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Concept: Premature ejaculation

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OBJECTIVE: To investigate the efficacy of DA-8031, a novel compound for the treatment of premature ejaculation (PE), we performed in vivo pharmacological studies using 2 preclinical animal models, electrical stimulation of sensory branch of pudendal nerve (SBPdn) and para-chloroamphetamine (PCA)-induced ejaculation model. METHODS: First of all, in electrical stimulation of an SBPdn model, an SBPdn in the pelvic canal of the spinal cord transected from rats was identified. Then an electromyogram (EMG) of the bulbospongiosus (BS) muscle was recorded during electrical stimulation of SBPdn after single intravenous (IV) dosing of DA-8031 and its reference drug, dapoxetine. In the second model, both seminal vesicle pressure (SVP) and the EMG profile of the BS muscle were recorded in PCA-induced ejaculation animals after treated with the same dosing regimen. RESULTS: Area under the curve (AUC) of the BS muscle by EMG wave exhibited a significant reduction in the DA-8031 and dapoxetine 3 mg/kg treated groups, and maximum amplitudes were also significantly decreased in DA-8031 1, 3 mg/kg and dapoxetine 3 mg/kg dose level in the SBPdN stimulation model. Consistent with these findings, in a PCA-induced ejaculation model, SVP increase was significantly inhibited from DA-8031 0.3 mg/kg dose level, and AUC of BS muscle EMG significantly decreased in the DA-8031 1, 3 mg/kg groups. CONCLUSION: The present study implied that DA-8031 contributed to an effective co-coordinated inhibition of the expulsion phase of ejaculation by modulating BS muscle activity and the emission phase through blocking SVP rise. From these findings, DA-8031 is further expected to have clinical efficacy in human studies.

Concepts: Semen, Electromyography, Orgasm, Ejaculation, Penis, Premature ejaculation, Pudendal nerve, Bulbospongiosus muscle

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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.

Concepts: Andrology, Receiver operating characteristic, Orgasm, Ejaculation, Penis, Premature ejaculation, Glans penis, Intravaginal ejaculation latency time

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Traditional factors that once explained men’s sexual difficulties appear insufficient to account for the sharp rise in erectile dysfunction, delayed ejaculation, decreased sexual satisfaction, and diminished libido during partnered sex in men under 40. This review (1) considers data from multiple domains, e.g., clinical, biological (addiction/urology), psychological (sexual conditioning), sociological; and (2) presents a series of clinical reports, all with the aim of proposing a possible direction for future research of this phenomenon. Alterations to the brain’s motivational system are explored as a possible etiology underlying pornography-related sexual dysfunctions. This review also considers evidence that Internet pornography’s unique properties (limitless novelty, potential for easy escalation to more extreme material, video format, etc.) may be potent enough to condition sexual arousal to aspects of Internet pornography use that do not readily transition to real-life partners, such that sex with desired partners may not register as meeting expectations and arousal declines. Clinical reports suggest that terminating Internet pornography use is sometimes sufficient to reverse negative effects, underscoring the need for extensive investigation using methodologies that have subjects remove the variable of Internet pornography use. In the interim, a simple diagnostic protocol for assessing patients with porn-induced sexual dysfunction is put forth.

Concepts: Sexual intercourse, Erectile dysfunction, Orgasm, Penis, Premature ejaculation, Erection, Sexual arousal, Sexual dysfunction

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INTRODUCTION: Erectile dysfunction (ED) is a common complaint in men over 40 years of age, and prevalence rates increase throughout the aging period. Prevalence and risk factors of ED among young men have been scantly analyzed. AIM: Assessing sociodemographic and clinical characteristics of young men (defined as ≤40 years) seeking first medical help for new onset ED as their primary sexual disorder. METHODS: Complete sociodemographic and clinical data from 439 consecutive patients were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients completed the International Index of Erectile Function (IIEF). MAIN OUTCOME MEASURE: Descriptive statistics tested sociodemographic and clinical differences between ED patients ≤40 years and >40 years. RESULTS: New onset ED as the primary disorder was found in 114 (26%) men ≤40 years (mean [standard deviation [SD]] age: 32.4 [6.0]; range: 17-40 years). Patients ≤40 years had a lower rate of comorbid conditions (CCI = 0 in 90.4% vs. 58.3%; χ(2) , 39.12; P < 0.001), a lower mean body mass index value (P = 0.005), and a higher mean circulating total testosterone level (P = 0.005) as compared with those >40 years. Younger ED patients more frequently showed habit of cigarette smoking and use of illicit drug, as compared with older men (all P ≤ 0.02). Premature ejaculation was more comorbid in younger men, whereas Peyronie’s disease was prevalent in the older group (all P = 0.03). At IIEF, severe ED rates were found in 48.8% younger men and 40% older men, respectively (P > 0.05). Similarly, rates of mild, mild-to-moderate, and moderate ED were not significantly different between the two groups. CONCLUSIONS: This exploratory analysis showed that one in four patients seeking first medical help for new onset ED was younger than 40 years. Almost half of the young men suffered from severe ED, with comparable rates in older patients. Overall, younger men differed from older individuals in terms of both clinical and sociodemographic parameters. Capogrosso P, Colicchia M, Ventimiglia E, Castagna G, Clementi MC, Suardi N, Castiglione F, Briganti A, Cantiello F, Damiano R, Montorsi F, and Salonia A. One patient out of four with newly diagnosed erectile dysfunction is a young man-worrisome picture from the everyday clinical practice. J Sex Med **;**:**-**.

Concepts: Testosterone, Mental disorder, Prevalence, Erectile dysfunction, Comorbidity, Penis, Premature ejaculation, Sexual dysfunction

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Premature ejaculation (PE) is the most common sexual disorder. It affects 20%-30% of adult men; the aetiology of this condition has not yet been elucidated. The aim of this study is to evaluate the efficacy, safety, tolerability, undesirable effects and improved satisfaction with sexual intercourse with tramadol hydrochloride at different dosages for the treatment of PE. A total of 300 patients who presented with lifelong (primary) PE were included in this study. The study was performed for 28 weeks, in which placebo (starch tablet) was given for 4 weeks, and active ingredient (tramadol hydrochloride) was administered at different therapeutic dosages for 24 weeks. Patients were divided into three equal groups, each consisting of 100 patients. The first group (A) was given tramadol hydrochloride capsule 25 mg. The second group (B) was given tramadol hydrochloride capsule 50 mg. The third group © was given tramadol hydrochloride capsule 100 mg. All of the 300 participants included completed the study voluntarily. The age of the patients varied from 25 to 50 years. After the treatment period, the recorded data were collected for each group and analysed. The results showed a highly significant increase in the mean intravaginal ejaculatory latency time (IELT) in all groups compared to baseline data (P<0.0001). We concluded that using tramadol hydrochloride at different doses on demand for the treatment of PE is effective, safe and tolerable, with minimal undesirable effects, and approval for this indication should be sought.

Concepts: Effectiveness, Selective serotonin reuptake inhibitor, Orgasm, Ejaculation, Penis, Premature ejaculation, Sexual dysfunction, Intravaginal ejaculation latency time

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PURPOSE: In our previous study, we showed that there was a significant increase in the prevalence of monosymptomatic enuresis (ME) among lifelong premature ejaculators. In this study, we aimed to compare the intravaginal ejaculatory latency time (IELT) of men with and without history of ME and to determine the association between the severity and duration of ME and IELT in healthy men. MATERIALS AND METHODS: Between March and September 2012, we designed a prospective study in 49 healthy men who had history of ME and in age-matched 49 control cases without a history of ME. All subjects were asked about their history of ME. Each were then evaluated using the Premature Ejaculation Diagnostic Tool (PEDT) and asked to measure their IELTs, by their female sexual partner using a calibrated stopwatch. RESULTS: Men with history of ME and control cases had a mean (SD, range) age of 33.6 (4.7, 25-43) and 33.8 (5.4, 25-48) years respectively (P=0.97). The mean/median IELT of men with and without history of ME were 196.9/126.2 and 426.6/343.2 seconds respectively (P<0.001). The mean/median PEDT score of men with and without history of ME were 7.1/6 and 2.3/2 respectively (P<0.001). In correlation matrix analysis, IELTs and PEDT scores were correlated significantly with having history, duration and severity of ME (P<0.001). CONCLUSIONS: We have found that IELT in men with history of ME is significantly shorter than the IELT of control cases. We have also shown that there is a strong negative correlation between having ME history and IELT.

Concepts: Epidemiology, Urology, Correlation and dependence, Orgasm, Ejaculation, Penis, Premature ejaculation, Intravaginal ejaculation latency time

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Abstract Objective. The etiology of premature ejaculation (PE) is unknown. Over the past two decades several studies have suggested that lifelong and acquired PE may be caused by somatic disorders and/or neurobiological disturbances. One controversial factor is the effect of circumcision on ejaculation. This prospective study investigated the relationship between postcircumcision penile mucosal cuff length, circumcision scar thickness and the PE syndromes. Features of PE patients were compared with those of a normal healthy control (NHC) group. Material and methods. In total, 160 circumcised men were studied: 80 men with PE and 80 men in the NHC group. The following data and measurements were evaluated: age, type of PE syndrome, intravaginal ejaculation latency time (IELT), circumcision scar thickness and postcircumcision mucosal cuff length. Results. In terms of the mean IELT, a statistically significant difference was detected between the PE syndromes (p < 0.05), and between the PE patients and the control group (p < 0.05). Among the four PE syndromes, there was no significant difference related to the mean mucosal cuff length and mean circumcision scar thickness (p > 0.05). No significant difference was observed between the two groups for mean mucosal cuff length (p > 0.05) or mean circumcision scar thickness (p > 0.05). Conclusion. In this study, no relationship was observed between PE and postcircumcision penile mucosal cuff length and circumcision scar thickness. Further studies are required to evaluate the positive and negative effects of circumcision on PE syndromes.

Concepts: Statistical significance, Foreskin, Ejaculation, Penis, Premature ejaculation, Circumcision, Glans penis, Intravaginal ejaculation latency time

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PURPOSE: To evaluate expansion of image-guided interventional cryoablation techniques usually employed for pain management to address the feasibility, safety, and efficacy of treatment for a urologic condition with otherwise limited treatment options, premature ejaculation (PE). MATERIALS AND METHODS: Prospective institutional review board approval was obtained, and 24 subjects with PE were enrolled. All patients underwent unilateral percutaneous computed tomography-guided cryoablation of the dorsal penile nerve (DPN). Postprocedural intravaginal ejaculatory latency times (IELTs) and PE Profile (PEP) results served as outcome variables. In addition, subjects were asked whether they would have the procedure done again based on their experience at the 180- and 360-day marks. RESULTS: The technical success rate was 100%. Baseline average IELT was 54.7 seconds±7.8 (n = 24), which increased to a maximum of 256 seconds±104 (n = 11; P = .241) by day 7 and decreased to 182.5 seconds±87.8 (n = 6; P = .0342) by day 90. The mean IELT remained at 182.5 seconds±27.6 at day 180 (n = 23; P<.0001) and decreased to 140.9 seconds±83.6 by 1 year (n = 22; P<.001). PEP scores improved overall, IELTs significantly improved at 180 and 360 days, and 83% of subjects reported that they would undergo the procedure again if given the same opportunity. There were no procedure-related complications. CONCLUSIONS: CT-guided percutaneous unilateral cryoablation of the DPN is a feasible, safe, single-day outpatient procedure for the treatment of symptomatic PE.

Concepts: Urology, Andrology, Arithmetic mean, Orgasm, Ejaculation, Penis, Premature ejaculation, Intravaginal ejaculation latency time

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The aim of the study is to investigate whether there is an effect of adult circumcision on ejaculation parameters and to research the relationship between intravaginal ejaculation latency time (IELT) and premature ejaculation diagnostic tool (PEDT). Adults who underwent voluntary circumcision between September 2010 and November 2011 were enrolled in this prospective study. The IELT before and 3 months following circumcision was recorded. Also, PEDT was filled out before and 3 months after circumcision. During statistical evaluation, the comparison of situations before and after circumcision was made using IELT averages and PEDT total scores. Furthermore, the correlation between changes in IELT and PEDT has also been evaluated. A total of 30 volunteers (mean age 21.25±0.44) were enrolled in the study. The volunteers' mean and median IELT before were 104.36±66.21 and 88 (26-307) seconds, whereas mean and median IELT after circumcision were 123.56±54.44 and 107.5 (67-300) seconds, respectively. The increase after circumcision was statistically significant (P=0.001). The mean and median PEDT score were 4.26±2.91 and 3 (1-12) before, and 2.63±1.82 and 2 (0-7) after circumcision. Improvement was statistically significant (P<0.0001). No correlation could be found between ejaculation time and PEDT scores. Circumcision during adulthood does not adversely affect ejaculatory function; it may slightly improve. However, it could not be interpreted as a justification for circumcision in men with premature ejaculation (PE).International Journal of Impotence Research advance online publication, 2 January 2014; doi:10.1038/ijir.2013.47.

Concepts: Statistics, Arithmetic mean, Mean, Ejaculation, Penis, Premature ejaculation, Sexual dysfunction, Intravaginal ejaculation latency time

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Objective: This systematic review was performed to evaluate the efficacy and safety of tramadol in patients with premature ejaculation (PE). Methods: A systematic search of PubMed®, Embase® and the Cochrane Library was performed to identify all randomized controlled trials (RCTs) that compared the effects of tramadol with placebo or no drug for patients with PE. The outcomes included post-therapeutic intravaginal ejaculation latency time (IELT), increases in IELT, satisfaction with sexual intercourse, control over ejaculation and side effects (SEs). The Cochrane Collaboration Review Manager software (RevMan 5.1.4) was used for statistical analysis. Results: A total of 5 trials, involving 715 patients, met the inclusion criteria. The synthesized data from these RCTs indicated that compared with the control, tramadol significantly increased IELT values post-therapeutically (SMD 3.51, 95% CI 2.14-4.88, p < 0.00001) and changes in IELT values were more pronounced in the tramadol group (SMD 2.87, 95% CI 2.63-3.10, p < 0.00001). Satisfaction with sexual intercourse and the ability to control ejaculation were both improved in patients in the tramadol group (p < 0.05). The incidence of SEs in the tramadol group were significantly higher than in the control group (RR 3.55, 95% CI 1.34-9.40, p = 0.01), however most SEs were mild or moderate and transient. Conclusions: Tramadol may be effective in PE treatment, especially when patients have failed therapies, like selective serotonin reuptake inhibitors. However, the possibility of drug addiction and SEs should still be considered before initial use or after chronic use of this agent. More high-quality (clear randomization sequences, allocation concealment and blinding introduction), long-term, RCTs with a large number of PE patients are expected.

Concepts: Evidence-based medicine, Cochrane Collaboration, Systematic review, Cochrane Library, Randomized controlled trial, Selective serotonin reuptake inhibitor, Premature ejaculation, Intravaginal ejaculation latency time