PE) and varicocele. In this prospective study, 55 consecutive patients with premature ejaculation and grade 2 or 3 varicocele were enrolled. The urine dopamine level was measured in a 24-hr sample by HPLC method in a single laboratory centre. Two samples were gathered from each patient, one before and the other 1 month after varicocelectomy. The mean initial and final 24-hr urine dopamine levels were 259.6 ± 86.3 and 602.9 ± 88.4 micrograms, respectively, showing statistically significant increase (p = .0001), while there was no statistically significant difference between urine volume and creatinine. However, the change in intravaginal ejaculation latency time value was not statistically significant at this short time visit. According to our findings, varicocelectomy results in a significant increase in 24-hr urine dopamine levels in patients with premature ejaculation and varicocele. However, the effect of this change on premature ejaculation in the long term has yet to be determined.

Efficacy and safety of dapoxetine for premature ejaculation: an updated systematic review and meta-analysis.

We conducted a systematic review and meta-analysis of published randomised controlled trials of dapoxetine for premature ejaculation. We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov and Clinical Trials.gov for studies reporting dapoxetine in men with premature ejaculation. Efficacy endpoints included intravaginal ejaculatory latency times (IELT), personal distress related to ejaculation (PDRE) and treatment-emergent adverse events (TEAEs) was used to evaluate safety. Data were analysed using a random-effects model. Electronic search identified 276 papers. The final analysis included eight papers (n = 8422 subjects). Analysis of the pooled results indicated efficacy in both IELT (weighted mean difference (WMD) = 1.67, 95% confidence interval (CI) 1.45-1.89) and PDRE (relative risk = 1.26, 95% CI 1.18-1.35). Subgroup analysis indicated efficacy (i.e. increase in IELT) for 30- and 60-mg on-demand dapoxetine (WMD 1.38 (95% CI 1.01-1.75) and 1.62 (95% CI 1.40-1.84) respectively), as well as daily use of 60 mg dapoxetine (WMD 2.18, 95% CI 1.71-2.64). The safety profile was acceptable. Based on the different effects of magnitude of the three dosing regimens, we recommend a stepwise approach, starting with 30 mg on demand, then 60 mg on demand and finally 60 mg dapoxetine daily.

[Correlation of betweenness centrality of the right hemispheric network with ejaculatory function in premature ejaculation patients].

OBJECTIVE: To explore the topological properties of the betweenness centrality of the nodes and edges in the brain white matter network of premature ejaculation (PE) patients and analyze the correlation of the importance of the key brain regions and interregional white matter structural connectivity with the ejaculatory function of the patients.Method: We collected the demographic and clinical data, along with the T1 and MR diffusion tensor imaging (MR-DTI) data, on 18 PE patients and 22 normal controls matched in age, sex and education. After preprocessing of the data obtained, we divided the whole brain into 90 symmetrical cortical and subcortical regions (defined as nodes of the brain network) by automated anatomical labeling, examined the structural connectivity between different brain regions by probabilistic white matter fiber tracking (defined as edges of the brain network), and calculated the betweenness centrality of the nodes and edges using the brain connection toolbox. Then, we performed the Mann-Whitney U test on the betweenness centrality of the nodes and edges, subjected the results to false discovery rate (FDR) correction, and assessed the correlation of the attribute values of between-group differences with the ejaculatory function of the patients. RESULTS: Compared with the normal controls, the PE patients showed a significantly decreased betweenness centrality of the right superior occipital gyrus (SOG) (281.18 ± 255.26 vs 67.78 ± 58.98, Z = －3.49, FDR-corrected P < 0.05), but increased betweenness centrality of the right superior temporal gyrus (STG) (222.91 ± 155.60 vs 557.00 ± 322.65, Z = 3.55, FDR-corrected P < 0.05) and betweeness centrality of the edge between the right rolandic operculum and right insula (4.23 ± 8.39 vs 23.83 ± 23.91, Z = 3.84, FDR-corrected P < 0.05). The betweenness centrality of the right SOG was correlated negatively with the level of difficulty in delaying ejaculation (r = －0.51, P = 0.03) and the probability of ejaculation before expectation (r= －0.61, P = 0.01), while that of the right STG positively with PE-related frustration (r = 0.54, P = 0.02) and the level of concern about PE-related distress of the partner (r = 0.47, P = 0.04). CONCLUSIONS: Abnormalities of structural connections were found in the visual stimulus- and emotion processing-related regions in the right cerebral hemisphere of PE patients, which might be associated with rapid ejaculation or decreased ejaculation control and lead to a series of psychological problems.

Alterations in cortical thickness in nonmedicated premature ejaculation patients: A morphometric MRI study.

PURPOSE: Premature ejaculation (PE) is one of the most common sexual dysfunctions in men. However, there has been little research evaluating alterations in brain structure related to PE. We aimed to investigate the characteristics of nonmedicated PE patients in terms of brain morphometry. MATERIALS AND METHODS: The sample consisted with 32 medication-naïve adult men with clinical diagnosed PE and matched 31 healthy controls. All participants received diagnostic interviews and 3.0 Tesla MRI scans. Automatic segmentation processing of MRI structure images was performed using FreeSurfer software and cerebral cortical thickness between groups was compared. RESULTS: The PE group had thicker cortex in widespread regions, including the frontal, parietal and occipital lobe, and limbic system, compared with the healthy control group (P < 0.05). Moreover, the duration is negatively correlated with the mean cortical thickness of the right medial orbitofrontal cortex, right precentral gyrus and left superior frontal cortex (R2 = 0.29, P < 0.003; R2 = 0.163, P < 0.04; R2 = 0.2, P < 0.02), while the Premature Ejaculation Diagnostic Tool score is negatively correlated with the mean cortical thickness of the left caudal middle frontal cortex (R2 = 0.33, P < 0.005). CONCLUSION: The result highlights the structural features of PE and suggests the relationship with the severity of impairment is related to the severity of anatomic abnormality with the relevant brain region. These results support the value of imaging measures as markers for understanding the physiopathology of PE. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:656-662.

Abnormal White Matter Microstructure in Lifelong Premature Ejaculation Patients Identified by Tract-Based Spatial Statistical Analysis.

INTRODUCTION: Several recent neuroimaging studies have identified functional and structural abnormalities in the cerebral cortex of lifelong premature ejaculation (LPE) patients, including task-related and resting-state brain function, and cortical thickness, although changes in white matter microstructure have not been reported. AIM: To assess the differences in white matter microstructure between LPE patients and healthy controls. METHODS: Diffusion tensor imaging (DTI) and tract-based spatial statistical analysis were used to detect differences in white matter microstructure between 32 LPE patients and 32 matched healthy controls. We also analyzed correlations of clinical indices with significant DTI-based features. MAIN OUTCOME MEASURES: DTI-based features (including fractional anisotropy [FA], mean diffusivity, axial diffusivity, and radial diffusivity) were assessed in LPE patients and controls, as well as the correlation of white matter changes in LPE patients with clinical data (including the premature ejaculation diagnostic tool score and the International Index of Erectile Function). RESULTS: LPE patients showed widespread increases in FA and axial diffusivity values compared with controls, including in the right posterior thalamic radiation, posterior corona radiata, bilateral posterior limb of the internal capsule, superior corona radiata, and external capsule. Further, FA in the right posterior thalamic radiation was positively correlated with the premature ejaculation diagnostic tool score in LPE patients. CLINICAL IMPLICATIONS: Changes of white matter microstructure may be an underlying marker for evaluating sensory conduction efficiency in LPE patients. STRENGTHS & LIMITATIONS: There are no previous studies examining white matter microstructure in LPE patients. The present study furthers our understanding of the etiology of LPE. Limitations include a cross-sectional study design without causal information, and no measurement of conduction efficiencies such as cortical somatosensory-evoked potential from the penis, or psychosocial factors. CONCLUSION: Our findings show potential microstructural white matter abnormalities related to LPE, suggesting that changes in fiber pathways connecting the cerebral cortex and the thalamus may play roles in the etiology of LPE. Gao M, Yang X, Liu L, et al. Abnormal White Matter Microstructure in Lifelong Premature Ejaculation Patients Identified by Tract-Based Spatial Statistical Analysis. J Sex Med 2018;15:1272-1279.