Treatment benefit of dapoxetine for premature ejaculation: results from a placebo‐controlled phase III trial

OBJECTIVE

To evaluate the overall treatment benefit of dapoxetine for premature ejaculation (PE), with specific emphasis on improvements in personal distress and interpersonal difficulty related to ejaculation. Although these factors are key elements of numerous sets of diagnostic criteria for PE, they have rarely been evaluated as outcome measures in clinical trials.

PATIENTS AND METHODS

In this randomized, double‐blind, placebo‐controlled, phase III trial we enrolled men aged ≥18 years, from the USA and Canada, who had a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, diagnosis of PE (1238 men). Men were randomized to receive placebo or dapoxetine 60 mg as needed or once daily for 9 weeks. The once‐daily treatment arm was included for analysis of withdrawal symptoms (primary endpoint; presented elsewhere). Patients completed the Premature Ejaculation Profile (PEP) on day 1 (before dosing), and on days 28 and 63 (or study endpoint), which comprised the outcome measures for perceived control over ejaculation, satisfaction with sexual intercourse, and personal distress and interpersonal difficulty related to ejaculation. The patient‐reported global impression of change in PE was reported on day 63 (or study endpoint). Treatment benefit measures included the composite criteria of at least a two‐category increase in perceived control over ejaculation and at least a one‐category decrease in personal distress related to ejaculation from baseline at study endpoint.

RESULTS

At baseline, ≈5% of patients in any treatment group reported ‘not at all’ or ‘a little bit’ of personal distress related to ejaculation, which increased to 54.3% of those receiving dapoxetine (vs 35.3% with placebo; P < 0.001). Similarly, 43.0% and 40.9% of men in the placebo and dapoxetine groups, respectively, reported ‘not at all’ or ‘a little bit’ of interpersonal difficulty related to ejaculation at baseline, which increased to 76.8% and 64.2% of those with dapoxetine and placebo, respectively (P < 0.001). The percentage of men who achieved the composite criteria with dapoxetine ‘as needed’ was 47.6%, vs 21.7% with placebo (difference from placebo, 25.9%; P < 0.001). The distribution of responses for the PEP among men who achieved the composite criteria was similar to that reported for men without PE in a previous observational study in the USA. The most common adverse events were nausea, dizziness, headache, diarrhoea and insomnia, which were more common with dapoxetine than with placebo.

CONCLUSION

Dapoxetine reduced the personal distress and interpersonal difficulty associated with PE, and was associated with patient‐reported improvements in their condition. The percentage of patients who achieved a composite of a two‐category or greater increase in perceived control over ejaculation and a one‐category or greater decrease in personal distress related to ejaculation was substantially greater than with placebo, as were all outcome measures.     

Evolving therapeutic strategies for premature ejaculation: The search for on-demand treatment �C topical versus systemic

Premature ejaculation (PE) is a common sexual dysfunction affecting 20% to 30% of men worldwide. Definitions of PE vary, but it is typically characterized by short intravaginal ejaculatory latency time (IELT) with concomitant sexual dissatisfaction and distress. PE may be lifelong or acquired, but its etiology remains unclear. Treatment of PE typically involves pharmacotherapy, particularly when lifelong. Although there are numerous reports on the off-label use of selective serotonin reuptake inhibitors (SSRIs) and other compounds, only 2 treatments have been evaluated in randomized controlled phase 3 clinical trials: PSD502 and dapoxetine (SSRI). Both significantly improved IELT and patient-reported outcome domains of ejaculatory control, sexual satisfaction, and distress as measured by the index of premature ejaculation (IPE), compared with placebo. They constitute the focus of this review. Evidence demonstrated that PSD502, dapoxetine and other SSRIs all significantly improve the symptoms of PE. Systemic use of SSRIs presents risks associated with the known pharmacology of this class. PSD502 allows for topical on-demand treatment applied applied immediately before intercourse, and is not associated with systemic adverse events.     

Treatment of premature ejaculation: new drugs and treatment strategies

This review discusses treatment options for men with premature ejaculation (PE), a common sexual dysfunction characterized by short ejaculatory latency, decreased sexual satisfaction, and distress. For a number of reasons, including embarrassment and the belief that PE is a normal part of aging, has no effective treatment, or will resolve itself, few men with PE seek treatment. Although several treatment options exist (eg, behavioral, cognitive, and sex therapy methods; desensitizing drugs; off-label use of antidepressants and/or phosphodiesterase type 5 inhibitors or α-blockers), the majority of men with PE generally are not satisfied with their results. New pharmacologic drugs, specifically for the treatment of PE, are undergoing evaluation in clinical trials. As an example, recent clinical research studies have revealed on-demand administration of one such drug, dapoxetine, which achieved significant improvements in ejaculatory latency, control over ejaculation, and satisfaction with sexual intercourse. In addition, partners of men who received dapoxetine likewise reported improved satisfaction with sexual intercourse. Future studies may reveal that integration of pharmacologic drugs with psychologic and/or behavioral therapy techniques may be the optimal approach to the management of PE. PE is a treatable condition, and new drugs in development may provide benefits over those available.     

Correlates to the clinical diagnosis of premature ejaculation: results from a large observational study of men and their partners

PURPOSE: A recent observational study characterized intravaginal ejaculatory latency time and single item patient reported outcome measures in a large population of males with and without premature ejaculation, as well as their female partners. In the current analysis we assessed the relative influence of those measures in identifying premature ejaculation as diagnosed by the clinician. MATERIALS AND METHODS: Data were from a 4-week, multicenter, observational study of men with (207) and without (1,380) premature ejaculation (diagnosed using The Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision criteria), as well as their female partners. Estimated and measured intravaginal ejaculatory latency time, age, and responses to single item (control over ejaculation, personal distress, satisfaction with sexual intercourse and interpersonal difficulty) and multiple item (male and female Golombok-Rust Inventory of Sexual Satisfaction, male Self-Esteem and Relationship questionnaire, and Short Form 36) measures were evaluated with stepwise logistic regression analysis. RESULTS: Self-estimated and stopwatch measured intravaginal ejaculatory latency time were interchangeable, correctly assigning premature ejaculation status with 80% sensitivity and 80% specificity, increasing to 80% sensitivity and 96% specificity when combined with single item patient reported outcomes. Subject reported control over ejaculation and personal distress most strongly indicated premature ejaculation status. Partner personal distress was more influential in determining premature ejaculation status than estimated or measured intravaginal ejaculatory latency time, and single item measures were more influential than multiple item measures. Age was not influential in assigning premature ejaculation status. CONCLUSIONS: Neither self-estimated nor stopwatch measured intravaginal ejaculatory latency time alone was optimal for assigning premature ejaculation status. Subject and partner responses to single item measures, particularly control over ejaculation and personal distress, were important. Results suggest that a combination of estimated intravaginal ejaculatory latency time and the 4 single item patient reported outcome measures can adequately identify premature ejaculation status.     

The Impact of Premature Ejaculation on Partners and Relationships

ObjectivesPremature ejaculation (PE) is a common condition in adult males that remains underdiagnosed and undertreated, partially because the sensitive nature of the topic discourages open discussions between affected males, their partners, and physicians. In addition to reduced sexual satisfaction, PE can have emotional consequences such as distress and dissatisfaction with the overall relationship, not only for the males but also their partners, the perspectives of whom have not been widely studied.MethodsAn online survey of female partners of men with PE was conducted to determine how the condition affects women and their relationships.ResultsThe results revealed that the relatively short intravaginal ejaculatory latency time (IELT) associated with PE causes emotional distress for the female partners (N = 115). The majority of female partners wanted to experience a prolonged IELT and considered that this would enhance both their sexual and overall relationship with their partner.ConclusionsIncreased awareness of the nature of the emotional and relationship ramifications of PE on men and their sexual partners should enhance the development of treatment options beyond pharmacotherapy alone.     

The Premature Ejaculation Profile: validation of self-reported outcome measures for research and practice

OBJECTIVE

To evaluate the reliability and validity of the Premature Ejaculation Profile (PEP), a self‐reported outcome instrument for evaluating domains of PE and its treatment, comprised of four single‐item measures, a profile, and an index score.

SUBJECTS AND METHODS

Data were from men participating in observational studies in the USA (PE, 207 men; non‐PE, 1380) and Europe (PE, 201; non‐PE, 914) and from men with PE (1238) participating in a phase III randomized, placebo‐controlled clinical trial of dapoxetine. The PEP contains four measures: perceived control over ejaculation, personal distress related to ejaculation, satisfaction with sexual intercourse, and interpersonal difficulty related to ejaculation, each assessed on five‐point response scales. Test‐retest reliability, known‐groups validity, and ability to detect a patient‐reported global impression of change (PGI) in condition were evaluated for the individual PEP measures and a PEP index score (the mean of all four measures). Profile analysis was conducted using multivariate analysis of variance.

RESULTS

All PEP measures showed acceptable reliability (intraclass correlation coefficients ranged from 0.66 to 0.83) and mean scores for all measures differed significantly between PE and non‐PE groups (P < 0.001). Men who reported a reduction in PE with treatment in the phase III trial had significantly greater scores on each of the four measures. The PEP profiles of men with and without PE differed significantly (P < 0.001) in both observational studies; higher levels of PGI were associated with higher PEP profiles (P < 0.001). The PEP index score also showed acceptable reliability and was significantly different between the PE and non‐PE groups (P < 0.001). Men who reported an improvement in PE with treatment in the phase III trial had significantly greater PEP index scores. In the phase III trial, nausea was the most common adverse event with dapoxetine.

CONCLUSION

The PEP provides a reliable, valid, and interpretable measure for use in monitoring outcomes of men with PE.     

PSD502 improves ejaculatory latency,control and sexual satisfaction when applied topically 5 min before intercourse in men with premature ejaculation: results of a phase III,multicentre, double‐blind,placebo‐controlled study

OBJECTIVES

To determine the effect of PSD502 applied topically 5 min before intercourse on the Index of Premature Ejaculation (IPE) and intravaginal ejaculatory latency time (IELT) of men with lifelong premature ejaculation (PE) defined according to the International Society of Sexual Medicine (ISSM) definition; secondary objectives were to evaluate the safety and tolerability of PSD502 in patients with PE, and their sexual partners.

PATIENTS AND METHODS

Men aged >18 years, in stable heterosexual, monogamous relationships, and with lifelong PE diagnosed according to both the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (text revision) criteria and the ISSM definition, consented (together with their partners) to enter the baseline period of the study. Patients who documented an IELT of ≤1 min with two or more of the first three sexual encounters during the 4‐week baseline period were randomized, in a 2:1 ratio, to receive double‐blind treatment with PSD502 (three actuations of spray each containing 7.5 mg lidocaine and 2.5 mg prilocaine applied 5 min before intercourse) or placebo for 3 months. Patients completed IPE and Premature Ejaculation Profile (PEP) questionnaires at entry and at monthly clinic visits, and recorded stopwatch‐timed IELT during each sexual encounter. Patients rated the quality of their orgasms on a 5‐point scale at baseline and at the end of the treatment period, and rated the study medication on a 4‐point scale. Safety was assessed by collecting adverse event data.

RESULTS

In all, 300 men with PE were randomized from 31 centres in Europe. The geometric mean (range) IELT over the 3‐month treatment period increased from a baseline of 0.6 min in both groups to 3.8 (0.3–57.8) and 1.1 (0–15.0) min in the PSD502 and placebo groups, respectively. Adjusting for treatment‐group imbalances, this represents a 6.3‐fold and 1.7‐fold increase in adjusted geometric means. There were significantly greater increases in the scores for the IPE domains of ejaculatory control and sexual satisfaction in the PSD502 group than in the placebo group, with a mean (sem ) 7.0 (0.59)‐point difference between treatments in change from baseline in the IPE domain for ejaculatory control and a 5.9 (0.57)‐ point difference in change from baseline in the IPE domain for sexual satisfaction (both P < 0.001). This was supported by improvements in all secondary endpoints. At the end of the treatment period 66% of patients rated PSD502 as ‘good’ or ‘excellent’. PSD502 was well tolerated and no systemic adverse events were reported. Localized treatment‐related adverse events were reported by 2.6% and 3.1% of patients and partners, respectively.

CONCLUSION

PSD502 applied topically 5 min before intercourse improved ejaculatory latency and significantly improved ejaculatory control and sexual satisfaction, factors relevant for acceptance of a PE treatment by both patient/physician and regulatory authorities. PSD502 was well tolerated by both patients and partners, with no systemic side‐effects and a low incidence of localized effects, and was rated favourably by most users. PSD502 therefore appears to offer significant advantages over other therapies in development for the treatment of PE.     

The psychological burden of premature ejaculation

PURPOSE: Premature ejaculation is characterized by short ejaculatory latency, inability to control ejaculation and resultant overall decreased sexual satisfaction for the man and his partner. Diagnostic criteria typically include aspects of psychological well-being. To motivate and justify treatment for premature ejaculation a more comprehensive understanding of its impact on men, their partners and their overall relationship is needed. MATERIALS AND METHODS: In a community based, observational study of 1,587 men and their female partners clinicians diagnosed premature ejaculation using Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision criteria. For purposes of this analysis this group was further restricted to subjects with a stopwatch measured intravaginal ejaculatory latency time of 2 minutes or less. Responses to the Premature Ejaculation Profile, Self-Esteem and Relationship questionnaire, Golombok-Rust Inventory of Sexual Satisfaction and Medical Outcomes Study SF-36 were compared between premature ejaculation and nonpremature ejaculation groups. Correlations between responses of men and partners were assessed for the Premature Ejaculation Profile and Golombok-Rust Inventory of Sexual Satisfaction. Correlations among patient reported measures enabled the assessment of independence of outcome variables. RESULTS AND CONCLUSIONS: Of 207 men who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision criteria 89 had an intravaginal ejaculatory latency time of 2 minutes or less. Lower levels of sexual functioning and satisfaction, and higher levels of personal distress and interpersonal difficulty were reported by men with premature ejaculation and their partners. In addition, men with premature ejaculation rated their overall quality of life lower than that of men without premature ejaculation. Consequently premature ejaculation has a significant psychological burden on men, their partners and the male/partner relationship.     

Perceived control over ejaculation is central to treatment benefit in men with premature ejaculation: results from phase III trials with dapoxetine

OBJECTIVES

To assess the utility of perceived control over ejaculation (‘control’) in the evaluation of treatment benefit in men with premature ejaculation (PE), and to compare effects associated with a two‐category or greater increase in this variable between men receiving dapoxetine and placebo.

PATIENTS AND METHODS

This subanalysis used combined data from all treatment groups in an integrated analysis of two identically designed, 12‐week, double‐blind, randomized, placebo‐controlled trials of dapoxetine. Men (2614) met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition, text revision) criteria for PE, had a stopwatch‐measured intravaginal ejaculatory latency time (IELT) of ≤2 min in ≥75% of events in a 2‐week baseline period, and self‐reported moderate or severe PE. Men received placebo or dapoxetine 30 or 60 mg, 1–3 h before intercourse. The stopwatch‐measured IELT was recorded for each episode; the patient‐reported global impression of change (PGI; 7‐point scale, ‘much worse’ to ‘much better’), control and satisfaction with sexual intercourse (5‐point scales, ‘very poor’ to ‘very good’) were assessed monthly. The utility of a two‐category or greater increase in control was evaluated by examining the relationship of this variable with IELT and satisfaction with sexual intercourse.

RESULTS

Of 2341 men with baseline and endpoint assessments, 96.8% reported ‘very poor’ or ‘poor’ control at baseline, and 748 (32%) reported a two‐category or greater increase in control after treatment. More than 95% of those men rated their PE as ‘slightly better’, ‘better’, or ‘much better’ on the PGI; 67.1% gave ratings of ‘better’ or ‘much better.’ They also had greater improvements in IELT than men with less than a two‐category increase in control, with a mean (sd ) change from baseline of 3.7 (4.3) vs 0.77 (1.8) min, respectively, and a greater percentage reported good or very good satisfaction with sexual intercourse than men with less than a two‐category increase in control (74% vs 19%, respectively). Nausea, headache and upper respiratory tract infection were the most common adverse events reported by men with a two‐category or greater increase in control (15.8%, 7.4% and 6.6%, respectively) and those without (8.5%, 5.5% and 6.5%, respectively). The proportions of men with a two‐category or greater increase in control with dapoxetine 30 and 60 mg were 36.3% and 44.5%, respectively (vs 15% with placebo).

CONCLUSIONS

A two‐category or greater increase in control (5‐point scale) is useful for assessing the treatment benefit in men with PE; it corresponds with improvements in the man’s perception of his condition, substantially greater prolongation of IELT, and higher levels of satisfaction with sexual intercourse.     

Der vorzeitige Samenerguss (Ejaculatio praecox)

With prevalence rates of 20%–25% premature ejaculation (PE) represents the most frequent sexual dysfunction in men. Whereas genetically determined changes in the serotonin receptor-/transporter mechanism seem to be responsible for lifelong PE, acquired PE is often associated with other conditioning diseases such as erectile dysfunction, prostatitis or thyroid dysfunctions. Typical features of PE are a short intravaginal ejaculatory latency time (IELT) <1–2 min, lack of control over ejaculation, personal distress and partner problems. Treatment of PE subdivides into sexual therapy as well as drug therapy. Among the medications considered for PE, oral therapy with selective serotonin re-uptake inhibitors (SSRI), Dapoxetine (the first officially approved medication for PE) and topical therapy with lidocaine/prilocaine-containing medications are given priority.     

Premature Ejaculation,True or False? Clinical evaluation of PE patients with multiple intercourse in one day

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.     

Premature ejaculation in couples using contraceptive withdrawal and associations with characteristics of its use: A cross-sectional study

This study aimed to investigate the Premature Ejaculation Profile (PEP) and its related factors in couples using contraceptive withdrawal (WD). The study sample was composed of 108 participants including 54 males and 54 females (their partners) who used WD. The data were collected via a questionnaire and the male and female forms of the PEP. The mean total PEP index score of the couples (female (F); 1.69 ± 0.55 and male (M); 1.65 ± 0.36) was below the average possible score. Although both males and their partners generally rated control over ejaculation (F; 57.4%, M; 61.1%) and satisfaction with sexual intercourse (F; 63%, M; 79.7%) as good/very good, they rate personal distress related to ejaculation (F; 64.8%, M; 83.4%) and interpersonal difficulty related to ejaculation (F; 81.5%, M; 92.6%) as ‘extremely/quite a lot’. As the time of using WD increased, male control over ejaculation increased (p = .019); as the marriage duration (p = .045) and ages (F; p = .012, M; p = .045) of the couples increased, their problems related to ejaculation increased. According to the results, couples who use WD experience PE-related problems, and the problems they experience vary depending on the period of WD use, marriage duration and age.     

Treatment of premature ejaculation

Premature ejaculation (PE) is the most common male sexual disorder, and it may have a profound negative impact on a man and his partner's lives. Different organizations and societies have no consensus on the definition and classifications of PE. However, most organizations and societies include in their definitions the intravaginal ejaculation latency time (IELT), the control of ejaculation, and the distress or impact of interpersonal difficulties. Evaluation procedures have been standardized in clinical studies by the development of an objective measurement of IELT (using a stopwatch) and by the introduction of patient-reported outcome (PRO) questionnaires on ejaculation control and sexual satisfaction. The identification of four different patterns of PE—lifelong, acquired, normal variant, and premature-like ejaculatory dysfunction—is critical because of different underlying pathogeneses and consequently different management approaches. The optimal treatment for PE should be individualized, based on a patient's symptoms, expectations, and underlying variant causes. Most lifelong PE patients need pharmacotherapy (possibly in combination with psychosexual counseling) as a first-line treatment because of the underlying neurobiological etiology and the impact of PE on the couple's relationship. The management of acquired PE is etiologically specific and may include pharmacotherapy for erectile function management in men with comorbid erectile dysfunction (ED). Men with natural variable PE complain of early ejaculation in situational or coincidental conditions; the ejaculation is inconsistent and occurs irregularly. Psychoeducation and reassurance are indicated for men with this type of PE. Psychotherapy or sex counseling is the first choice of treatment for men with premature-like ejaculatory dysfunction. All pharmacotherapies such as long-term selective serotonin reuptake inhibitors (SSRIs) or on-demand topical anesthetics are off-label indications, The benefits of pharmacotherapy toward improving ejaculation times should be weighed against their safety profiles. The development of the short-acting selective serotonin reuptake inhibitor (SSRI) dapoxetine hydrochloride (30 mg and 60 mg) for oral on-demand use opened a new era of PE treatment. Other potential pharmacotherapies such as tramadol, lidocaine/prilocaine spray, and phosphodiesterase inhibitors are still under development. Their safety and efficacy profiles should be further evaluated and supported by additional clinical studies.     

西酞普兰治疗早泄的临床观察

目的:探讨西酞普兰治疗早泄的临床疗效和安全性。方法:将2011年5月至2012年5月男科门诊就诊的80例早泄患者随机分为治疗组和对照组,每组40例。治疗组每天口服西酞普兰20 mg,对照组口服安慰剂,记录治疗前、治疗2周和4周后患者阴道内射精潜伏时间(IELT)和性交满意度分值。结果:治疗组治疗2、4周后IELT分别为(5.64±1.31)min和(7.12±1.56)min,均比治疗前[(0.91±0.18)min]明显延长(P均<0.01),且西酞普兰治疗4周后的IELT明显高于2周后(P<0.01);治疗组治疗2、4周后性交满意度分别为(6.1±1.3)分和(6.3±1.1)分,与治疗前[(2.5±0.8)分]相比有明显提高(P<0.01),而治疗2周和4周后性交满意度无显著性差异(P>0.05)。对照组治疗2、4周后IELT和性交满意度分别为(1.02±0.24)min、1.01±0.21 min和(3.0±1.1)分、(3.1±1.3)分,与治疗前[(0.95±0.17)min和(3.2±1.2)分]比较,均无显著性差异(P均>0.05)。结论:每天口服西酞普兰20 mg,对早泄患者IELT和性交满意度均有明显改善,西酞普兰治疗早泄具有较好的临床疗效和安全性。     

The Premature Ejaculation Prevalence and Attitudes (PEPA) survey: prevalence, comorbidities, and professional help-seeking

OBJECTIVES: This study evaluated the associated comorbidities and patient satisfaction with treatment options for premature ejaculation (PE), a common sexual dysfunction. METHODS: A comprehensive, Internet-based survey (the PE Prevalence and Attitudes [PEPA] survey) was conducted among men ages 18-70 in the United States, Germany, and Italy (n=12,133). Men were classified as having PE based on self-report of low or absent control over ejaculation, resulting in distress for them or their sexual partner or both. RESULTS: The prevalence of PE was 22.7% (24.0% in the United States, 20.3% in Germany, and 20.0% in Italy) and did not vary significantly with age among men over age 24 yr. Men with PE were more likely to self-report other sexual dysfunctions (e.g., anorgasmia, low libido, erectile dysfunction) and psychological disturbances (e.g., depression, anxiety, excessive stress) than men without PE (p<0.05 for all). Men with PE were most aware of (>70%) and most likely to have used (>50%) special positions during sex, interrupted stimulation, masturbation, and having intercourse more often than usual to manage their PE. Only 9.0% of men with PE reported having consulted a physician for the condition; 81.9% had to initiate the conversation about PE and 91.5% reported little or no improvement as a result of seeking treatment. CONCLUSION: PE is a highly prevalent sexual problem, with significant sexual and psychological comorbidities. Most men with PE do not seek assistance from their physician, and most of those who do are not satisfied with the results.     

The pharmacological treatment of premature ejaculation

Premature ejaculation (PE) is a common sexual dysfunction in men that is characterized by a short time to ejaculation, and a lack of control over ejaculation, and is associated with distress for men and their partners. Lack of knowledge about the aetiology of PE and lack of approved treatments might contribute to its under-diagnosis and under-treatment. The organic factors involved in PE are not well understood but serotonin (5-hydroxytryptamine, 5-HT) is important at the level of the central nervous system in the complex regulatory mechanisms involved in ejaculation. Selective serotonin reuptake inhibitor (SSRI) antidepressants (paroxetine, fluoxetine and sertraline) and the tricyclic antidepressant clomipramine increase ejaculatory control and delay ejaculation in men with PE, suggesting that pharmacological intervention might be useful for PE. These agents are intended for chronic dosing for treating psychiatric disorders because of their pharmacokinetic profile and pharmacodynamic activity, which might result in limitations when used for treating PE. Indeed, these properties might limit the utility of these drugs, whether administered on-demand or chronically, for the episodic treatment requirements of PE. Elevated synaptic 5-HT levels achieved with acute SSRI treatment might be self-limiting because of activation of presynaptic 5-HT(1A) autoreceptors, and chronic 5-HT(1A) autoreceptor desensitization might contribute to an increase in side-effects and withdrawal symptoms. Short-acting SSRIs such as dapoxetine, currently under development for the on-demand treatment of PE, might circumvent these limitations and offer better ejaculatory control and sexual satisfaction for men with PE. Phosphodiesterase-5 inhibitors have also been evaluated for treating PE, as have topical anaesthetics and the narcotic analgesic tramadol.     

Topical lidocaine-prilocaine spray for the treatment of premature ejaculation: a proof of concept study

Premature ejaculation (PE) is the most common sexual dysfunction in men. Since heightened sensitivity of the glans is implicated in PE, it seems reasonable that reducing this sensitivity could have a delaying effect on intravaginal ejaculation latency time (IVELT) without adversely affecting the sensation of ejaculation. We have developed a local anesthetic combination, in a metered-dose aerosol delivery system, that delivers lidocaine and prilocaine in base form without organic solvents. The drug can be easily removed prior to vaginal penetration, circumventing the need for a condom that most patients find undesirable. Herein, we report on a prospective open-label pilot study investigating the safety and efficacy of this novel delivery system for topical local anesthetic to the glans penis aimed at prolonging the IVELT in patients who self-reported having PE. This was an open-label prospective pilot study. The lidocaine-prilocaine (LP) aerosol delivered 7.5 mg lidocaine and 2.5 mg prilocaine, both in base form, per actuation. A total of 14 men who had been referred to urology clinics with the problem of PE were recruited. Consent was obtained from both subjects and their partners. Couples were asked to time their IVELT without treatment on one encounter, and then on five subsequent encounters were asked to apply the spray to the glans penis, leave on for 10-15 min, wipe off carefully before intercourse. The IVELT was timed with a stopwatch and then both partners were asked to rate their individual satisfaction relative to baseline without treatment. They were also asked to document any adverse events or comments. In all, 11 patients completed the study. The average IVELT increased from 1 min:24 s to 11 min:21 s (P=0.008) representing an average eight-fold increase. No subjects experienced a decrease in IVELT. The average satisfaction score for both subjects and partners was 1.0; on a scale where -1 was worse, 0 the same, +1 better and +2 much better. Topical LP spray, applied to the glans penis 15 min before intercourse, prolongs ejaculation time significantly and improves sexual satisfaction in both men with PE and their partners. The glandular numbness, noticed in only two cases, did not adversely affect the quality of the orgasm. Occasionally, a patient reported difficulty maintaining an erection while waiting the required 15 min between application of the spray and the initiation of intercourse.     

An evidence-based definition of lifelong premature ejaculation: report of the International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation

OBJECTIVE

To develop a contemporary, evidence‐based definition of premature ejaculation (PE).

METHODS

There are several definitions of PE; the most commonly quoted, the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders – 4th Edition – Text Revision, and other definitions of PE, are all authority‐based rather than evidence‐based, and have no support from controlled clinical and/or epidemiological studies. Thus in August 2007, the International Society for Sexual Medicine (ISSM) appointed several international experts in PE to an Ad Hoc Committee for the Definition of PE. The committee met in Amsterdam in October 2007 to evaluate the strengths and weaknesses of current definitions of PE, to critically assess the evidence in support of the constructs of ejaculatory latency, ejaculatory control, sexual satisfaction and personal/interpersonal distress, and to propose a new evidence‐based definition of PE.

RESULTS

The Committee unanimously agreed that the constructs which are necessary to define PE are rapidity of ejaculation, perceived self‐efficacy, and control and negative personal consequences from PE. The Committee proposed that lifelong PE be defined as a male sexual dysfunction characterized by ejaculation which always or nearly always occurs before or within about one minute of vaginal penetration, and the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. This definition is limited to men with lifelong PE who engage in vaginal intercourse. The panel concluded that there are insufficient published objective data to propose an evidence‐based definition of acquired PE.

CONCLUSION

The ISSM definition of lifelong PE represents the first evidence‐based definition of PE. This definition will hopefully lead to the development of new tools and patient‐reported outcome measures for diagnosing and assessing the efficacy of treatment interventions, and encourage ongoing research into the true prevalence of this disorder, and the efficacy of new pharmacological and psychological treatments.     

选择性显微阴茎背神经切断术治疗原发性早泄的临床观察

目的:评价显微镜下选择性阴茎背神经切断术治疗原发性早泄(PPE)的效果。方法:2010年9月至2012年10月,选择原发性早泄78例,行显微镜下选择性阴茎背神经切断术,切除分支5支9例,6支17例,7支15例,8支14例,9支8例,10支6例,11支6例,12支3例。术后随访12月。记录治疗前、治疗后患者阴道内射精潜伏时间(IELT)和性交满意度分值。结果:治疗前后IELT分别为(0.86±0.32)min和(6.65±3.9)min,有显著性差异(P<0.01)。治疗前后患者性交满意度分值分别为(7.32±2.52)分和(12.32±3.76)分,有显著性差异(P<0.01)。治疗前后配偶性交满意度分值分别为(4.46±1.36)分和(12.73±1.45)分,有显著性差异(P<0.01)。结论:显微镜下选择性阴茎背神经切断术治疗原发性早泄安全、有效。