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Background Although 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. Aim To 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. Methods Data 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 Measures The 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. Results Patients 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 Implications If 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 & Limitations This 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. Conclusion This 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.

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.

Introduction Cligosiban is an orally administered, centrally penetrant oxytocin receptor antagonist being developed to treat premature ejaculation (PE). Aim To 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. Methods Patients 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 Measure Efficacy 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. Results There 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 Implications This 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 Limitations This 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. Conclusions Cligosiban was well tolerated but failed to demonstrate efficacy for the treatment of men with lifelong PE at doses up to 1200 mg.

Introduction Even though lifelong premature ejaculation (PE) is highly prevalent, few studies have investigated the neural mechanisms underlying PE. Aim This study aimed to investigate whether patients with lifelong PE exhibit macrostructural or microstructural alterations of the parts of the brain involved in the male sexual response. Materials and Methods We enrolled 42 healthy participants and 54 lifelong PE patients. Lifelong PE was diagnosed according to the Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculation latency time (IELT). We compared measures of cortical morphology, such as volumes of gray matter, white matter, cerebellum volumes, and subcortical structures (ie, amygdala, caudate, hippocampus, globus pallidus, putamen, and thalamus) between the groups using a voxel-based morphometry method from whole-brain T1-weighted magnetic resonance imaging. Moreover, we evaluated the relationships between the relevant cerebral alterations and the severity of symptoms obtained from participants via self-reported questionnaires. Main Outcome Measures Cerebral macrostructural and microstructural alterations were assessed in PE patients and controls, along with the correlation of caudate nucleus changes in PE patients with clinical data (including the PEDT and the IELT). Results The mean volume of the caudate nucleus was significantly larger in the lifelong PE patients compared with healthy controls (P = .048). Moreover, caudate nucleus volume was positively correlated with PEDT score (r = 0.621; P = .0179) and negatively correlated with the IELT (r = −0.592; P = .0101). However, cortex morphology and the other subcortical volumes were not significantly different between the 2 groups (P > .05). Clinical Implications Microstructural alterations in deep gray matter nuclei might be a useful parameter for studying the mechanism of the neurobiology underlying PE. Strengths and Limitations There are few studies examining microstructural changes in PE patients. This study furthers our understanding of the etiology of PE. Limitations include the small sample, which limits our ability to make an absolute determination as to whether such subcortical changes are the cause or the consequence of lifelong PE. Conclusions We found a significant difference in caudate nucleus volume between patients with PE and healthy controls. In addition, the caudate nucleus volume was positively associated with the severity of PE symptoms. More extensive and possibly longitudinal studies are needed to improve our understanding of the mechanism of the neurobiology underlying PE.

Background Alpha-adrenergic antagonist treatment for benign prostatic hyperplasia (BPH) and drug-related sexual side effects are frequent in aging men. Aim To investigate functional changes in erectile and ejaculatory aspects of male sexuality under Silodosin 8 mg per day treatment for BPH. Methods Sexually active patients diagnosed with BPH and who initiated Silodosin treatment were the subjects of the study. The International Prostate Symptom Score, premature ejaculation patient profile (PEP-male) questionnaire, Sexual Health Inventory for Men (SHIM) questionnaire, and estimated intravaginal ejaculation latency time (IELT) values of the participants were used to evaluate sexual functions. Data evaluation was performed in 8 urology clinics retrospectively. Outcomes Participant ratings for SHIM, PEP, and estimated IELT were the primary outcome measures in the study. Results Among 187 recruited patients, data of 98 patients, who completed the trial period in the study, were eligible. The median age of the eligible participants who completed the trial period for 3 months was 59.5 years (range 45–82). 16 patients of 187 (8%) reported a desire for drug withdrawal for anejaculation during the recruitment period. 46 (46.9%) and 49 (50%) patients reported anejaculation in the first and third month of the treatment, respectively. De novo erectile dysfunction was noticed in 15 patients (15.3%). There was a significant increase in the estimated IELT of subjects in both the first (P = .01) and third (P = .002) month. SHIM-1 (P = .008), SHIM-total (P = .009), and PEP scores (P = .008) were also improved in the third month of the treatment. Neither baseline patient characteristics nor changes in the International Prostate Symptom Score after treatment predicted final outcomes with multivariable analysis. The subgroup analysis of participants who reported “anejaculation” also revealed better outcomes compared with participants ejaculating naturally in the third month as per SHIM ratings. Clinical Implications Despite several male patients having dry orgasms due to Silodosin-induced anejaculation, the majority experienced improved erectile function. Strengths & Limitations The present study demonstrated pioneering results while investigating both erectile and ejaculatory dimensions of the male sexual function during Silodosin treatment for BPH. However, lack of partner evaluation, low follow-up rates, and lack of knowledge about reasons why subjects are lost to follow-up after drug initiation have limited our interpretation. Conclusion Most patients using Silodosin 8 mg per day for BPH treatment experienced improvement in their erectile function, estimated IELT, and premature ejaculation profile in the third month of the treatment. Underlying mechanisms and reasons for individual differences necessitate further investigation.

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.

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 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.

A new classification of premature ejaculation (PE) has been proposed, including the categories of lifelong PE (LPE), acquired PE (APE), natural variable PE (NVPE), and premature-like ejaculatory dysfunction (PLED).The aim of this study was to evaluate the impact of intravaginal ejaculation latency time (IELT) and erectile function on anxiety and depression among patients with PE in general and according to the four types of PE.Between September 2011 and September 2012, we conducted a cross-sectional study in the Anhui province of China. We enrolled 4,000 men aged over 18 years, each of whom had been in a stable, monogamous, heterosexual relationship with the same partner for at least 6 months.Self-estimated IELT, the International Index of Erectile Function-5 (IIEF-5) and the Zung Self-Rating Anxiety and Depression Scales (SAS/SDS) were used to measure PE, erectile dysfunction (ED), anxiety, and depression, respectively, among the entire study population.Of the 3,016 men evaluated, 25.80% complained of PE. Distribution of the four types of PE among men with PE was as follows: LPE, 12.34%; APE, 18.77%; NVPE, 44.09%; PLED, 24.81%. Men with PE presented lower IIEF-5 scores and higher SAS and SDS scores vs. men without PE (P0.001 for all). Similar findings were observed in men with APE when compared with other PE syndromes. After adjustment for age in men with PE, IELT was negatively associated with SAS and SDS scores (SAS, adjusted r = -0.42, P0.001; SDS, adjusted r = -0.45, P0.001). IIEF-5 score was negatively associated with SAS and SDS scores (SAS, adjusted r = -0.54, P0.001; SDS, adjusted r = -0.50, P0.001). These negative relationships were strongest in men with PLED (IELT vs. SAS: adjusted r = -0.63, P0.001; IELT vs. SDS, adjusted r = -0.60, P0.001; IIEF-5 vs. SAS: adjusted r = -0.57, P0.001; IELT vs. SDS, adjusted r = -0.55, P0.001).APE patients reported higher rates of ED, anxiety, and depression than men with other types of PE. The negative relationships between IELT/IIEF-5 and SAS/SDS were strongest in men with PLED.

Introduction Although 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. Aims We investigated the prevalence and factors associated with the complaint of PE and the four PE syndromes in Anhui province, China. Methods Between 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 Measures PE 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. Results Of 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 P = 0.012, cardiovascular P = 0.003, others P P Conclusion The 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.

Introduction. Ejaculatory/orgasmic disorders are common male sexual dysfunctions, and include premature ejacu- lation (PE), inhibited ejaculation, anejaculation, retrograde ejaculation, and anorgasmia. Aim. To provide recommendations and guidelines concerning current state-of-the-art knowledge for management of ejaculation/orgasmic disorders in men. Methods. An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 25 committees. Committee members estab- lished specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge of disorders of orgasm and ejaculation represent the opinion of seven experts from seven countries developed in a process over a 2-year period. Main Outcome Measure. Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. Results. Premature ejaculation management is largely dependent upon etiology. Lifelong PE is best managed with PE pharmacotherapy (selective serotonin re-uptake inhibitor (SSRI) and/or topical anesthetics). The management of acquired PE is etiology specific and may include erectile dysfunction (ED) pharmacotherapy in men with comorbid ED. Behavioral therapy is indicated when psychogenic or relationship factors are present and is often best combined with PE pharmacotherapy in an integrated treatment program. Retrograde ejaculation is managed by education, patient reassurance, pharmacotherapy, or bladder neck reconstruction. Delayed ejaculation, anejaculation, and/or anorgasmia may have a biogenic and/or psychogenic atiology. Men with age-related penile hypoanesthesia should be educated, reassured, and instructed in revised sexual techniques which maximize arousal. Conclusions. Additional research is required to further the understanding of the disorders of ejaculation and orgasm. Rowland D, McMahon CG, Abdo C, Chen J, Jannini E, Waldinger MD, and Ahn TY. Disorders of Orgasm and Ejaculation in Men. J Sex Med 2010;7:1668-1686.

Introduction The intravaginal ejaculation latency time (IELT) behaves in a skewed manner and needs the appropriate statistics for correct interpretation of treatment results. Aims 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. Methods Linking theoretical arguments to the outcome of several selective serotonin reuptake inhibitor and modern antidepressant study results. Main Outcome Measures Geometric mean IELT and fold increase of geometrical mean IELT. Results 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. Conclusions 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. Waldinger MD, Zwinderman AH, Olivier B, and Schweitzer DH. Geometric mean IELT and premature ejaculation: Appropriate statistics to avoid overestimation of treatment efficacy.

Introduction. Premature ejaculation (PE) is a worldwide problem without an approved treatment. Selective sero- tonin reuptake inhibitors (SSRIs) are widely used "off label" as pharmacotherapeutic agents in the treatment of PE. Aim. This study investigates Tramadol efficacy for on-demand treatment of PE. Main Outcomes Measures. Intravaginal ejaculation latency time (IELT) was used as an objective tool to assess the efficacy of the investigated treatments. Materials and Methods. Single-blind, placebo-controlled, crossover, stopwatch monitored two-period study was conducted, on 60 patients with lifelong PE. PE was defined as IELT of < 2 minutes in 80% of intercourse episodes. A total of 25 mg of Tramadol hydrochloride was given to one group (30) prior to intercourse and placebo was supplied for the other group (30) for 8 weeks. Drugs were taken 1-2 hours before sexual activity and sexual intercourse was required at least once per week. After the initial treatment period, the two groups took the alternate medication for another 2 months. The two 8-week treatment periods were separated by 1 week washout period. IELT was timed by a stopwatch at each intercourse and was reported by patients or partners. Results. The baseline (mean ± SD) IELT for patients before treatment was 1.17 ± 0.39 minutes. At the end of the treatment period utilizing the active drug, the mean IELT was increased significantly in patients on Tramadol treatment to 7.37 ± 2.53 minutes. The same patients on placebo medication had mean IELT of only 2.01 ± 0.71 minutes. Patients uniformly reported satisfaction with their resulting control over ejaculation. Conclusions. Tramadol, a drug with a proven safety record as an anti-inflammatory agent, shows promise as a drug for treating rapid ejaculation. Salem EA, Wilson SK, Bissada NK, Delk JR II, Hellstrom WJ, and Cleves MA. Tramadol HCL has promise in on-demand use to treat premature ejaculation. J Sex Med 2008;5:188-193.

Introduction Lifelong premature ejaculation (LPE) is the most important ejaculating dysfunction. Relatively little is known about erectile function in this population. Aims We 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. Methods A 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 Measures The 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). Results Of 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. Conclusions Bias 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.

Background In former days, information obtained from randomized well‐controlled clinical trials and epidemiological studies on premature ejaculation (PE) was not available, thereby hampering the efforts of the consecutive DSM Work Groups on Sexual Disorders to formulate an evidence‐based definition of PE. The current DSM‐IV‐TR definition of PE is still nonevidence based. In addition, the requirement that persistent self‐perceived PE, distress, and interpersonal difficulties, in absence of a quantified ejaculation time, are necessary to establish the diagnosis remains disputable. Aim To investigate the validity and reliability of DSM and ICD diagnosis of premature ejaculation. Methods The historical development of DSM and ICD classification of mental disorders is critically reviewed, and two studies using the DSM‐IV‐TR definition of PE is critically reanalyzed. Results Reanalysis of two studies using the DSM‐IV‐TR definition of PE has shown that DSM‐diagnosed PE can be accompanied by long intravaginal ejaculation latency time (IELT) values. The reanalysis revealed a low positive predictive value for the DSM‐IV‐TR definition when used as a diagnostic test. A similar situation pertains to the American Urological Association (AUA) definition of PE, which is practically a copy of the DSM‐IV‐TR definition. Conclusion It should be emphasized that any evidence‐based definition of PE needs objectively collected patient‐reported outcome (PRO) data from epidemiological studies, as well as reproducible quantifications of the IELT. Waldinger MD, and Schweitzer DH. Changing paradigms from a historical DSM‐III and DSM‐IV view toward an evidence‐based definition of premature ejaculation. Part I—Validity of DSM‐IV‐TR. J Sex Med 2006;3:682–692.

Background. In the Diagnostic and Statistical Manual of Mental Disorders (DSM), a descriptive definition for premature ejaculation (PE) that was based on historical assumptions has been accepted. Aim. To formulate a new functional definition of PE in the DSM. Methods. A "syndrome" approach instead of a "complaint" approach is applied and evidence-based data from epidemiological and clinical studies are used. Results. A new functional definition of PE should pertain to a cluster of "symptoms" of a distinct "syndrome." A syndrome rather than a descriptive definition should distinguish Lifelong and Acquired PE variants. Evidence-based data also suggest another PE type "Natural Variable PE," which is not a typical syndrome but rather a cluster of inconsistent symptoms of rapid ejaculation. Moreover, in "Natural Variable PE" the occurrence of rapid ejaculation is not based on neurobiological or psychological pathology, but belongs to the normal variability of sexual perfor- mance. Its prevalence is probably much higher than that of Lifelong and Acquired PE. We propose three separate operationalized definitions of these three PE types for the pending DSM-V and ICD-11, which include a quanti- fication of the ejaculation time (intravaginal ejaculation latency time), inability of ejaculatory control, and a descrip- tion of severity of PE in terms of psychological distress. Conclusion. The use of the intravaginal ejaculation latency time into the DSM-V and ICD-11 would mean that statistical evidence becomes accepted as one of the mainstays for establishing an evidence-based definition of the three PE types. Waldinger MD, and Schweitzer DH. Changing paradigms from a historical DSM-III and DSM-IV view toward an evidence-based definition of premature ejaculation. Part II—Proposals for DSM- V and ICD-11. J Sex Med 2006;3:693-705.

Introduction Apart from the involvement of central serotonergic neurotransmission on lifelong premature ejaculation, interference of thyroid function has been speculated. Aim To study thyroid function in a large group of men with lifelong premature ejaculation (LPE). Methods Lifelong premature ejaculation was defined as an intravaginal ejaculation latency time (IELT) of less than 1 minute. Any consecutive man with LPE and no erectile dysfunction assessed by medical history and the International Index of Erectile Function (IIEF‐5) was eligible for the study. Apart from the assessment of thyroid‐stimulating hormone (TSH) also free thyroxin (f T 4 ) was determined in case of a TSH of 4.0 mU/L (being the lower and upper limits of normal values, respectively). Blood samples were drawn throughout the day within office hours. Main Outcome Measures Thyroid‐stimulating hormone and f T 4 . Results Included were 620 men; age (mean ± SD) was 39.9 ± 9.4 years (range 19–65). TSH concentrations from morning, early and late afternoon samples did not differ. The geometrical mean TSH concentration was 0.85 mU/L (95% confidence intervals: 0.82–0.90) with a coefficient of variation of 57.9%. Fourteen men had a TSH of 4.0 mU/L. All men with an abnormal TSH had a normal f T 4 (between 10 and 20 pmol/L). No relationship was found between age and TSH concentrations. Conclusion. Thyroid‐stimulating hormone distribution was analyzed in a cohort of Dutch men with lifelong premature ejaculation and no erectile dysfunction. According to statistical analysis, there appeared to be no interaction between this ejaculatory complaint and the prevalence of thyroidal dysfunction. However, further studies are needed to gain more insight into the role of thyroid dysfunction and regulation of ejaculation time. Waldinger MD, Zwinderman AH, Olivier B, and Schweitzer DH. Thyroid‐stimulating hormone assessments in a Dutch cohort of 620 men with lifelong premature ejaculation without erectile dysfunction. J Sex Med 2005;2:865–870.

Introduction Intravaginal ejaculation latency time (IELT), defined as the time between the start of vaginal intromission and the start of intravaginal ejaculation, is increasingly used in clinical trials to assess the amount of selective serotonin reuptake inhibitor-induced ejaculation delay in men with premature ejaculation. Prospectively, stopwatch assessment of IELTs has superior accuracy compared with retrospective questionnaire and spontaneous reported latency. However, the IELT distribution in the general male population has not been previously assessed. Aim To determine the stopwatch assessed-IELT distribution in large random male cohorts of different countries. Methods A total of 500 couples were recruited from five countries: the Netherlands, United Kingdom, Spain, Turkey, and the United States. Enrolled men were aged 18 years or older, had a stable heterosexual relationship for at least 6 months, with regular sexual intercourse. The surveyed population were not included or excluded by their ejaculatory status and comorbidities. This survey was performed on a "normal" general population. Sexual events and stopwatch-timed IELTs during a 4-week period were recorded, as well as circumcision status and condom use. Main outcome measures The IELT, circumcision status, and condom use. Results The distribution of the IELT in all the five countries was positively skewed, with a median IELT of 5.4 minutes (range, 0.55-44.1 minutes). The median IELT decreased significantly with age, from 6.5 minutes in the 18-30 years group, to 4.3 minutes in the group older than 51 years (P Conclusion The IELT distribution is positively skewed. The overall median value was 5.4 minutes but with differences between countries. For all five countries, median IELT values were independent of condom usage. In countries excluding Turkey, the median IELT values were independent of circumcision status.

Introduction Consensus on a definition of premature ejaculation has not yet been reached because of debates based on subjective authority opinions and nonstandardized assessment methods to measure ejaculation time and ejaculation control. Aim To provide a definition for lifelong premature ejaculation that is based on epidemiological evidence including the neurobiological and psychological approach. Methods We used the 0.5 and 2.5 percentiles as accepted standards of disease definition in a skewed distribution. We applied these percentiles in a stopwatch‐determined intravaginal ejaculation latency time (IELT) distribution of 491 nonselected men from five different countries. The practical consequences of 0.5% and 2.5% cutoff points for disease definition were taken into consideration by reviewing current knowledge of feelings of control and satisfaction in relation to ejaculatory performance of the general male population. Main Outcome Measures Literature arguments to be used in a proposed consensus on a definition of premature ejaculation. Results The stopwatch‐determined IELT distribution is positively skewed. The 0.5 percentile equates to an IELT of 0.9 minute and the 2.5 percentile an IELT of 1.3 minutes. However, there are no available data in the literature on feelings of control or satisfaction in relation to ejaculatory latency time in the general male population. Random male cohort studies are needed to end all speculation on this subject. Exact stopwatch time assessment of IELT in a multinational study led us to propose that all men with an IELT of less than 1 minute (belonging to the 0.5 percentile) have “definite” premature ejaculation, while men with IELTs between 1 and 1.5 minutes (between 0.5 and 2.5 percentile) have “probable” premature ejaculation. Severity of premature ejaculation (nonsymptomatic, mild, moderate, severe) should be defined in terms of associated psychological problems. Conclusion We define lifelong premature ejaculation as a neurobiological dysfunction with an unacceptable increase of risk to develop sexual and psychological problems anywhere in a lifetime. By defining premature ejaculation from an authority‐defined disorder into a dysfunction based on epidemiological evidence it is possible to establish consensus based on epidemiological evidence. Additional epidemiological stopwatch studies are needed for a final decision of IELT values at both percentile cutoff points.

Introduction. Premature ejaculation (PE) is the most common male sexual dysfunction affecting men and their partners. Lack of community-based data describing this condition limits understand- ing of PE and its outcomes. Aim. To characterize PE in a large population of men with and without PE using patient-reported outcome (PRO) measures elicited from men and their partners. Methods. 4-week, multicenter, observational study of males ( ≥ 18 years) and their female partners in monogamous relationships ( ≥ 6 months). Screening, baseline, and follow-up visits scheduled at 2-week intervals. Clinicians diagnosed PE utilizing DSM-IV-TR criteria. Intravaginal ejaculatory latency time (IELT), measured by a stopwatch held by the partner, was recorded for each sexual intercourse experience. Subject and partner independently assessed PROs: control over ejaculation and satisfaction with sexual intercourse (0 = very poor to 4 = very good), personal distress and interper- sonal difficulty (0 = not at all to 4 = extremely), and severity of PE (0 = none to 3 = severe). Results. Of the total study population (N = 1,587), 207 subjects were diagnosed with PE and 1,380 were assigned to the non-PE group. Median IELT (min) was 1.8 (range, 0-41) for PE and 7.3 (range, 0-53) for non-PE subjects ( P < 0.0001). More PE vs. non-PE subjects gave ratings of "very poor" or "poor" for control over ejaculation (72% vs. 5%; P < 0.0001) and satisfaction with sexual intercourse (31% vs. 1%; P < 0.0001). More subjects in the PE vs. non-PE group gave ratings of "quite a bit" or "extremely" for personal distress (64% vs. 4%; P < 0.0001) and interpersonal difficulty (31% vs. 1%; P < 0.0001). Subject and partner assessments showed similar patterns and correlated moderately (0.36-0.57). Conclusions. PE subjects reported significantly shorter IELT. Overlap in IELT distributions was observed between the PE and non-PE groups, indicating the need for additional PRO measures to characterize PE. Shorter IELT was significantly associated with reduced ejaculatory control and sexual satisfaction and increased distress and interpersonal difficulty.

Background In our previous study, significantly higher antioxidant enzymes and malondialdehyde (MDA) levels in patients with premature ejaculation (PE) compared to healthy controls were found. In the present study, we planned to evaluate antioxidant enzymes and MDA levels of patients with PE before and after citalopram treatment. Methods The study comprised 30 patients with PE according to Diagnostic and Statistical Manual of Mental Disorders Fourth Version (DSM‐IV) and 30 healthy controls. The patients were randomly assigned to two groups. Fifteen of them (group I) received 8 weeks of citalopram treatment but the remaining (group II) did not. The subjects were asked to determine the average intravaginal ejaculation latency time (IVELT). The fasting antioxidant enzymes and MDA levels were measured at baseline and after 8 weeks. Results No statistically significant difference in the mean IVELT between groups at baseline was found. IVELT considerably elevated after 8 weeks of citalopram treatment in group I with a mean of 209 ± 72.1 seconds but not in group II. Antioxidant enzymes and MDA levels did not differ between groups at baseline. At the evaluation of week 8, SOD, GSH‐Px, and MDA levels significantly reduced during treatment in group I patients. Conclusion In conclusion, the results suggest that the ability for antioxidant enzymes and MDA to normalize through symptom alleviation reveals that they might be trait marker of PE. Further placebo‐controlled studies are needed.

Introduction Recently, the idea has emerged that on‐demand use of serotonin reuptake inhibitors (SSRIs), particularly short half‐life, should be equally effective in delaying ejaculation as daily SSRI treatment of premature ejaculation. Aim To provide evidence that SSRI‐induced ejaculation delay is mainly dependent on pharmacodynamic properties of the drug and hardly on pharmacokinetic factors, and that combined SSRI administration with specific 5‐hydroxytryptamine (5‐HT) receptor antagonism leads acutely to stronger ejaculation delay than acute SSRI monoadministration. Methods We performed a detailed analysis of serotonin neurotransmission and reviewed animal studies with 5‐HT 1A receptor antagonists. In addition, we critically reviewed existing on‐demand SSRI treatments publications and the current debate on a definition of premature ejaculation. Main Outcome Measures Intravaginal ejaculation latency time (IELT). Results Acute SSRI administration leads to only a mild or no increase of 5‐HT neurotransmission and concomitant stimulation of postsynaptic 5‐HT receptors. Existing on‐demand SSRI treatment studies suffer from methodological insufficiencies, and the reported high‐fold increases of ejaculation time contradict with neuropharmacological insights from serotonin metabolism. Animal studies show that SSRI coadministration with 5‐HT 1A receptor antagonists significantly increases the ejaculation time acutely compared to acute SSRI monoadministration. Conclusion On‐demand SSRI treatment has less ejaculation‐delaying effects than daily SSRI treatment. SSRIs with a short half‐life are likely leading to much less ejaculation delay than current registered SSRIs. Combined use of SSRIs with 5‐HT 1A receptor antagonists increases the likelihood of clinically relevant ejaculation delay after on‐demand treatment. On‐demand SSRIs with short half‐life that insufficiently delay ejaculation in men with IELTs less than 1 minute should be called ejaculation‐delaying drugs rather than drugs against premature ejaculation.

Introduction The pathologic mechanisms of primary premature ejaculation (PPE) are complex and multifactorial, and hyperactivity of the sympathetic nervous system is one of the mechanisms. Aim To 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. Methods Sixty‐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 Measures Changes 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. Results Overall, 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 P 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). Conclusions These 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.

The duration of the intravaginal ejaculation latency time (IELT) may give rise to subjective complaints of premature ejaculation (PE) and is usually determined by self-assessment or by stopwatch.The aim of this study was to investigate the IELT distribution in the general male population and the accuracy of IELT assessment by using a blinded timer device instead of a stopwatch, thereby minimizing possible interference with the spontaneous and natural way of having intercourse.The IELT was measured with a timer device during 4 weeks in a nonselected sample of 474 men from The Netherlands, Spain, United Kingdom, Turkey, and the United States. Questionnaires were administered before and after the 4-week IELT assessments.IELT; erectile function dysfunction score of International Index of Erectile Dysfunction (IIEF).The IELT had a positively skewed distribution, with a geometric mean of 5.7 minutes and a median of 6.0 minutes (range: 0.1-52.1 minutes). Men from Turkey had the shortest median IELT (4.4 minutes). Men from the United Kingdom had the longest IELT (10.0 minutes). Circumcision and condom use had no significant impact on the median IELT. Subjects who were discontent with their latency time had slightly lower median IELT values of 5.2 minutes than the median of the population.The IELT distribution, measured with a blinded timer device, is very similar to the IELT distribution of our previous population survey which utilized a stopwatch. In the general male population, complaints of discontent with self-perceived latency had a slightly lower median IELT value than the median of the overall population.

Introduction 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. Aim 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. Methods 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. Results 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. Conclusions 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. Waldinger MD, and Schweitzer DH. Premature ejaculation and pharmaceutical company-based medicine: The dapoxetine case.

Introduction The DSM-III definition of premature ejaculation (PE) contains the criterion “control” but not that of “ejaculation time.” In contrast, the Diagnostic and Statistical Manual of Mental Disorders (4th edition, Text Revision) (DSM-IV-TR) contains the criterion “short ejaculation time,” while it lacks “control.” Aim To review the adequacy and consequent use of all criteria of the DSM-IV-TR definition in previously published PE Internet surveys. Methods Reviewing all published cohort studies on PE from 2004 to 2007. MEDLINE and EMBASE computer bibliographies were used. Main Outcome Measure Definitions of DSM-III, DSM-IV-TR, and International Classification of Diseases. Results Five papers, of which three are original studies, reported inclusion of men with PE according to DSM-IV-TR definition but omitted to apply the required “short ejaculation time” criterion. These studies, which have defined PE according to subjective criteria such as control, actually referred to the DSM-III definition. Using DSM-III-like definitions in three different studies revealed a highly variable prevalence of PE (32.5%, 27.6%, and 13.0%). In contrast, based on studies using a 1-minute cutoff point, being the time that is required to call ejaculation time “short” or using the criterion “persistent occurrence,” PE revealed to be far less prevalent (5–6%). Conclusions Unacceptable discrepancies of PE definitions according to DSM-III (abandoned but still used) and DSM-IV-TR argue strongly in favor of a multidimensional new classification of PE for the DSM-V. Waldinger MD, and Schweitzer DH. The use of old and recent DSM definitions of premature ejaculation in observational studies: A contribution to the present debate for a new classification of PE in the DSM-V.

Introduction Premature ejaculation (PE) is the most prevalent sexual dysfunction among men. Several theories about its etiology have been made. One of the conflicting factors is the effect of circumcision on ejaculation, and there are some concerns about leaving so much mucosa during circumcision. Aim In our study the relationship between mucosal cuff length and PE was investigated. Methods Eighty-four circumcised men were studied, including 42 men with PE and 42 men without. The following data and measurements were investigated: age, education, smoking, intravaginal ejaculation latency time (IELT), circumcision timing, stretched penile, penile skin, and mucosal cuff lengths. Main Outcome Measure Penile, mucosal cuff, and penile skin lengths, the IELT. Results The mean penile, mucosal cuff, and penile skin lengths were 121.1 ± 12.8, 15.4 ± 4.8, and 80.8 ± 21.0 mm in PE men, respectively, and were 130.1 ± 10.4, 14.7 ± 3.4, and 88.7 ± 12.2 mm in the control group, respectively. No statistically significant differences were seen regarding the length of the penis ( P = 0.80), mucosal cuff ( P = 0.84), and penile skin ( P = 0.99). The two groups were not different regarding education ( P = 0.90), smoking ( P = 0.70), and circumcision timing ( P = 0.65). Conclusion Postcircumcision mucosal cuff length is not a risk factor for PE. Hosseini SR, Khazaeli MH, and Atharikia D. Role of postcircumcision mucosal cuff length in lifelong premature ejaculation: A pilot study.

Introduction Sexual problems are common in the general population. Studies have shown that most of these sexual problems are related to their social lives, medical illnesses, and psychological status. Among the sexual problems in men, premature ejaculation (PE) is one of the most frequent, yet it is the least well-understood of the sexual dysfunctions of men. Aim To determine the prevalence of sexual problem particularly PE and erectile dysfunction (ED) among people living in urban areas and to investigate the characteristics associated with these sexual problems in a Malaysian population. Main Outcome Measure The PE which is defined as an intravaginal ejaculation latency time less than 2 minutes was assessed in the ED and non-ED group. Methods The Hospital Anxiety and Depression scale is used as a measure of the psychological status [30]. The ED status was assessed using the International Index of Erectile Function questionnaire. Results The prevalence of self-reported sexual problems for ED and PE were 41.6% and 22.3%, respectively. In those subjects with ED, 33.5% reported to have PE. Of the total of 430 subjects, anxiety was present in 8.1%, while depression was 5.3%. The prevalence of PE accounted for 25% anxiety and 14.6% for depression respectively in the population. EDs were associated with diabetes and hypertension (OR [95% CI]: 5.33 [2.33, 10.16], 3.40 [1.76, 6.57], P Conclusion Prevalence of ED is associated with medical symptoms such as diabetes and hypertension and a rise in the prevalence of age while psychological distress such as anxiety and depression also contribute to a higher PE rate. Quek KF, Sallam AA, Ng CH, and Chua CB. Prevalence of sexual problems and its association with social, psychological and physical factors among men in a Malaysian Population: A cross-sectional study.

Background Although premature ejaculation (PE) is a common male sexual dysfunction, its relevant parameters have not been adequately studied in large community‐based samples. Objective To examine the diagnostic utility of two self‐report questions based on the DSM‐IV‐TR definition of PE and to investigate the relationship between self‐identified PE, sexual functioning, and sexual satisfaction in men. Methods An Internet survey of general health and aspects of sexual functioning and satisfaction was conducted in 2056 males. Subjects were classified as having “probable” or “possible” PE, or as “non‐PE” by survey responses. Results A total of 1158 men met the selection criteria (sexually active in a stable heterosexual relationship), and 189 (16.3%) were classified as having probable PE by reporting they ejaculated before they wished and indicating it was “very much” or “somewhat” a problem. Another 188 (16.2%) men reported ejaculating before they wished but rated their distress lower and were classified as having possible PE. Compared to non‐PE men, those with probable and possible PE reported significantly worse sexual functioning in 6 of 8 study measures. Concern about partner satisfaction was high in all groups. The importance of ejaculatory control and the ability to have intercourse for the desired time was significantly higher in men with PE as compared to non‐PE men ( P Conclusions PE was a common problem, was characterized by a lack of ejaculatory control, and was associated with significant effects on sexual functioning and satisfaction. Additional research on the sensitivity and specificity of these self‐report questions should be pursued.