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Lifelong premature ejaculation (LPE) may have heritable components. Selective serotonin reuptake inhibitors have been proven effective in prolonging intravaginal ejaculation latency time (IELT). Given that serotonergic pathways are involved in the ejaculation mechanism, we aimed to investigate whether His452Tyr, also known as the C1354T (RS6314) polymorphism of the 5-HT2A receptor, contributes to LPE pathogenesis and IELT differences among patients with LPE. Dutch Caucasian men with LPE (n = 65) attending the Outpatient Department of Neurosexology, HagaZiekenhuis for drug treatment for LPE in 2009 were selected and included in this case-control study. IELT during coitus was measured using a stopwatch, and all men were genotyped for the His452Tyr polymorphism. Analysis of variance (ANOVA) was performed to determine the association between the genotypes and IELTs. Mean IELTs with standard deviations were 29.7 (+/- 20.9), 31.5 (+/- 14.7), and 26.0 s, and the frequencies were 83.1%, 15.4%, and 1.5% for the CC, CT, and TT groups, respectively, with an average IELT of 29.9 s. No difference in mean IELT was observed between these groups. In the affected group, the frequencies of alleles C and T were 90.8% and 9.2%, respectively; whereas those among randomly selected European Caucasian male controls (n = 503) from the CEPH database were of 92.0% and 8.0%, respectively. No significant difference was observed between the groups. Therefore, no correlation was found between the His452Tyr polymorphism and IELT distribution in patients with LPE.

BACKGROUND: Lifelong premature ejaculation (PE) is one common male sexual dysfunction and is implicated in widespread structural and functional abnormalities of bilateral hemispheres. However, whether the inter-hemisphere functional connectivity (FC) of lifelong PE patients was altered still remain unclear. METHODS: Thirty-four lifelong PE patients and 30 healthy controls (HCs) were enrolled in this study and all underwent T1-weighted and resting-state functional MRI (fMRI) scan. The voxel-mirrored homotopic connectivity (VMHC) measure and independent sample t-test were applied to examine the alterations of VMHC values in the patients relative to HCs with the significant threshold at P

Objective: The intravaginal ejaculatory latency time (IELT) may increase less in on-demand compared to daily intake, but may fulfill a suitable treatment for specific patients. We decided to compare the efficacy and safety of on-demand and daily use of sertraline in order to find the most effective and least complicated method in treatment of premature ejaculation (PE). Methods: This study was parallel or concurrent control randomized clinical trial. Two hundred and forty patients with PE diagnosed by urologist in the two groups of 120 from July 2017 to February 2019 enrolled in the study. In the first group, it is prescribed 50 mg sertraline each 12 h daily and the second group received 50 mg 4 h before coitus for 4 and 8 weeks. The IELT before treatment and during all coitus after treatment were recorded by the patient's wife with a stopwatch. Results: Mean IELT before, 4 and 8 weeks after treatment in two groups were: On-demand group 101.62±65.44 s, 208.75±128.02 s and 265.87±145.70 s; daily use group 102.50±81.22 s, 276.87±181.08 s and 353.75±176.45 s, respectively. The ejaculation time increased significantly in both groups (p

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.

Context: Premature ejaculation (PME) is a common sexual disorder. Drugs used commonly used for its treatment have various side effects and disadvantages. Yoga is being increasingly studied in a variety of medical disorders with positive results. However, its evidence for patients with PME is very limited. Aims: The aims of this study were to investigate the effect of yoga on ejaculation time in patients with PME and to compare it with paroxetine. Settings and Design: This was a nonrandomized nonblinded comparative study in a tertiary care center. Materials and Methods: Among patients with PME, 40 selected paroxetine and 28 yoga. Intravaginal ejaculation latency time (IELT) was measured in seconds once before and three times after intervention. Statistical Analysis Used: Mean, standard deviation, paired and unpaired t-tests, and repeated measures ANOVA were used for statistical analysis. Results: IELT was significantly increased in both groups – paroxetine (from 29.85 ± 11.9 to 82.19 ± 32.9) and yoga (from 25.88 ± 16.1 to 88697 + 26.9). Although the effect of yoga was slightly delayed in onset, its effect size (η2 = 0.87, P < 0.05) was more than paroxetine (η2 = 0.73, P < 0.05). One-fifth of the patients in the paroxetine group (19.5%) and 8% in the yoga group continued to have the problem of PME at the end of the trial. Conclusions: Yoga caused improvement in both intravaginal ejaculation latency time and subjective sexual experience with minimal side effect. Therefore, yoga could be an easily accessible economical nonpharmacological treatment option for the patient with PME.

Introduction Premature ejaculation (PE) is widely regarded as one of the most common sexual dysfunctions in men. The neurobiogenesis of PE is complex and involves the serotoninergic (5-HT) system. Aim In this study, we investigated whether polymorphisms in the tryptophan hydroxylase 2 (TPH2) gene were associated with lifelong PE (LPE). Methods A total of 121 men diagnosed with LPE were recruited from our outpatient clinics and 94 healthy controls from the health examination center. Intravaginal ejaculation latency time (IELT) was measured using a stopwatch. The PE diagnostic tool (PEDT) data were collected at the same time. All subjects with LPE and healthy controls were genotyped for polymorphisms in the TPH2 gene. Allele and genotype frequencies of single-nucleotide polymorphisms (SNPs) were compared between the patients and controls. Main Outcome Measure The main outcome measures are IELT and PEDT to diagnose LPE. The association of LPE with TPH2 gene polymorphisms in these areas was investigated. Results The IELT, PEDT scores, and education levels in the LPE group were significantly different from those in the control group. Statistically significant differences were found in the SNPs of SNV019 and rs4290270. The frequencies of the G allele and G/A genotype of SNV019 were significantly higher in the patients with LPE than in the controls (P = .045 and .037, respectively). The A allele and A/A genotype of rs4290270 were more frequent in the patients with LPE than in the controls (P = .037 and .049, respectively). In the dominant model of inheritance, the SNV019 polymorphism in the patients with LPE was significantly different from that in the controls (odds ratio [95% confidence interval] = 2.936 [1.066–8.084], P = .037). In men with LPE, there was no statistically significant association between genotype and median IELT. Conclusion The SNPs SNV019 and rs4290270 of the TPH2 gene seemed to be associated with LPE in the Han population. Men with the A allele of SNV019 or the T allele of rs4290270 may be less likely to suffer from LPE.

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.

Background: Premature ejaculation (PME) can be defined as a lack in the normal voluntary control over ejaculation. It is the most common sexual dysfunction encountered by the male populace. In general, these patients presents with distress. Hence, a novel treatment to eliminate their problem is required. Although the role of SSRI has already been established, the high discontinuation rate and other types of sexual dysfunctions associated with SSRIs reduce their efficacy in controlling this menace. Levosulpiride is a new drug indicated in treatment of PE. Aims and Objectives: The objective is to study the efficacy of levosulpiride; paroxetine and their comparison in patients of PE. Methodology: Index of premature ejaculation (IPE) and intravaginal ejaculation latency time (IELT) were used. A total of 36 patients (18 in each group) were included. The patients were assessed at baseline; at 4 weeks’ and at 8 weeks’ interval. Results: On comparison the score of IPE in domains of ejaculation control, sexual satisfaction, and the total score of IPE were statistically significant on all the three visits. However, the distress score of IPE and the IELT score were statistically not significant between the two groups. Conclusion: No doubt both agents are efficacious in patients of PME but paroxetine is more efficacious than levosulpiride. At the same time, levosulpiride is a lesser studied and used drug hence more research should be done for it.

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.

Introduction Premature ejaculation (PE) is a significant problem as it can cause a loss of sexual self-confidence and a significant deterioration in quality of life. The frequency of PE varies between 9% and 27%. In the current study, we aimed to compare the levels of the serotonin metabolite 5HIAA (5 hydroxyindole acetic acid) in the cerebrospinal fluid (CSF) of patients with and without PE according to IELT (intravaginal ejaculation latency time) in order to investigate the relationship of PE with CSF 5HIAA levels. Materials and methods A total of 60 male patients were included in the study who were planning to undergo surgery under spinal anesthesia, 30 in the patient (PE) group (all of the included patients had an IELT of 1 min). Levels of CSF 5HIAA were measured. Results There was a significant negative correlation between IELT and the 5HIAA variables in all patients (r = −0.322, p = 0.012). Although the average 5HIAA levels (nmol/L) were higher in the patient group (86.80 ± 28.33) than in the control group (76.44 ± 35.91), this difference was not significant (p = 0.22). Discussion Results of the current study bring new and different perspectives to the explanation of PE pathophysiology. There is a need for more specific and genetic studies to determine the best treatment for this common disorder.

Introduction Besides erectile dysfunction, premature ejaculation (PE) is the most frequent male sexual disorder and shows a high level of bother and distress. The negative consequences of long-term and unsuccessfully treated PE on both patient and partner are well established in the literature and include personal distress, impairment of the partner’s sexual function, and interpersonal difficulties. Aim To outline the consequences of untreated PE and the advantages and disadvantages of currently available treatment options with a special focus on a new topical eutectic lidocaine/prilocaine metered dose spray (Fortacin; Lidocaine/Prilocaine, Recordati, Milan, Italy) which represents the second officially approved drug in this indication. Methods Narrative overview of the literature synthesizing the findings of literature retrieved from searches of computerized databases such as Web of Science, Medline, PubMed, and Google Scholar, hand searches, and authoritative texts. Combinations of keywords including premature ejaculation, ejaculatory control, intravaginal ejaculation latency time, IELT, PE, PDE5 inhibitors (PDE5i), SSRIs, topical anesthetics, lidocaine, prilocaine, and treatment were used. In the end, 59 studies published between 2000 and 2018 were considered relevant for this review. Main Outcome Measures Published studies on PE-related negative psychosocial outcomes, as well as advantages and disadvantages of currently available off-label and officially approved treatment options. Results Although a variety of treatment options for PE have shown marked improvements in stopwatch-measured intravaginal ejaculation latency time (IELT) and patient-reported outcomes as assessed by the Premature Ejaculation Profile (PEP), none of the investigated drugs has reached market approval. The only so far officially approved medication—dapoxetine—is characterized by high discontinuation rates of up to 90%, mostly because of high side effects, cost issues, efficacy below expectations, and the need for scheduling sexual intercourse. Conclusion With the official approval in Europe the new dose-metered lidocaine-prilocaine spray (Fortacin) may become a real first-line therapy option for PE and may offer a satisfactory and affordable solution, especially because of its unique galenic preparation, making its handling easy and customer friendly. In addition, it has the potential to significantly increase the currently low patients’ acceptance of available monotherapies and become an established second-line therapy for the severe PE patients with IELTs Porst H, Burri A. Novel treatment for premature ejaculation in the light of currently used therapies: A review. Sex Med Rev 2019; 7:129–140.

Clinical characteristics of 216 adult males previously diagnosed with premature ejaculation (PE) were studied. Using a survey questionnaire, characteristics included intravaginal ejaculation latency time (IELT), penile hardness scores and the refractory period (RP). Ninety-four PE patients reported they had experienced vaginal intercourse more than once (2 to 4 times) in one day (~44%). IELT was significantly increased at the second and subsequent intercourses, and IIEF-15 (International Index of Erectile Function-15) and relevant subclass scores were markedly improved compared to their first intercourse and also compared to the single intercourse group in this cohort study. Overall sexual satisfaction was achieved in the PE patients with multiple intercourse experiences. The same trend was observed in both the patients diagnosed with lifelong and acquired PE. Based on the evidence, the argument is that the PE patients who were diagnosed using their performance at the first intercourse but who have the ability to participate in multiple vaginal intercourses in one day are unlikely to be true PE. The false PE may account for over 40% of PE patients diagnosed by current guidelines and definitions.

Introduction and objective: The purpose of this study was to compare the severity of lower urinary tract symptoms (LUTS) between patients with and without premature ejaculation (PE). Materials and method: The relationship between the severity of LUTS and PE was investigated among 825 male subjects, who underwent medical check-up between July 2013 and July 2018 in our hospital. PE was defined by self-reported intravaginal ejaculation latency time (IELT). The severity of LUTS was determined by international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), transrectal ultrasonography (TRUS), and uroflow rate. A total of 825 subjects were classified into three groups: PE-group (N = 60), Self-reported PE-group (N = 353), and Non-PE group (N = 412). Results: In comparison analysis involving the two groups, the PE-group and the Self-reported PE-group were analyzed to be statistically significantly higher in IPSS items and OABSS items, compared to the Non-PE group (P < 0.05). This showed the same results in the univariate analysis (P < 0.05). Multivariate analysis conducted with the PE-group versus the Non-PE group, and the Self-reported PE-group versus the Non-PE group, revealed significant differences in the values of total IPSS (P < 0.05). Conclusion: Comparison between the PE-group, which included the Self-reported PE-group, and the Non-PE group suggest that the severity of LUTS was comparatively higher in the PE-group. Thus, it is thought that being associated with or without PE may be a significant factor to consider, which affects LUTS severity.

To analyze the abnormal amygdala structure and function in lifelong premature ejaculation (PE) patients compared with healthy controls (HCs). Forty-four lifelong PE patients and thirty-one HCs were enrolled in this study. Each subject was diagnosed with PE using a Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculation latency time (IELT) score. Based on t-tests and Pearson correlation analysis, the voxel-based morphometry and functional connectivity (FC) analyses were applied to evaluate brain structural and functional changes by using T1-weighted and resting-state functional magnetic resonance imaging scans. Lifelong PE patients had decreased gray matter volume in the bilateral amygdala and increased FC between the amygdala and precuneus, posterior cingulate cortex (PCC), and middle temporal cortex (MTC), as well as decreased FC between the amygdala and precentral gyrus, insula, and inferior frontal gyrus. Moreover, significantly negative correlations between the IELT score and the mean z-score from amygdala-MTC (r = −0.49) and amygdala-PCC (r = −0.48) FC were found in lifelong PE patients. Our study investigated the abnormal amygdala-related structure and connectivity patterns in PE patients, which might provide novel perspective for understanding the crucial role of the amygdala in the neural mechanism of PE. • As one of the most common diseases in men, PE may be related to abnormal brain mechanisms. • Functional and structural magnetic resonance imaging used to explore amygdala abnormalities in PE patients. • The correlation between clinical scores and functional connectivity was used to assess the reasonability of the results.

There is a lack of objective tools to comprehensively evaluate premature ejaculation (PE) treatment results clinically. We aimed to describe the development of a novel scoring system for PE treatment results as an example of using the Delphi method and an analytical hierarchy process for complex decision-making in the field of sexual medicine. A Delphi question survey was adopted to collect expert opinions from 47 Chinese specialists in andrology/urology on the assessment of PE treatment outcomes based on four primary properties, that is, the improvement in intravaginal ejaculation latency time, a couple’s mental status, the ability to control ejaculation, and sexual intercourse satisfaction. Different weights on those primary properties were assigned to create a mathematical hierarchy matrix and then perform an analysis. The scores were assigned according to the calculated weights. The ratio among the combined weights of the four primary properties was 1:3:2:3. The total numerical score was 36. Scores above 27, between 26 and 18, and below 17 indicated significant improvement, moderate improvement, and no improvement in PE, respectively, with selected treatments. The scoring system with 36 points can be used by physicians, patients, and their sexual partners to comprehensively and objectively assess quantitative PE treatment results.

Premature ejaculation (PE) is a multifactorial problem with a complicated aetiology that has detrimental effects on female partners' sexual function. However, there is a lack of studies on the relationship between the factors related to PE and female sexual dysfunction (FSD) in China. We aimed to identify and explore the relationship between the factors associated with PE and FSD.Ultimately, information was collected from 761 couples: 445 couples with PE complaints and 316 couples without PE complaints. The mean ages of the men with and without PE complaints were 36.29 ± 9.87 years and 31.48 ± 10.77 years, respectively. Female partners in the group with PE complaints reported lower total and subdomain female sexual function index (FSFI) scores, and approximately 65% of them were diagnosed with FSD (vs.31.96%). A PE duration of more than 14 months, a self-estimated intravaginal ejaculation latency time (self-estimated IELT) less than 2 min, a negative attitude towards PE problems, men's introversion, and men's depression were risk factors for FSD in the PE group.PE affects not only the patient himself but also the spouse. Comprehensive analysis reveals a clear relationship and interaction between female sexual function and PE. Moreover, in PE treatment, we should not ignore the occurrence of FSD and its impact and should emphasize the treatment of couples together.RéSUMé: CONTEXTE: L’éjaculation précoce (EP) est. un problème multifactoriel, avec une étiologie compliquée, qui a des effets néfastes sur la fonction sexuelle des partenaires féminines. Cependant, il existe un manque d’études en Chine portant sur la relation entre les facteurs liés à l’EP et la dysfonction sexuelle féminine (DSF). Nos objectifs étaient d’identifier et d’explorer la relation entre les facteurs associés à l’EP et la DSF. RéSULTATS: Finalement, des informations ont été recueillies auprès de 761 couples: 445 couples avec plaintes d’EP et 316 couples sans plaintes d’EP. L’âge moyen des hommes avec et sans plaintes d’EP était respectivement de 36,29 ± 9,87 ans et 31,48 ± 10,77 ans. Les partenaires féminines du groupe avec plaintes d’EP ont obtenu des valeurs abaissées des scores, totaux et par sous-domaines, de l’indice de la fonction sexuelle féminine (IFSF), et environ 65% d’entre elles ont eu un diagnostic de DSF (pour 31,96% dans le groupe témoin). Une durée d’EP de plus de 14 mois, un temps intravaginal auto-estimé de latence d’éjaculation (IELT auto-estimé) de moins de 2 min, une attitude négative envers des problèmes d’EP, une introversion des hommes, et une dépression chez les hommes étaient des facteurs de risque de la DSF dans le groupe avec EP. CONCLUSIONS: L’EP affecte non seulement le patient lui-même, mais aussi la conjointe. L’analyse complète révèle une relation et une interaction claires entre la fonction sexuelle féminine et l’EP. En outre, dans le traitement de l’EP, nous ne devrions pas ignorer l’apparition de la DSF et son impact, et nous devrions mettre l’accent sur le traitement du couple.

The aim of our study was to compare melatonin levels of patients with lifelong premature ejaculation (LPE) (n:60) with healthy controls (n:30) and to investigate the changes of melatonin levels in the treatment with dapoxetine and sertraline. Age, body mass index, duration of marriage, weekly intercourse number, International Index of Erectile Function scores, Intravaginal Ejaculation Latency Time (IELT) and melatonin levels were recorded. LPE patients were divided into two treatment groups. The first group was included 30 patients, who received 60 mg dapoxetine for six weeks, twice a week, an hour before intercourse. The second group received 50 mg of sertraline daily, for six weeks. IELT and melatonin measures were repeated after the treatment. IELT (dapoxetine group: 41.22 ± 21.3 s, sertraline group: 48 ± 23.11 s, control group: 195.54 ± 84.14 s; p < .001) and melatonin levels (dapoxetine group: 5.75 ± 2.04 pg/mL, sertraline group: 5.49 ± 2.88 pg/mL, control group: 13.4 ± 12.09 pg/mL; p < .001) of both LPE groups were significantly lower than control group. Following the six-week sertraline (before: 48 ± 23.11 s, after: 101.01 ± 59.55 s; p < .001) and dapoxetine (before: 41.22 ± 21.3 s, after: 97.39 ± 44.1 s; p < .001) treatments, IELT increased. The melatonin levels increased in the sertraline group (before: 5.49 ± 2.88 pg/mL, after: 10.6 ± 7.37 pg/mL; p < .001). Our results indicate that melatonin levels of LPE patients are lower than levels of healthy volunteers. Furthermore, we found a significant increase in melatonin levels following sertraline treatment.

To evaluate the safety and efficacy of Chinese medicine, Qiaoshao formula combined with dapoxetine was used for the treatment of premature ejaculation in a real-life setting. Nine hundred and five males diagnosed with premature ejaculation were reviewed in this retrospective cohort study. We divided the patients into two groups: dapoxetine alone and Qiaoshao formula combined with dapoxetine according to actual interventions provided to patients in clinics. The perceived intravaginal ejaculation latency time and the premature ejaculation profile measures markedly improved in both groups. However, in men with severe premature ejaculation (baseline perceived intravaginal ejaculation latency time

Introduction: Premature ejaculation (PE) is the most common type of sexual disorder among men which comprises a great of problems. Varicocele is defined as the dilation of the pampiniform venous plexus draining the testicle. At present, selective serotonin reuptake inhibitors antidepressants, topical anesthetics, tramadol, phosphodiesterase type 5 inhibitors are the common alternative strategy to improve PE. However, these therapeutic measures have several shortcomings and side effects. Recently, the correlation between varicocele and PE has attracted the attention of some researchers. A few studies consider microsurgical varicocelectomy can be a new remedy for PE. But it is still absent enough a great deal of convincing evidence. The study will assess the effectiveness and safety of the microsurgical varicocelectomy treatment in PE patients. Methods and analysis: Electronic databases including English databases (PubMed, MEDLINE, EMBASE, Web of Science, Cochrane Library) and Chinese databases (China National Knowledge Infrastructure, China Biology Medicine Database, Wanfang Database, VIP Database) will be searched from their inception to December 2020 to recognize related studies. All the randomized controlled trials of microsurgical varicocelectomy for the management of PE patients will be included. The potential outcome will include intravaginal ejaculation latency time, Chinese index of sexual function for premature ejaculation-5, visual analogue score, premature ejaculation diagnostic tool, success treatment rate, serum testosterone levels. We will conduct this study strictly according to the Cochrane Handbook for systematic reviews of interventions. Results: The current study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings in the February 28, 2021. Conclusion: This systematic review will provide more evidence to assess whether microsurgical varicocelectomy is an effective intervention for patients with PE. The results will be published in a public issue journal and offer the urologists and andrologists help to make clinical decisions. Ethics and dissemination: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published studies, and since there are no patients involved in this study, individual privacy will not be under concerns. The results of this review will be disseminated to peer-reviewed journals or submit to related conferences. Protocol registration number: INPLASY202060058

INTRODUCTION AND OBJECTIVE:Delayed ejaculation (DE), defined as a delay in intravaginal ejaculation latency time, is an understudied conditioned with an estimated prevalence of 5%. However, literat...

Background and objective Although several studies have reported that sexual dysfunction is associated with chronic prostatitis (CP), specific differences in self-reported questionnaires and correlation with CP are not well-known. This study aimed to evaluate the prevalence and correlation of sexual dysfunction in men with CP. Material and methods This cross-sectional study included 892 men who visited our health care center, who were then divided into two groups. In Group 1, subjects are characterized with National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) pain score ≥4, and Group 2 subjects are characterized with NIH-CPSI

Premature ejaculation is a common male sexual disease in andrology practice. The goal of essay is to investigate the relation of anogenital distance that predicts prenatal testosterone exposure with premature ejaculation. Between January and May 2019, 150 men were participated in the study. The patients were evaluated with anamnesis and physical examination; age, smoking, alcohol consumption, intravaginal ejaculation latency time, body mass index, premature ejaculation diagnostic tool, distance from anal point to scrotum and distance from anal point to penis were recorded. According to premature ejaculation diagnostic tool score, the patients were classified as premature ejaculation group (score ≥11) and control group (score

Background The treatment effect of dapoxetine in real-world practice is not well established. This study was to investigate the factors influencing efficacy of dapoxetine for the treatment of Premature ejaculation (PE) in the real-world setting. Methods Altogether 154 patients were followed up between Jan 2015 and Dec 2015. The clinical global impression of change (CGIC), premature ejaculation profile (PEP), the estimated intravaginal ejaculation latency time (eIELT) and estimated number of intravaginal thrusts before ejaculation (NITBE) were collected. The clinical characteristics of patients with CGIC = 0 and CGIC≥1 were compared. Results After 4 weeks treatment, an obvious improvement compared with the baseline was found regarding mean eIELT (2.4 ± 1.6 min vs 1.0 ± 0.7 min, P P P = 0.010) and PEDT (P = 0.009) score at baseline. The adverse effects were acceptable. Conclusion Dapoxetine was well-tolerated and improved the sexual satisfaction of patients with PE. The severity of PE based on PEDT and NITBE suggest that there could be an effectiveness change with dapoxetine use in real-world practice.

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.

Penile hypersensitivity plays an important role in premature ejaculation (PE), but differences in penile sensitivity among subtypes of PE are unknown. Therefore, we compared penile sensory thresholds in PE subtypes of lifelong and acquired PE, PE with and without erectile dysfunction (ED), PE with an intravaginal ejaculation latency time ≤1 min and >1 min, and PE with and without orgasmic pleasure perceptual dysfunction. During August 2014 to January 2016, 136 patients with PE were included. Penile warm, cold, and vibratory thresholds were measured. Data of clinical characteristics, sexual life, Premature Ejaculation Diagnostic Tool (PEDT) score, and the 5-item version of the International Index of Erectile Function (IIEF-5) score were collected. Vibratory thresholds of the PE with ED group were higher in the right coronal sulcus (median amplitude: 4.92 vs 3.65 μ m, P = 0.02) and the right penile shaft (median amplitude: 3.87 vs 3.30 μ m, P = 0.03), while differences in penile sensory thresholds between other subtypes were not significant. The median PEDT score was lower in the PE without ED group (12 vs 14, P < 0.001). The IIEF-5 and PEDT scores were negatively correlated (r = −0.29, P < 0.001). Patients with orgasmic pleasure perceptual dysfunction had a lower median IIEF-5 score (20 vs 21, P = 0.02). Patients with PE and ED had lower penile sensitivity, and ED was associated with more severe symptoms and weaker orgasmic pleasure perception. In men with PE, management of comorbid ED is necessary. In case of side effects in erectile function, topical anesthetics should be cautiously used in men with PE and ED.

To clarify the efficacy of phosphodiesterase-5 inhibitors (PDE5Is) and selective serotonin reuptake inhibitors (SSRIs) in men with premature ejaculation (PE). We searched the PubMed, Embase, and Cochrane Library databases to identify all randomized, controlled trials (RCTs) and compared the results, including intravaginal ejaculation latency time, satisfaction, intercourse per-week and side effects after treatment with PDE5I or SSRIs versus placebo, combined use of PDE5I with SSRIs versus PDE5I or SSRIs alone, and PDE5I versus SSRIs for treating PE. The study inclusion criteria were met by 23 studies (ten RCTs with five crossover studies) involving 6145 patients. The data synthesized from these studies indicated that the efficacy of PDE5Is and SSRIs was better than that of placebo (p

There are very few studies that have evaluated premature ejaculation characteristics in regard to subtypes. Additionally, to our knowledge, there are no studies which have explored testosterone replacement therapy in secondary premature ejaculation patients with testosterone deficiency. Therefore, our aims were as follows: (a) to determine the characteristics of patients with premature ejaculation in regard to the four subtypes of premature ejaculation and (b) to determine the efficacy of testosterone replacement therapy in the treatment of testosterone-deficient patients with secondary premature ejaculation. Patients who applied to our clinic from May 2010 to August 2018 with premature ejaculation were included in this study. The mean age of the study group was 36.42 (min-max: 24-52) years. Those with secondary premature ejaculation were found to have significantly lower testosterone concentration compared to the other groups. Shortest mean intravaginal ejaculation latency time and lowest International Index of Erectile Function-5 score were found among those with secondary PE. In regard to treatment results, recipients of testosterone replacement demonstrated a 4.8-fold increase in mean intravaginal ejaculation latency time, while dapoxetine recipients had a 1.8-fold increase. Our findings demonstrate that testosterone replacement may be a promising treatment for those with secondary PE in the presence of testosterone deficiency.

Purpose: To investigate the association of erectile dysfunction (ED), premature ejaculation (PE), and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men with late-onset hypogonadism (LOH). Materials and Methods: We reviewed the data of 408 enrolled men between January 2014 and January 2019. All participants completed the Androgen Deficiency in the Aging Male (ADAM), international index of erectile function-5 (IIEF-5), National Institutes of Health chronic prostatitis symptom index (NIH-CPSI), and premature ejaculation diagnostic tool (PEDT) questionnaires. Participants were divided by ADAM positive (ADAM+: Group 1) and ADAM negative (ADAM–: Group 2). Results: Total of 289 subjects were in Group 1 and 119 were in Group 2. The mean age was 53.8±7.8 years. The mean total testosterone was 4.8±1.2 ng/dL and showed no differences between the groups (p=0.839). In Groups 1 and 2, ED (IIEF≤21) was identified in 233 (80.6%) versus 37 (31.1%), respectively (p

To evaluate the efficacy and safety of tamsulosin combined with dapoxetine in the treatment of type IIIB chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) that is complicated by premature ejaculation (PE), a total of 251 CP/CPPS patients with PE were recruited from nine hospitals across China and were randomly divided into two groups: one received tamsulosin as a control, and the other received a combination therapy of tamsulosin and dapoxetine. Follow-up was conducted at four time points, and indicators describing CP/CPPS and PE were compared between the two groups. In all, 223 patients were followed up at least once, and 114 patients completed all of the treatment process. The combination group showed more improvement in the symptoms of both PE and CP/CPPS, including thrust number (50.5 vs. 45), premature ejaculation profile score (11.39 vs. 6.96), intravaginal ejaculation latency time (5.95 min vs. 2.63 min) and the National Institutes of Health Chronic Prostatitis Symptom Index (7.44 vs. 11.81) in comparison with the tamsulosin group. In conclusion, for CP/CPPS patients with PE, tamsulosin combined with dapoxetine provided better therapeutic efficacy in the treatment of not only PE symptoms but also CP/CPPS indicators in comparison with tamsulosin monotherapy.

Although premature ejaculation (PE) is a common male sexual dysfunction, its pathophysiology has not been fully elucidated. Several medical problems such as erectile dysfunction, depression, anxiety, hormonal disorders and chronic prostatitis may play a role in the etiology of acquired PE. This study aims to evaluate the frequency of these etiologic factors among patients with acquired PE. Between May and July 2016, 53 men with acquired PE were included in the study. Self-estimated intravaginal ejaculation latency time (IELT) of these patients was recorded along with their medical history and physical examination findings. Moreover, 5-item version of the International Index of Erectile Function (IIEF-5), premature ejaculation profile (PEP), anxiety and depression scales (STAI-1, STAI-2, and BECK), and chronic prostatitis symptom index (NIH-CPSI) were administered. Fasting plasma glucose, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, total and free testosterone, total prostate specific antigen, thyroid and thyroid stimulating hormone levels were measured. Urine analysis and 2 cup tests were also studied. Mean age of the patients was 42.41 ± 11.14 (22–60). Mean duration of the PE complaint was 34.18 ± 36.76 (3–144) months. Mean IELT time of the patients was 38.28 ± 30.79 (3–180) s. Of the patients; 69.81%, 62.26%, 56.60%, 45.28%, 30.19%, 24.53%, 16.98%, 15.09%, and 7.55% had depression, chronic prostatitis, erectile dysfunction, anxiety, diabetes mellitus, abnormal FSH or LH, hypoprolactinemia, hyperthyroidism, and high testosterone levels, respectively. The results of our study revealed that anxiety disorders, depression, erectile dysfunction, and chronic prostatitis are common among patients with acquired PE and may play role in the etiology of this problem. There is a need for further researches related to the exact pathophysiology of acquired PE with larger number of patients.

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.

BACKGROUND The STin2 VNTR polymorphism has a variable number of tandem repeats in intron 2 of the serotonin transporter gene. We aimed to explore the relationship between STin2 VNTR polymorphism and lifelong premature ejaculation (LPE). MATERIAL AND METHODS We recruited a total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as LPE, and 101 controls without PE complaint. Allelic variations of STin2 VNTR were genotyped using PCR-based technology. We evaluated the associations between STin2 VNTR allelic and genotypic frequencies and LPE, as well as the intravaginal ejaculation latency time (IELT) of different STin2 VNTR genotypes among LPE patients. RESULTS The patients and controls did not differ significantly in terms of any characteristic except age. A significantly higher frequency of STin2.12/12 genotype was found among LPE patients versus controls (P=0.026). Frequency of patients carrying at least 1 copy of the 10-repeat allele was significantly lower compared to the control group (28.3% vs. 41.8%, OR=0.55; 95%CI=0.31-0.97, P=0.040). In the LPE group, the mean IELT showed significant difference in STin2.12/12 genotype when compared to those with STin2.12/10 and STin2.10/10 genotypes. The mean IELT in10-repeat allele carriers was 50% longer compared to homozygous carriers of the STin2.12 allele. CONCLUSIONS Our results indicate the presence of STin2.10 allele is a protective factor for LPE. Men carrying the higher expression genotype STin2. 12/12 have shorter IELT than 10-repeat allele carriers.

Background: Dopamine and serotonin transporter genes play an important role in the control of the mechanism of ejaculation. Objectives: Evaluation of the role of serotonin transporter gene promoter and dopamine transporter gene polymorphisms in lifelong premature ejaculation and their role in determining the response to paroxetin and escitalopram. Patients and Methods: Eighty consecutive patients and controls were recruited. Forty of them suffered lifelong premature ejaculation. They were divided into two equal groups: One group received paroxetine (20 mg daily)for 1 month, and the other one received ecistalopram (20 mg daily) for 1 month. Their wives were instructed to measure the intravaginal ejaculation latency time using stopwatch. Five ml blood was withdrawn from patients and controls for PCR. Results: The present study revealed that the majority of the patients were SL and SS genotypes of the serotonin transporter gene promoter polymorphism. Also, this study revealed that the majority of the patients were (10R/10R) genotypes of the dopamine transporter gene polymorphism. Both of paroxitine and escitalopram significantly delayed ejaculation in the responders. Conclusion: The study revealed significant association between such response and dopamine transporter gene polymorphism. The present study augmented the significant effect of both paroxetine and escitalopram in delaying ejaculation in the responders.

The therapeutic armamentarium currently available for the treatment of premature ejaculation (PE) is not highly satisfactory. However, phytotherapeutics appear to be an interesting option for PE management. The present study aimed to evaluate the tolerability and efficacy of a phytotherapeutic combination of Rhodiola rosea, folic acid, biotin and zinc (EndEP®) in the treatment of patients affected by lifelong PE. All patients affected by lifelong PE who were attending three Urological Institutions from July to December 2014 were enrolled in this prospective, multicentre, phase I–II study. All patients were assigned to receive oral tablets of EndEP® (one tablet per day) for 90 days. Clinical and instrumental analyses were carried out at enrolment and at the end of the study. International Prostatic Symptom Score (IPSS), International Index of Erectile Function (IIEF)-15, Premature Ejaculation Diagnostic Tool (PEDT) and Short Form (SF)-36 questionnaires were used. The intravaginal ejaculation latency time (IELT) for each event was also evaluated using the stop-watch technique. The main outcome measure was the difference from baseline in PEDT questionnaire and mean IELT at the end of the follow-up period. In total, 91 patients (mean age, 32.3±5.6 years) were analysed. The baseline questionnaires mean scores were 1.1±1.6, 26.1±2.9, 15.3±3.4 and 98.2±0.5, for IPSS, IIEF-15, PEDT and SF-36, respectively. The mean IELT at baseline was 73.6±46.9s. At the follow-up examination (90 days after the start of treatment), no statistically significant differences were identified in terms of IPSS (1.4±1.5) or IIEF-15 (26.3±3.1) compared with the pre-treatment values (P=0.19 and P=0.64, respectively). A statistically significant difference was detected between the mean IELT at enrolment and after treatment (73.6±46.9 vs. 102.3±60.0; P

BACKGROUND This study aimed to explore the relationship between premature ejaculation (PE) and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with respect to the biallelic and triallelic classifications. MATERIAL AND METHODS A total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as having lifelong premature ejaculation (LPE) and 101 controls without PE complaint were recruited. All subjects completed a detailed questionnaire and were genotyped for 5-HTTLPR polymorphism using PCR-based technology. We evaluated the associations between 5-HTTLPR allelic and genotypic frequencies and their association with LPE, as well as the intravaginal ejaculation latency time (IELT) of different 5-HTTLPR genotypes among LPE patients. RESULTS The patients and controls did not differ significantly in terms of any characteristic except age. The results showed no significant difference regarding biallelic 5-HTTLPR. According to the triallelic classification, no significant difference was found when comparing the genotypic distribution (P=0.091). However, the distribution of the S, LG, and LA alleles in the cases was significantly different from the controls (P=0.018). We found a significantly lower frequency of LA allele and higher frequency of LG allele in patients. Based on another classification by expression, we found a significantly lower frequency of the L'L' genotype (OR=0.37; 95%CI=0.15-0.91, P=0.025) in patients with LPE. No significant association was detected between IELT of LPE and different genotypes. CONCLUSIONS Contrary to the general classification based on S/L alleles, triallelic 5-HTTLPR was associated with LPE. Triallelic 5-HTTLPR may be a promising field for genetic research in PE to avoid false-negative results in future studies.

In the present issue of Investigative and Clinical Urology, Janssen and Waldinger [1] publish an important mathematical contribution on the intravaginal ejaculatory latency time (IELT) distributions of men in the general adult population compared to the IELT distribution of men with lifelong premature ejaculation (PE). Data used to study these distributions were derived from earlier studies on Caucasian males in Europe and North America. Although both populations (normal and lifelong PE) are small due to the experimental design with stopwatch methodology, the authors have convincing and valid arguments that both populations have distinct mathematical IELT distributions. This leads to interesting consequences, hypotheses and research possibilities. Lifelong PE has convincingly been shown to be a very stable putative endophenotype within the range of all IELT's measured all over the world in different populations and cultures [2]. This stability strongly suggests that this endophenotype is caused by underlying biological mechanisms, presumably anchored in the central nervous system. The mathematical different distribution models of the IELT in the general population and lifelong PE males furthermore strongly supports biological differences underlying these IELT distributions and argues against psychological or behavioral interventions aimed at elongation of the IELTs in PE males. Whether such biological and fundamental different processes in the IELT of lifelong PE can be considered as 'pathological' remains a tricky question. As long as men present their PE as an unwished phenomenon from which they and their partner suffer and look for help, PE can be considered as pathological and deserves treatment if possible. Further studies into the underlying mechanisms of life long PE is urgently needed as the only efficient treatment of PE so far are the SSRI. Apart from their side effects, SSRIs have to be taken daily and life long, i.e., as long as a wish for a 'normal' sex life exists. Ideally, an 'on demand' treatment should be used, but the existing SSRI's, including dapoxetine as an approved 'on-demand' prescription drug for PE, hardly fulfill such claims [3]. Much more fundamental insight into the brain and spinal cord mechanisms involved in sexual behavior and ejaculatory processes are needed to possibly develop new pharmacological approaches to better treatment of lifelong PE. Several strategies have to be developed and applied, in particular genetic, genomic and epigenetic approaches and techniques have to be implemented. The biological hardware differences in IELT between the normal and abnormal (lifelong PE) populations and the high familiar occurrence of PE [4] suggest that genetic technology (e.g., GWAS and expression studies) might help to identify factors (e.g., functional SNPs) that are involved. Moreover, central nervous system (CNS) functional magnetic resonance imaging studies (including spinal cord imaging) comparing normal IELT with lifelong PE men, where males are challenged with various sexual stimuli (visual, tactile) might unravel or differentiate activity (or lack of) in brain/spinal cord areas that generate new ideas and hypotheses on brain mechanisms involved. Similarly, comparison of SSRI-treated (by preference chronically treated) males with normal IELT and lifelong PE males using brain/spinal cord imaging might further contribute to understanding of the mechanisms and brain localizations of the SSRI-induced changes in focal areas. Fundamental results from such brain studies in untreated and SSRI-treated populations might also generate hypotheses that can be used in a translational way in animal models of sexual behavior and sexual dysfunctions. The serotonergic (5-HT) system seems an extremely important neurotransmitter system in the modulation of sexual behavior including ejaculatory processes [5]. Most research into this topic derives from animal studies, but the translational prediction of rat models of ejaculatory speed for human ejaculation latencies (IELT) appears rather high [6]. In general, increased 5-HT levels in the CNS elevate ejaculatory thresholds probably via activation of 5-HT1B and 5-HT2C receptors, whereas 5-HT depletion decreases the ejaculatory threshold. 5-HT1A receptor activation strongly facilitates ejaculatory processes, either mediated by lowering 5-HT levels via activation of presynaptic (somatodendritic) 5-HT1A autoreceptors and/or stimulation of postsynaptic 5-HT1A heteroreceptors. We found that concurrent treatment of SSRIs and a silent 5-HT1A receptor antagonist, strongly facilitated the inhibiting effects of SSRIs on male ejaculation [6], both after acute and chronic dosing. This suggests a new approach to an 'on-demand' treatment of PE; acute SSRI administration (e.g., paroxetine or escitalopram) plus a 5-HT1A receptor antagonist (e.g., pindolol, a relative weak 5-HT1A receptor antagonist and a β-adrenoceptor antagonist-with the intrinsic risk of cardiovascular side effects). Safarinejad [7] used a high dose of pindolol (7.5 mg/d) for 6 weeks to men with PE who were refractory to paroxetine (20 mg/d) treatment for at least 2 months. Pindolol had a slight facilitating effect on PE in these paroxetinetreated men over the 6 weeks treatment. Although in this case pindolol appears a mild augmentation strategy in paroxetine-refractory patients, the data suggest that pindolol exerts its effects via blockade of 5-HT1A receptors interfering with the SSRI-induced enhancement of overall 5-HT neurotransmission. Further support for an important role of the 5-HT1A receptor in the inhibitory action of SSRIs on sexual behavior and ejaculation, in depression treatment considered as unwanted side effect, comes from findings with vilazodone in sexual behavior. Vilazodone exerts blockade of the serotonin transporter (SERT) concomitant with 5-HT1A receptor agonistic activity. In a rat model of measuring sexual side effects, vilazodone has no inhibitory effects on male sexual behaviors after acute or chronic treatment, whereas paroxetine or citalopram, SSRI, had strong inhibitory effects [8]. This suggests that vilazodone is probably not very (or not at all) effective in lifelong PE, but a potential attractive antidepressant/anxiolytic with no or less sexual side effects. The serotonergic system in the brain is a complex, extremely ramified system emerging in the raphe nuclei in the midbrain and projecting to practically all areas of the brain and spinal cord [3]. The 5-HT complex (in)directly interacts with all neurotransmitter systems in the CNS via 14 different postsynaptic (hetero) receptors and presynaptic autoreceptors; the serotonin transporter (SERT or 5-HTT) is the main regulatory mechanism in the modulation of the serotonergic tone via uptake of released 5-HT, thereby terminating 5-HT-ergic stimulation [3]. The SERT is the target of SSRI's that are known to delay ejaculation. Having a high affinity for 5-HT, the SERT controls the duration, availability and signaling capacity of synaptic 5-HT and therefore might determine the speed of ejaculation. If SERT activity is high, serotonergic neurotransmission is low(er) and this seems associated with a short IELT (5-HT functions as a brake on ejaculation). The 5-HTT functioning is moderated by a polymorphism in the 5-HTT promoter region of the SERT gene (SCL6A4) which encodes for the SERT protein (5-HT transporter-linked promoter region: 5-HTTLPR). The latter has a short (S) and a long (L) variant allele associated with low (S) and high (L) transcriptional activity. Thus, SS genotypes have much lower SERT activity than LL genotypes (SL are intermediate) and it has been postulated that men with SS genotype have longer IELT durations than men with LL genotypes. This was confirmed in a population of men with life long PE [9]. This is indeed a remarkable finding because in a population with already extremely short ejaculation latencies, a functional polymorphism (LL) was associated with a reduction of IELT of 50%. Data in the normal population are lacking, but a comparable pattern might be expected. An important remark, however, is that the promoter length polymorphism in the SERT gene cannot be the genetic base for lifelong PE but only a modulatory factor [9]. Moreover, the ejaculatory process itself is not critically dependent on the serotonergic system; it seems logical to postulate that many other neurotransmitter systems in the CNS contribute to the complex ejaculatory process although much research is needed to unravel the complex processes involved [3]. In conclusion: the finding by Janssen and Waldinger [1] that the ejaculatory process in lifelong PE essentially differs from that in normal ejaculating males, strongly indicates that PE can be considered as a dysfunction of the ejaculatory process. Future studies have to support this finding and might lead to new ideas about PE and possibly new treatments.

Introduction: Premature ejaculation (PE) affects 8% to 30% of adult men worldwide. Recently, the incidence of PE is on the rise. A series of prior studies suggested that the incidence of PE is related to various biological factors as low testosterone, low serum vitamin D, diabetes, lower urinary tract symptoms, and other psychological factors. At present, the major treatments include selective serotonin reuptake inhibitors antidepressants (dapoxetine, paroxetine), topical anesthetics, phosphodiesterase-5 inhibitor, circumcision, and selective dorsal neurotomy (SDN). The previous study found that SDN is effective for PE. Methods and analysis: The electronic databases of MEDLINE, PubMed, Web of Science, EMBASE, Cochrane Library, Clinicaltrials. org, China National Knowledge Infrastructure Database (CNKI), Wan fang Database, China Biology Medicine Database (CBM), VIP Science Technology Periodical Database, Chinese Clinical Trial Registry will be retrieved. All the randomized controlled trials of selective dorsal penile neurotomy for patients with PE will be included. The outcome includes intravaginal ejaculation latency time and Chinese Index of Sexual Function for Premature Ejaculation-5. We will conduct this study strictly according to the Cochrane Handbook for Systematic Reviews of Interventions. Results: The present study is a protocol for systematic review and meta-analysis without results, and data analysis will be carried out after the protocol. We will share our findings on June 30th of 2021. Conclusion: SDN can effectively prolong IELT, but its efficacy has not been assessed scientifically and systematically. To address this limitation, this study will inspect the efficacy and safety of the SDN treatment in patients with PE. Ethics and dissemination: Formal ethical approval is not required in this protocol. We will collect and analyze data based on published studies, and since there are no patients involved in this study, individual privacy will not be under concerns. The results of this review will be disseminated to peer-reviewed journals or submit to related conferences. Protocol registration number: INPLASY202070084

Background and objectiveTo evaluate the relationship between erectile dysfunction (ED) and premature ejaculation (PE) among men aged 40–79 years and to compare age-related differences between men aged 40–59 years and 60–79 years.Materials and methodsFrom January 2014 to January 2019, records of 892 men aged 40–79 years were analyzed. We performed correlation analysis using the self-reported intravaginal ejaculation latency time (IELT), premature ejaculatory diagnostic tool (PEDT), Male Sexual Health Questionnaire-ejaculation (MSHQ-EjD), and International Index of Erectile Function5 (IIEF5) questionnaires.ResultsThe mean age of the 892 males was 52.8 ± 7.3 years (40–76). All subjects were divided into group 1 (40–59 years old) and group 2 (60–79 years old). The IIEF5 score of group 1 was significantly higher than that of group 2 (18.7 ± 5.5 vs. 17.7 ± 5.7, p = 0.049). Of the total subjects, 71 (8%) had IELT value of less than 1 min. A total of 51 (6.9%) and 20 (13.5%) were in groups 1 and 2, respectively (p = 0.02). The PEDT total score was higher and more subjects were identified as suffering from PE (PEDT ≥ 9) from amongst the ED subjects (IIEF-5 ≤ 21). In both groups 1 and 2, more PE subjects were identified in ED subjects (IIEF-5 ≤ 21) than normal subjects (IIEF-5 > 21) (all p < 0.01). In the total subjects, group 1 and 2, the IIEF-5 and PEDT score showed a weak negative correlation (r = −0.302, r = −0.361, r = −0.248, all p < 0.01). In group 2,the IELT and MSHQ-EjD score also showed a weak positive correlation between the IIEF-5 score (r = 0.166, p = 0.044 and r = 0.164, p = 0.047, respectively).ConclusionMore subjects defined PE value as less than 1 min on the self-reported IELT in the elderly group ≥60 years than those among the 40–59 years age group; moreover, the lower the IIEF5 total score among subjects ≥ 60 years, the higher the PEDT score and the lower the IELT and MSHQ-EjD scores.

Recently, the ICD-11 for Mortality and Morbidity Statistics (ICD-11-MMS, 2018 Version) has been published with a new definition of premature ejaculation (PE), including a third PE subtype. This definition differs from Diagnostic and Statistical Manual of Mental Disorders (DSM-5) definition of PE. We hereby address the similarities and differences between ICD-11-MMS and DSM-5 definition of PE and call attention to the illogical policy of some European (EU) National Regulatory Agencies to remain with a 1-min cut-off point of ejaculation time for Lifelong, Acquired and Subjective PE. The advantage of ICD-11-MMS is the inclusion of a third PE subtype, which is congruent with Subjective PE. A serious disadvantage of DSM-5 is that a 1-min criterion is used for both Lifelong and Acquired PE, and that a third PE subtype is not mentioned. Despite the incomplete DSM-5 definition of PE, some EU regulatory agencies adhere to a definition of PE which relies only on the 1-min ejaculation time cut-off point of DSM-5, and do not recognize the more recent PE definitions of ICD-11-MMS and International Society for Sexual Medicine. There is no scientific evidence for this illogical position. The continued use of a 1-min cut-off point for all subgroups of PE ignores the existence of Acquired PE (Intravaginal Ejaculation Latency Time (IELT)

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.

Purpose: To determine the role of metabolic syndrome (MetS) as a risk factor for acquired premature ejaculation (PE) after considering the various risk factors, such as lower urinary tract symptoms, erectile dysfunction, hypogonadism, and prostatitis. Materials and Methods: From January 2012 to January 2017, records of 1,029 men were analyzed. We performed multivari-ate analysis to identify risk factors for PE, including the covariate of age, marital status, International Prostate Symptom Score, International Index of Erectile Function (IIEF) score, National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) score, serum testosterone levels, and all components of MetS. Acquired PE was defined as self-reported intravaginal ejacula-tion latency time ≤3 minutes, and MetS was diagnosed using the modified National Cholesterol Education Program Adult Treatment Panel III criteria. Results: Of 1,029 men, 74 subjects (7.2%) had acquired PE and 111 (10.8%) had MetS. Multivariate analysis showed that the IIEF overall satisfaction score (odds ratio [OR]=0.67, p

The purpose of the study was to conduct a systematic evaluation of the different general prescribed drugs for premature ejaculation (PE). A systematic literature search of MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science for Systematic Reviews was performed on 1 March 2018. Intravaginal ejaculation latency time (IELT) was the main outcome. Analysis was performed under multivariate random-effects network model and efficacies of drugs were ranked with surface under the cumulative ranking (SUCRA) probabilities. A total of 48 studies were reviewed and 40 of them were further enrolled into network meta-analysis. The majority of RCTs were of unclear methodological quality. Pooled evidence suggested that topical anaesthetic creams (TAs), tramadol, selective serotonin reuptake inhibitors (SSRIs), and phosphodiesterase type 5 inhibitors (PDE5is) are more effective at prolonging IELT comparing with placebo. TAs (90%) on demand (OD) and PDE5is plus SSRI (89.8%) had the highest SUCRA, which meant the most probable to be the most effective intervention. We recommend the initial use of dapoxetine 30 mg OD for PE because it has been tested in largest and better designed clinical trials rather than it is more effective than the other drugs studied. TAs and tramadol 50 mg OD can be used as a viable alternative to oral treatment with SSRIs. PDE5is combined with SSRIs are more effective than SSRIs monotherapy but are also associated with more side effects. PDE5is OD can be recommended to PE patients with ED.

INTRODUCTION:This study explores the relationship between erectile function and ejaculatory function, to inform the clinical psychosexological and sexual medicine practice treatment protocols. MATERIALS AND METHODS:A total of 1,004 Czech males aged between 15 and 84 years (m = 42.8 yrs; sd = 17.6 years) completed a sexual behavior questionnaire. A cross-sectional design was adopted. Erectile function was measured with the International Index of Erectile Function (IIEF-5) and ejaculatory function measured using self-report intravaginal ejaculation latency time and the Index of Premature Ejaculation (IPE). Linear regression analyses were used to explore the relationships between premature ejaculation and erectile dysfunction. RESULTS:The sample mean self-reported intravaginal ejaculatory latency time was 9.34 minutes. The overall mean on the IPE was 19.44 (sd = 2.368). The Control domain mean was 81.13 (sd = 17.22); Sexual Satisfaction domain mean 78.60 (sd = 20.59); and the Distress domain mean was 86.86 (sd = 18.32). The mean score on the IIEF-5 was 19.28 (sd = 2.53). The results indicate a relationship between premature ejaculation and erectile dysfunction. With age significantly associated with all measures. CONCLUSIONS:Higher levels of erectile function are associated with a better control and sexual satisfaction, and less distress about ejaculation. This association supports the consideration of this relationship in the development of new clinical practice guidelines for erectile dysfunction and premature ejaculation.

Objectives: We recommend a new kind of spray made from eight kinds of traditional Chinese medicine, we aimed to investigate the safety and clinical efficacy of combined traditional Chinese medicine spray (TCMS) with premature ejaculation desensitization therapy (PEDT) for the treatment of primary premature ejaculation (PPE). Methods: A total of 90 patients with PPE were randomly assigned to receive TCMS, PEDT monotherapy or TCMS plus PEDT combination therapy for 6 weeks. Intravaginal ejaculation latency time (IELT) and Chinese index of sexual function for premature ejaculation (CIPE-5) were measured to evaluate the effect of each treatment. Results: Eighty six (86) participants completed the study voluntarily. Both IELT and CIPE-5 in these three groups increased after treatment when compared with baseline levels (p< 0.01). IELT and CIPE-5 after treatment in TCMS plus PEDT group were significantly higher than those in the other two groups (both p

To assess the correlation between penile hypersensitivity and premature ejaculation (PE), a total of 420 consecutive subjects attending our andrologic clinic for suspected PE were enrolled. The entire cohort was asked to complete the self-report intravaginal ejaculation latency time (IELT) by stopwatch. According to the IELT, the subjects were classified into 3 groups. Vibratory thresholds were recorded at the glans penis and penile shaft using a biothesiometer. We found that vibratory thresholds in the glans penis and penile shaft were significantly lower in both mild and severe PE group than in the control group (3.81 ± 0.57 and 3.54 ± 0.43 vs 4.73 ± 0.77 for glans penis p = 0.000; 3.64 ± 0.52 and 3.37 ± 0.50 vs 4.62 ± 0.69 for penile shaft p = 0.002). The vibratory threshold decreased as the disease aggravated. In the mild and severe PE groups, a significant positive correlation was detected between the mean values of IELT and the vibratory thresholds. Furthermore, in the receiver operating characteristics curve analysis, the area under the curve of the glans penis and penile shaft vibratory thresholds predicting severe PE were 0.852 and 0.893 respectively. Our study established a dose-dependent association between penile vibratory threshold and PE. Therefore, the vibratory threshold can serve as a potential marker for predicting the severity of PE.

Premature Ejaculation (PE) is a common male sex problem and incidence wise it is much commoner than erectile dysfunction with incidence in some studies being greater than 30% [1, 2]. In spite of this it does not attain enough attention of research workers. Ejaculation time (ET) may vary, but patient usually seeks medical help when it consistently becomes short at every coitus and causes distress to the couple. American Urological Association (AUA) defines PE when it “occurs sooner than desire” and causes “distress to one or both partners” [3]. For clinical assessment quantification is essential and in this case is possible by measuring Intravaginal Ejaculation Latency Time (IELT).this calculated by time period between vaginal penetration of phallus and intravaginal ejaculation. A more categorical and working definition comes from the International Society for Sexual Medicine (ISSM) which states that PE is “ejaculation that occurs prior to or within 1 minute of vaginal penetration” [4]. In our study we have taken IELT of less than 1 minute as PE. Serotonin has been found to have an inhibitory action on seminal emission/ejaculation via action on brain, brainstem, raphe nuclei and reticular formation. These observation leads to several studies which show that selective serotonin reuptake inhibitor (SSRI) achieve significant increase in IELT [5].

We investigated the prevalence of 5HT2C receptor gene polymorphisms in Egyptian patients with lifelong premature ejaculation. A total of 350 participants were enrolled in a prospective study. Two hundred and forty-five cases with lifelong premature ejaculation joined this study, in addition to 105 controls. We instructed the partners of the cases to measure the IELT of the first intercourse only using a stopwatch for 1 month. Genotyping was carried out at the end of the study. The results showed that the majority of the patients and controls were Cys/Cys. A highly significant statistical association was found between the studied gene polymorphisms and IELT among cases (p-values = .009). The study emphasised the potential role of 5HT2C receptor gene polymorphisms in patients with lifelong premature ejaculation.

Objectives: Premature ejaculation (PE) is a sexual disorder characterised by excessive rapidity of orgasm. It is defined as either primary (60%), present since the onset of sexual activity, or secondary (40%), manifesting later in life. To date, dapoxetine is the only preparation approved for the on-demand treatment of PE. However, side effects, costs associated with the treatment of chronic PE, drug dependence and its variable effectiveness leads to a not insignificant drop-out rate. Dynamic rehabilitative/behavioural therapy may be a viable therapeutic option, working alongside pharmacological treatment, as long as the participation and involvement of both the individual and the couple is optimal. Materials and methods: 18 patients were enrolled, aged between 25 and 55 (mean: 40), all with primary PE, free of comorbidities and with their partners involved. Six patients were prescribed 30 mg dapoxetine two hours before sexual relations for 3 months (group A); 6 patients began the dynamic rehabilitative treatment (group B); 6 other couples were assigned to pharmacological treatment in association with dynamic rehabilitative behavioural treatment for 3 months (group C). Division of subjects was carried out by simple randomisation, excluding patients with a short frenulum, phimosis, ED, chronic prostatitis or experiencing results from previous treatment. Results: Outcomes of treatment were evaluated at the end of the 3 months of treatment and 3 months after discontinuing treatment. In Group A 75% of patients were cured at 3 months and 25% at 6 months. In Group B 25% patients were cured at 3 months and 25% at 6 months. In Group C 75% of patients were cured 3 months and 50% at 6 months. "Cured" means a Premature Ejaculation Diagnostic Tool (PEDT) score reduced from an average of 12 to an average of 6 and Intravaginal Ejaculation Latency Time (IELT) values from < 1 to > 6 minutes. Conclusions: the integration of pharmacological treatment with dynamic behavioural rehabilitation has the specific aim of optimising and stabilising the results, supporting a more efficient recovery of ejaculatory control. The close involvement of the partner is extremely useful for all results.

Oral drug treatment for PE has been available since 1932 when Bernard Schapiro developed Prajaculin for the treatment of lifelong PE, which was even more than a decade before the first review article on PE was published by Schapiro in 1943 and long before behavioral treatments were advocated as the first choice of treatment. However, it was only after the introduction of the selective serotonin reuptake inhibitors (SSRIs) in the early 1990s that drug treatment of PE became revolutionized. Lack of an operationalized definition of PE and the absence of an objective measure of the ejaculation time hampered a truly scientific approach to investigate the efficacy of drugs in delaying ejaculation. Waldinger et al. introduced in 1994 the intravaginal ejaculation latency time (IELT) as a standardized measure of the ejaculation time. Various drugs are currently available for the treatment of PE, but all of them, except dapoxetine, are off-label. This chapter will discuss current treatments of PE with their advantages and disadvantages including daily treatment with SSRIs, on-demand treatment with oral drugs and topical anesthetics, and psychosocial treatments.

Objective To determine the relationship between postcircumcisional mucosal cuff length due to performance of circumcision and premature ejaculation (PE). Materials and methods 180 circumcised men were enrolled in the study, including 60 men with PE circumcision performed by doctors (Group 1), 60 men with PE circumcision performed by non-medical personnel (Group 2) and 60 men without PE. Data considered for analysis consisted of age, circumcision age, education, smoking, penile length, mucosal cuff, penile skin lengths and Intravaginal Ejaculation Latency Time (IELT). Results The mean age of study group was 32.7 ± 10.4 (range 24–56). The mean of IELT was 0.6 ± 0.1 min (min) in group 1, 0.5 ± 0.1 min in Group 2 and 4.3 ± 0.3 min in healthy group. The mean of penis length was 123.2 ± 12.8 mm in group 1, 124.6 ± 11.7 mm in group 2 and 124.8 ± 13.4 mm in healthy group. The mean of penile mucosa was 11.7 ± 1.7 mm in group 1, 14.8 ± 3.1 mm in group 2 and 12.8 ± 3.1 mm in healthy group. There was no difference between the three groups regarding the length of the penile mucosal cuff (p = 0.89). Patients circumcised by doctors in group 1 had significantly shorter postcircumcisional mucosal cuff length than group 2 patients circumcised by personnel except doctors (p = 0.42); but there was no statistical difference in IELT between group 1 and group 2. Conclusions The result of this study is that circumcisions performed by doctors have shorter mucosal cuff but the length of mucosa is not a risk factor in premature ejaculation.