The link between penile hypersensitivity and premature ejaculation

Study Type – Aetiology (case control)
Level of Evidence 3b What’s known on the subject? and What does the study add? Very little is known about the aetiology of premature ejaculation. This analysis shows that many PE patients have a heightened penile sensitivity. This information could result in the design and development of new drugs.

OBJECTIVES

To investigate the correlation between penile hypersensitivity and premature ejaculation (PE), as defined by the criteria identified by the International Society of Sexual Medicine (ISSM). Penile hypersensitivity as a cause of PE is based on historical clinical neurophysiological data and clinical efficacy of the topical desensitizing agent PSD502 in the treatment of PE. PSD502 is a eutectic‐like mixture of two local anaesthetics, lidocaine and prilocaine, whose primary action is to reduce neuronal conduction in sensory afferents.

METHODS

Historical neurophysiological data was reviewed, together with data from the recent PSD502 clinical trials, including the first published double‐blind clinical trial data evaluating a topical desensitizing agent in a population of men with PE, as per the new ISSM definition. The clinical profile of PSD502, based on its local anaesthetic properties, is used as a surrogate index of the role of sensory afferents in the ejaculatory reflex.

RESULTS

The published data does not support unequivocally penile hypersensitivity as the cause of PE. Interpretation of the data is hampered by the variability of the populations described as having PE across studies. Data from the PSD502 clinical trials clearly shows that PSD502 increases ejaculatory latency, and improves control and sexual satisfaction when applied topically to men with PE 5 min before intercourse, enabling subjects to delay ejaculation up to six times longer than those who used a placebo.

CONCLUSION

The clinical profile of PSD502 lends credibility to the penile hypersensitivity hypothesis for PE. The predominant action of local anaesthetics is to reduce neuronal firing in sensory afferents; the clinical profile of PSD502, which shows improvement of ejaculatory function in the absence of a generalized reduction in penile sensitivity, can most readily be explained based on an underlying hypersensitivity in patients with PE.     

Genetic and environmental effects on the continuity of ejaculatory dysfunction

Study Type – Symptom prevalence (retrospective cohort)
Level of Evidence 2b

OBJECTIVES

To investigate temporal continuity in ejaculatory dysfunction by comparing self‐reported experiences of premature ejaculation (PE) at first intercourse with self‐reported PE and delayed ejaculation at present, and to clarify whether and to what extent genetic or environmental factors affect continuity in ejaculatory dysfunction, as previous studies indicate moderate heritability for PE at first intercourse.

SUBJECTS AND METHODS

The study comprised retrospective self‐reported data on ejaculatory performance at first sexual intercourse and a concurrent self‐report of the same at the time of data collection in a population‐based sample of 2633 Finnish twins and their siblings aged 18–48 years (mean 26.63, sd 4.68). The continuity of ejaculatory function was assessed by correlation and multiple regression. Reasons for continuity were separated into genetic and environmental sources using twin‐model fitting.

RESULTS

Ejaculatory function, particularly PE, was stable over time. Genetic effects accounted for ≈30% of the variance in PE both at first intercourse and when measured at data collection. Unshared environmental effects accounted for most of the variance (≈70%). Genetic effects were almost identical between the sample occasions, but there was a substantial discrepancy between unshared environmental effects affecting PE at first intercourse and unshared environmental effects affecting PE later in life. Age effects were generally negligible. Data were self‐reported and retrospective, and thus vulnerable to response bias.

CONCLUSIONS

Ejaculatory dysfunction seems to be temporally stable both in the short and long term. Genes that contribute to the variance in PE at first intercourse are similar to those that contribute to the variance in PE later in life, whereas there are, in this regard, substantial differences in the unshared environmental factors that are a cause of 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 relationship between female sexual function index domains and premature ejaculation

Purpose

The aim of this prospective, observational study was to investigate the relationship between premature ejaculation (PE) and female sexual response cycle, using the female sexual function index (FSFI). The FSFI evaluates female sexual function in six domains: desire, arousal, lubrication, orgasm, satisfaction, and pain.

Methods

All men were considered to have PE if they fulfilled the criteria of the second Ad Hoc International Society for Sexual Medicine (ISSM) Committee. All men were also assessed by the Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculatory latency time (IELT) using stopwatch which was held by the partner. All women completed the FSFI.

Results

A total of 181 couples who had regular sexual intercourse with one partner for the past 6 months were enrolled the study. By the definition of ISSM Committee, there were 117 men with PE and 64 men without PE. Partners of men with PE had significantly lower total FSFI scores than did partners of men without PE (21.8?±?3.5 for PE and 26.4?±?3.1 for non-PE, p?<?0.001). Moreover, all the domains of the FSFI scoring system were separately associated with PE. According to the mean FSFI scores, the 48.43% of women had sexual dysfunction in the non-PE group, and all women had sexual dysfunction in PE group.

Conclusion

PE is associated with female sexual dysfunction and all of the female sexual dysfunction domains, as determined by FSFI scores.

     

New insights on premature ejaculation: a review of definition,classification, prevalence and treatment

There are ongoing debates about the definition, classification and prevalence of premature ejaculation (PE). The first evidence-based definition of PE was limited to heterosexual men with lifelong PE who engage in vaginal intercourse. Unfortunately, many patients with the complaint of PE do not meet these criteria. However, these men can be diagnosed as one of the PE subtypes, namely acquired PE, natural variable PE or premature-like ejaculatory dysfunction. Nevertheless, the validity of these subtypes has not yet been supported by evidence. The absence of a universally accepted PE definition and lack of standards for data acquisition have resulted in prevalence studies that have reported conflicting rates. The very high prevalence of 20%–30% is probably due to the vague terminology used in the definitions at the time when such surveys were conducted. Although many men may complain of PE when questioned for a population-based prevalence study, only a few of them will actively seek treatment for their complaint, even though most of these patients would define symptoms congruent with PE. The complaints of acquired PE patients may be more severe, whereas complaints of patients experiencing premature-like ejaculatory dysfunction seem to be least severe among men with various forms of PE. Although numerous treatment modalities have been proposed for management of PE, only antidepressants and topical anaesthetic creams have currently been proven to be effective. However, as none of the treatment modalities have been approved by the regulatory agencies, further studies must be carried to develop a beneficial treatment strategy for PE.     

The effects of three phosphodiesterase type 5 inhibitors on ejaculation latency time in lifelong premature ejaculators: a double-blind laboratory setting study

Study Type – Therapy (RCT)
Level of Evidence 1b What’s known on the subject? and What does the study add? Several authors have reported their experience with PDE5 inhibitors alone or in combination with selective serotonin re‐uptake inhibitors for treating premature ejaculation. However, to our knowledge, this is the first laboratory design study to evaluate the effects of three PDE5 inhibitors throughout the ejaculation process in men with lifelong premature ejaculation. In this laboratory setting study PDE5 inhibitors seem to prolong ELT but the difference from placebo is significant only in vardenafil. The quality of penile rigidity is better with PDE5 inhibitors in the post‐ejaculatory period but the difference is significant only in sildenafil and vardenafil.

OBJECTIVE

? To evaluate the effects of three phosphodiesterase type 5 (PDE5) inhibitors on the ejaculation process in men with lifelong premature ejaculation using a double‐blind laboratory setting.

PATIENTS AND METHODS

? Eighty men with lifelong premature ejaculation, 20 in each group, received placebo, vardenafil (10 mg), sildenafil (50 mg) or tadalafil (20 mg) in a double‐blind study design. Placebo or PDE5 inhibitor was ingested after at least 2 h fasting and non‐smoking. The subjects were placed in a silent room immediately and real‐time penile rigidity and tumescence was monitored. ? Subjects read some magazines or newspapers without any sexually stimulating material for 1.5 h. At the end of this period audiovisual sexual stimulation began with a video film and after the 8th minute the subject began vibratory stimulation to the frenular area. ? At the beginning of ejaculation the patient stopped stimulation. When the patient began and stopped stimulation, the light near the observer turned on and off and the observer calculated the ejaculation period with a chronometer. The elapsed time was the ejaculation latency time (ELT) in seconds. ? There was no interaction between subjects and observer during the test. The ELT, and the qualities of base and tip rigidities during ELT and after ejaculation were calculated.

RESULTS

? Median age of patients was 29 (range 22–39) years and median duration of premature ejaculation was 60 (range 7–180) months and there was no significant difference between groups. Median duration of vibratory stimulation (ELT) of subjects who received placebo was 48.5 s: 53.5 s for sildenafil, 70.0 s for tadalafil and 82.5 s for vardenafil. Compared with the placebo group, ELT was significantly longer only in subjects receiving vardenafil (P = 0.019). ? In the post‐ejaculatory refractory period, times to last recorded base rigidities were significantly longer than placebo in vardenafil and sildenafil groups with better erection quality (P < 0.01 for each).

CONCLUSIONS

? The PDE5 inhibitors seem to prolong ELT and the quality of penile rigidity is better with PDE5 inhibitors in post‐ejaculatory period. ? These findings suggest that PDE5 inhibitors might have some beneficial effects in men with lifelong premature ejaculation.     

Identifying constructs and criteria for the diagnosis of premature ejaculation: implication for making errors of classification

OBJECTIVES

To review the many definitions of premature ejaculation (PE), determine the essential elements that best define PE, and examine and discuss the consequences of errors of inclusion and exclusion in the diagnosis of PE.

METHODS

We reviewed recent evidenced‐based studies that delineate the variables that best define PE, and the relationships between these factors. We then assessed the consequences of errors of measurement, inclusion and exclusion for setting the thresholds for the three variables.

RESULTS

PE can best be defined by a multidimensional set of criteria composed of three essential elements: (i) intravaginal ejaculatory latency time (IELT); (ii) a lack of perceived self‐efficacy or control about the timing of ejaculation; and (iii) distress and interpersonal difficulty related to the ejaculatory dysfunction. After delineating the variables, thresholds for each variable need to be determined. Carefully constructed thresholds attempt to minimize errors of inclusion and exclusion. However, even the best criteria cannot eliminate all error. The two types of errors in classification are, to some extent, inversely related: the more restrictive the criteria, the more likely that there will be errors of exclusion, whereas the more lenient the criteria the more likely there will be errors of inclusion.

CONCLUSION

Research and treatment protocols might use different threshold values for classification, as their goals might be different. For a PE research protocol, we suggest erring on the side of a more narrow definition as it would: (i) provide a more conservative, and we think, realistic prevalence of the disorder; (ii) help to establish PE as a bona fide sexual dysfunction rather than a ‘life‐style’ issue for men seeking to enhance their sexual life; (iii) ensure greater confidence in the efficacy of existing and new treatment approaches; and (iv) strengthen the likelihood of acceptance by the regulatory authorities. Conversely, standard treatment protocols for PE might use more lenient criteria if the treatment has minimal adverse events and the degree of distress of the sufferer is high.     

早泄诊断和治疗

早泄(premature ejaculation,PE)是临床上最常见的主诉之一,其共同特征为:射精潜伏期缩短、延迟或控制射精的能力下降、并引起患者痛苦/烦恼。目前尚无一致公认的PE定义。不同定义之间争论的焦点是如何设定射精潜伏期(intravaginal ejaculatory latency time,IELT)。新的分类方法将PE分为:原发性、继发性、自然变异性和早泄样射精障碍。不同类型PE发生的病理生理和病因学不同,决定了治疗方案的差异。     

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.     

The need for a revival of psychoanalytic investigations into premature ejaculation

Although psychoanalysis was the first-choice treatment for premature ejaculation (PE) between 1920 and 1960, hardly any reports on its efficacy have been published. Moreover, a scientific debate about its findings has never been fully developed. The recent progress that has been made in the classification of three different PE syndromes creates a new opportunity for psychoanalytic investigations of men with complaints of PE, distinguished by the actual duration of their intravaginal ejaculation latency time (IELT). The term premature-like ejaculatory dysfunction has been introduced to distinguish men with self-perceived PE at normal and long IELT durations from those men with lifelong, acquired and normal variable PE. Psychoanalytic research may contribute to a better understanding of the consequences of objective early ejaculations on the unconscious mental life of men with the four forms of PE. By integrating neurobiological, clinical and epidemiological data of ejaculatory performance, a revival of psychoanalytic research of PE in the four distinct, classified PE groups, will probably contribute to a deeper insight in to the unconscious mental life of men affected by PE.     

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.     

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.     

Guidelines on Male Sexual Dysfunction: Erectile Dysfunction and Premature Ejaculation

Context

Erectile dysfunction (ED) and premature ejaculation (PE) are the two most prevalent male sexual dysfunctions.

Objective

To present the updated version of 2009 European Association of Urology (EAU) guidelines on ED and PE.

Evidence acquisition

A systematic review of the recent literature on the epidemiology, diagnosis, and treatment of ED and PE was performed. Levels of evidence and grades of recommendation were assigned.

Evidence synthesis

ED is highly prevalent, and 5–20% of men have moderate to severe ED. ED shares common risk factors with cardiovascular disease. Diagnosis is based on medical and sexual history, including validated questionnaires. Physical examination and laboratory testing must be tailored to the patient's complaints and risk factors. Treatment is based on phosphodiesterase type 5 inhibitors (PDE5-Is), including sildenafil, tadalafil, and vardenafil. PDE5-Is have high efficacy and safety rates, even in difficult-to-treat populations such as patients with diabetes mellitus. Treatment options for patients who do not respond to PDE5-Is or for whom PDE5-Is are contraindicated include intracavernous injections, intraurethral alprostadil, vacuum constriction devices, or implantation of a penile prosthesis.PE has prevalence rates of 20–30%. PE may be classified as lifelong (primary) or acquired (secondary). Diagnosis is based on medical and sexual history assessing intravaginal ejaculatory latency time, perceived control, distress, and interpersonal difficulty related to the ejaculatory dysfunction. Physical examination and laboratory testing may be needed in selected patients only.Pharmacotherapy is the basis of treatment in lifelong PE, including daily dosing of selective serotonin reuptake inhibitors and topical anaesthetics. Dapoxetine is the only drug approved for the on-demand treatment of PE in Europe. Behavioural techniques may be efficacious as a monotherapy or in combination with pharmacotherapy. Recurrence is likely to occur after treatment withdrawal.

Conclusions

These EAU guidelines summarise the present information on ED and PE. The extended version of the guidelines is available at the EAU Web site (http://www.uroweb.org/nc/professional-resources/guidelines/online/).     

The etiology and management of premature ejaculation

Premature ejaculation (PE) is a common male sexual disorder. Normative data suggest that men with an intravaginal ejaculatory latency time of less than 1 min have 'definite' premature ejaculation, while men with intravaginal ejaculatory latency times of between 1 and 1.5 min have 'probable' premature ejaculation. Although there is insufficient empirical evidence to identify the etiology of PE, there is correlational evidence to suggest that men with PE have high levels of sexual anxiety and altered sensitivity of central 5-hydroxytryptamine receptors. Pharmacological modulation of the ejaculatory threshold using daily or on-demand selective serotonin reuptake inhibitors offers patients a high likelihood of achieving improved ejaculatory control within a few days of initiating treatment, leads to improvements in sexual desire and other sexual domains, and is well tolerated.     

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.     

Deleterious effects of selective serotonin reuptake inhibitor treatment on semen parameters in patients with lifelong premature ejaculation

Premature ejaculation (PE), the most common sexual dysfunctions in men, is characterized by loss or absence of ejaculatory control. PE can be classified as either a lifelong or acquired condition. Although the prevalence of lifelong PE is rather low in the general male population, recent studies demonstrated that the patients who seek treatment for their rapid ejaculation mostly report lifelong PE. Although no drug for PE has been approved by regulatory bodies, chronic selective serotonin reuptake inhibitors (SSRIs) proved to be effective in treating lifelong PE. Despite the rising use and known effects of antidepressants on ejaculation, only a few reports have evaluated the impact of these drugs on the male fertility. Thus, the aim of this review is to evaluate the efficacy and adverse effects of SSRIs on semen parameters of patients with lifelong PE as well as to assess the safety of this treatment among sexually active couples who desire to have a child.     

Novel methods for the diagnosis and treatment of ejaculatory duct obstruction

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVES

? To investigate a new method of vas deferens radiography for ejaculatory duct obstruction (EDO). ? To evaluate the effect of a procedure involving dilation of the ejaculatory duct by F9 seminal vesicoscopy.

PATIENTS AND METHODS

? Twenty‐two patients with EDO were diagnosed using semen analysis, semen fructose measurement, transrectal ultrasonography (TRUS) and vas deferens radiography. ? Of these, 18 patients were successfully treated by dilation of ejaculatory duct using F9 seminal vesicoscopy and four patients, whose treatment was unsuccessful, were treated by transurethral resection of the ejaculatory ducts (TURED). ? All patients were followed up for at least 3 months after treatment.

RESULTS

? Semen analyses in all 22 patients showed oligoasthenozoospermia or azoospermia, low semen volume (0–1.9 mL), low pH level (5.6–7.0) and absent or low semen fructose. TRUS and radiography showed pure dilated seminal vesicles on both sides in three patients, partial dilated seminal vesicles in one patient, dilation of both the ejaculatory duct and seminal vesicles in ten patients, dilated seminal vesicles and a prostatic cyst in four patients, and dilated ejaculatory duct or cystic lesions without dilated seminal vesicles in the remaining four patients. ? At >3‐month follow‐up after dilation or TURED, the semen characteristics of 18 patients were improved and sperm were present in the semen in 13 cases. Normal semen analyses were found in 7 patients and 6 patients had conceived. ? Voiding urethral radiography showed that no patients who had undergone dilation by seminal vesicoscopy had urine reflux into the ejaculatory duct. Only one patient showed urine reflux into the seminal vesicle after TURED. ? All patients felt that their symptoms had improved after treatment.

CONCLUSIONS

? The approach to vas deferens radiography using vas deferens aspiration has proved to be an effective and safe method for EDO diagnosis. ? The procedure involving the dilation of the ejaculatory duct using F9 seminal vesicoscopy is equally effective but has fewer postoperative complications than TURED.     

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.     

On‐demand d‐modafinil may be an effective treatment option for lifelong premature ejaculation: a case report

Premature ejaculation (PE) is considered to be the most common form of male sexual dysfunction. Given that acute oral administration of d‐isomer of modafinil (d‐modafinil) can extend the latency to ejaculation in rats without suppressing sexual behaviour, the effects of on‐demand d‐modafinil treatment were examined on a 30‐year‐old male patient with lifelong PE. The patient was instructed to take d‐modafinil 100 mg 3 h prior to the sexual relation for four times and was invited for a control visit. The patient was re‐evaluated 2 weeks later. He reported that his IELT increased to 15 min. He reported heartburn and insomnia when he used d‐modafinil for the first time; however, these symptoms were transient and did not recur after the initial dose. Overall, he reported considerable improvement and noted that he feels much better with the treatment. Based on this limited data, on‐demand d‐modafinil seems to be an effective treatment for men with lifelong PE. The side effects were transient and mild in the reported case. Further randomised clinical trials are necessary to elucidate the therapeutic concept of this drug in patients with lifelong PE.     

Global perspectives on the three criteria for premature ejaculation: An observational study of ejaculatory latency,ejaculatory control and bother/distress

Criteria for premature ejaculation (PE) were established using Western-based samples, yet these criteria are applied worldwide for its diagnosis. This study (a) determined whether men from various world regions differ/agree on their views of ejaculation latency (ELT) and their perceptions of ejaculatory control and bother/distress, the three criteria for PE, and (b) compared PE and non-PE men across worldwide regions on these measures. 1,065 participants were recruited via social media to respond to a survey about men's typical, ideal and PE ELTs, about their own ELT, and about perceptions of ejaculatory control and bother/distress related to PE. Responses from men from four worldwide regions were compared to a reference group of North American/European men, and PE men were compared with non-PE men across three world regions. Results showed that most world region groups showed similarity in ELT estimations. The Sub-Saharan group focused more heavily on the importance of ejaculatory control. Both ELT and ejaculatory control differed between PE and non-PE groups in all regions assessed. In conclusion, perceived ELTs and ejaculatory control show substantial consistency across world regions despite geo-cultural variations and traditions. Such findings argue for the universality of the concepts of ELT, control and bother/distress related to PE.