Premature ejaculation: state of the art

Premature ejaculation (PE) is a frequent male sexual complaint.This occurrence does not automatically imply the existence of a male sexual disorder. The current DSM definition of PE has a low positive predictive value with a high associated risk for false-positive diagnoses of PE. A new classification in four well-defined PE syndromes has recently been proposed for the pending DSM-V. According to this new classification there are different pathophysiologies and treatments of PE, dependent on the underlying PE syndrome. Some types are particularly neurobiologically or medically determined and need drug treatment; other types, which are mainly psychologically determined, need psychotherapy or both drug treatment and psychotherapy. A meta-analysis of all selective serotonin reuptake inhibitors (SSRIs) and clomipramine studies, which were performed according to current standards of evidence-based medicine, demonstrated a similar efficacy for the daily treatment with the serotonergic antidepressants paroxetine hemihydrate, clomipramine, sertraline, and fluoxetine, with paroxetine hemihydrate exerting the strongest effect on ejaculation. On-demand treatment with SSRIs generally exerts much less ejaculation delay than daily SSRI treatment. Other on-demand treatment options are the topical use of anesthetics, tramadol, and phosphodiesterase type 5 inhibitors. Caution is needed with tramadol with regard to its potential addictive properties. There is insufficient evidence for the ejaculation delaying effects of phosphodiesterase type 5 inhibitors and intracavernous injection of vasoactive drugs.     

Premature ejaculation： current and future treatments

Premature ejaculation （PE） is recognized to be the most common male sexual disorder. PE provides difficulties for professionals who treat this condition because there is neither a universally accepted definition nor a medication approved by the Food and Drug Administration （FDA）. Despite these shortcomings, physicians continue to diagnose their patients with PE according to major guidelines and treat them with either behavioral therapies or off-label medications. This review focuses on current and emerging treatment options and medications for PE. Advantages and limitations of each treatment option are discussed in the light of current published peer-reviewed literature.     

Psychological approaches to the treatment of rapid ejaculation

This article reviews the psychological theories and treatment approaches to premature ejaculation. It also describes the potential negative psychological effect of this condition on the man and his partner. Recommendations and guidelines for providing individual and conjoint treatment with the partner are discussed as is the role of combined pharmacological and psychological intervention. The limitations of psychotherapy outcome studies are discussed and the success of psychological interventions for premature ejaculation is assessed from the studies’ data. Finally, suggestions for improving the long-term therapeutic efficacy of psychotherapy are offered. Psychological intervention remains a vital alternative in the treatment of premature ejaculation.     

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.     

Psychological factors associated with male sexual dysfunction: screening and treatment for the urologist

Male sexual dysfunctions, including erectile dysfunction, hypoactive sexual desire disorder, premature ejaculation, and delayed ejaculation, are a complex amalgam of interrelated biological, psychological, and contextual variables that can combine to produce distressing symptoms both for the male diagnosed with the dysfunction and for his partner. This article describes the assessment process for identifying the psychological concerns associated with the man's sexual complaint, and presents a stepwise algorithm for treating mild to moderate psychosocial issues. Physicians' awareness of psychological and interpersonal issues will help them better manage patients' ongoing medical treatment and limit discontinuation of efficacious therapies.     

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.     

Sexological approach to ejaculatory dysfunction

Ejaculatory disorders include premature, deficient (delayed ejaculation and anejaculation) and retrograde ejaculation. A rare symptom connected to ejaculatory disorders is male anorgasmia. In the past, ejaculatory disorders were considered as typical relational and psychological symptoms. For this reason, a number of behavioural and psycho-relational approaches have flourished from the first ideas of curing sexual problems with empirical therapy, focusing on the symptoms of sexual pathology. Such treatment includes assessment, behavioural and educational components, psychotherapy in the context of the relationship and sexual timetables. Recent advances in understanding the importance and frequency of ejaculatory disorders, insights into their organic and non-organic pathophysiology and the efficacy of a growing arsenal of pharmacological therapies lead to a new challenge which can be confronted only with the development of new, integrated therapeutic alternatives from a modern somato-psychic and holistic viewpoint.     

Rapid ejaculation: a review of nosology, prevalence and treatment

Information concerning the epidemiology, etiology and treatment of premature (rapid) ejaculation is reviewed. Evidence concerning the prevalence of premature ejaculation indicates that subjective concern about rapid ejaculation is a common concern worldwide. Hypotheses concerning the pathogenesis of premature ejaculation include: (1) that it is a learned pattern of ejaculation maintained by interpersonal anxiety, (2) that it is the result of dysfunction in central or peripheral mechanisms regulating ejaculatory thresholds and (3) that it is a normal variant in ejaculatory latency. Current evidence based treatment interventions include behavioral psychotherapy and the use of pharmacological agents, including topical anesthetic agents and selective serotonin reuptake inhibitors.     

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 neurobiological approach to premature ejaculation

PURPOSE: Data showing the neurobiological background of rapid ejaculation was reviewed. In addition, new hypotheses to integrate clinical symptomatology, psychopharmacotherapy and psychotherapy of rapid ejaculation with brain function are provided. MATERIALS AND METHODS: A computerized MEDLINE search, and manual bibliographic review of cross-references and neurobiological animal studies were performed. These reports were analyzed, summarized and compared with the studies performed by the author. RESULTS: The literature on premature ejaculation published between 1887 and 2001 was reviewed. It appeared that the various psychological hypotheses and psychotherapies have not adequately been investigated. In contrast, psychopharmacological treatment studies, animal research data and stopwatch assessments in men with rapid (premature) ejaculation indicate that lifelong rapid ejaculation is a neurobiological phenomenon related to central serotonergic neurotransmission and likely influenced by hereditary factors. CONCLUSIONS: Basic and clinical psychopharmacological studies suggest that premature ejaculation is a not a psychological disturbance but a neurobiological phenomenon.     

心理行为干预在早泄治疗中的作用

目的:探讨综合心理行为治疗对早泄(PE)患者射精潜伏期、夫妻双方对性生活满意程度的干预效果及对临床疗效的影响。方法:90例PE患者随机分为心理行为干预组和对照组,每组45例。两组均给予药物治疗,干预组同时配合综合性心理行为治疗,共6周,干预前后应用阴道内射精潜伏期及中国早泄患者性功能评价表(C IPE)、焦虑自评量表(SAS)进行评定,并比较两组临床疗效。结果:治疗前干预组和对照组阴道内射精潜伏期分别为(0.69±0.25)、(0.71±0.19)m in,治疗后分别为(5.87±0.59)、(4.76±0.54)m in,两组治疗后差值差异有显著性(P<0.01)。干预组C IPE的控制射精难易程度、患者性生活满意度、配偶性生活满意度、性生活焦虑程度评分高于对照组,两组差值差异有显著性(t=2.12,2.31,2.01,2.24,P均<0.05)。两组治疗后SAS评分差值差异有显著性(P<0.01)。治疗后1个月两组显效率分别为82.9%、30.0%。两组差值差异有显著性(P<0.01)。结论:心理行为干预可进一步改善传统药物治疗PE的疗效。     

早泄药物治疗进展

早泄是最常见的性功能障碍之一,对患者生活质量产生重要影响。多年来行为疗法在早泄治疗中占主要地位,但患者较难控制,长期效果也不满意。目前常用的治疗早泄药物包括阴茎局部用药、5型磷酸二酯酶抑制剂和5羟色胺再吸收抑制剂,但临床应用有限。开发按需使用、耐受性好、快速起效、快速清除的口服药物是今后研究的方向。现对早泄药物治疗及进展进行综述,为临床用药提供参考。     

Premature ejaculation: defining sex in the absence of context

Medical and psychiatric literature defines premature, early or rapid ejaculation from diverse perspectives and provides explanations and treatment options that reflect their historical development. Medical discourse focuses on premature ejaculation as a neuro-biological phenomenon with a growing ‘evidence’ base emerging for both defining the condition and treating it with selective serotonin re-uptake inhibitors (SSRIs).Current definitions of premature ejaculation however are difficult to deploy clinically; ‘marked interpersonal distress’ is a subjective measure and not all men are able (or willing) to time their sexual activity with a stopwatch. The addition of a defined measure of intravaginal ejaculatory latency time (IELT) is, perhaps, useful for research, but less so for the individual men with premature ejaculation. Psychiatric literature considers the diagnosis and management of premature ejaculation from a behavioural perspective, where the man learnt ‘hurriedly’ and therefore got into a pattern of hurried sexual activity, although there is no compelling data (or evidence) that adoption of behavioural therapies are successful in providing a ‘cure’ for the problem.Both medical and psychological perspectives appear based on certain assumptions, i.e. that of the construction of ‘normal’ sexual activity and function. Neither medical rationalities nor psychological perspectives consider the person who is the premature ejaculator, and both generally fail to consider his social contexts and cultural meanings or the anxieties of managing gender-determined role performances. Similarly, the ‘irrationalities’ of erotic desire, intimacy and embodiment remain largely marginal or invisible elements in the pursuit of ‘evidence’.Whilst there is little sociological literature on the topic, premature ejaculation provides an example, par excellence, of an aspect of human experience that demonstrates the paradigmatic tensions between medical positivism and the cultural constructions of experience. This paper seeks to discuss premature ejaculation from another perspective, problematising the complexities of sometimes contradictory, social, sexual and gendered identities, and reflecting on a number of key areas that seem absent from the clinical literature on premature ejaculation.     

Lifelong premature ejaculation: definition, serotonergic neurotransmission and drug treatment

The ejaculation distribution theory (EDT) postulates a biological continuum of the intravaginal ejaculation latency time (IELT) in men. Such an continuum has recently been found in two epidemiological stopwatch studies. In addition, a continuum of ejaculation latency time has also been demonstrated in laboratory rats. It is suggested that the invariable parts of ejaculation, i.e. premature and retarded ejaculation are highly influenced by genetic and neurobiological factors. In contrast, superimposed on biological roots, ejaculation of men, in the middle part of the continuum, is probably more easily influenced by environmental and psychological factors. A meta-analysis of 35 daily SSRI and clomipramine treatment studies demonstrated a similar efficacy for paroxetine, clomipramine, sertraline and fluoxetine, with paroxetine exerting the strongest effect on ejaculation. Based on fundamental insights into serotonergic neurotransmission, it is suggested that on-demand conventional SSRI treatment will not lead to similarly impressive ejaculation delay as that found after daily conventional SSRI treatment. Future studies with SSRIs with short half-lives, short T_max and high C_max should elucidate whether these pharmacokinetic properties are able to affect the pharmacodynamics of 5-HT neurons in such a way that immediate clinically relevant ejaculation delay occurs.     

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.     

A Novel Treatment of Premature Ejaculation

The investigation of the etiology and treatment of premature ejaculation (PE), a common and significant problem for men and their partners, has been limited by the lack of defined outcomes and differences in clinical trial designs. Currently, no medication has been approved for the treatment for PE worldwide. Recognition of serotonin as a key mediator in ejaculatory signaling has raised interest in the utility of pharmacologic intervention for treating PE. Selective serotonin reuptake inhibitors (SSRIs) have been used off-label for PE, with varied results. However, treatment with currently available SSRIs typically requires chronic dosing that increases drug accumulation and the attendant risk of adverse events. Dapoxetine is an SSRI with a short half-life (1.2 h), developed specifically for the treatment of men with PE. This agent has a unique pharmacokinetic profile characterized by rapid absorption and elimination. Dapoxetine is metabolized by multiple pathways, and no clinically relevant drug–drug interactions have been identified. Furthermore, dapoxetine pharmacokinetics do not appear to be affected by food, age, alcohol, or phosphodiesterase type 5 (PDE5) inhibitors to a relevant degree. In two placebo-controlled phase 3 trials involving >2600 men with PE, dapoxetine 60 mg given as needed over 12 wk significantly prolonged the stopwatch-assessed intravaginal ejaculatory latency time (IELT) from 0.91 min at baseline to 3.32 min (p < 0.0001), increased control over ejaculation, and increased sexual satisfaction for men and their partners compared with placebo (both p < 0.0001). These results suggest that dapoxetine may meet the medical need for on-demand therapy for PE.     

Impact of treatment of BPH on sexuality

Benign prostatic hyperplasia (BPH) can have a profound affect on a patient's quality of life and sexual function and is considered by patients to be one of the most important aspects affected by the disease. Different treatments can produce a variable response in terms of the patient's quality of life, including sexual activity and satisfaction. Varying rates of erectile dysfunction (ED) and retrograde ejaculation following surgery for BPH have been reported. In general, the incidence of these side-effects is less after minimally invasive therapies, such as interstitial laser coagulation and transurethral microwave therapy, but the data available are limited. The lowest rates of sexual dysfunction are reported with medical therapies. The 5alpha-reductase inhibitor, finasteride, can result in ED in 5-9% of patients and ejaculation disorders in 0.8-2.0%. With the exception of tamsulosin, alpha(1) blockers are associated with a low rate of sexual dysfunction. No cases of ED have been reported with alfuzosin and abnormal ejaculation with terazosin or alfuzosin is negligible. Indeed, early research suggests a beneficial effect of alpha(1) blockers on sexual function. In addition to information on the efficacy of a particular therapy, patients should be informed of side effects, in particular those relating to sexual function, in order that they can make informed treatment decisions.Prostate Cancer and Prostatic Diseases (2001) 4, S12-S16     

Dapoxetine and the treatment of premature ejaculation

Background

Premature ejaculation (PE) is the most common male sexual complaint. Off-label oral selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of PE. Dapoxetine is a short-acting SSRI specifically designed for on-demand use. The objective of this communication is to summarize the clinical and physiological evidence regarding the role of the serotonergic pathway and specifically dapoxetine in the treatment of PE.

Methods

A PubMed search was conducted on articles reporting data on dapoxetine for the treatment of PE. Articles describing the pathophysiology and treatment options for PE were additionally included for review.

Results

The etiology of PE is multi-factorial in nature. There are many treatment options for PE such as psychological/behavioral therapy, topical anesthetic agents, phosphodiesterase type 5 (PDE-5) inhibitors, and tramadol hydrochloride. SSRIs play a major role in PE treatment. Animal and clinical studies in addition to its pharmacokinetic document dapoxetine’s clinical efficacy and safety for on-demand treatment of PE.

Conclusions

Dapoxetine demonstrates clinical efficacy and a favorable side effect profile. Dapoxetine is currently the oral drug of choice for on-demand treatment of PE.     

团体叙事心理干预对青少年抑郁症患者的影响

目的 探讨团体叙事心理干预对改善青少年抑郁症患者的效果。方法 将2021年12月至2022年2月收治的51例青少年抑郁症患者分为对照组，2022年3～5月收治的51例青少年抑郁症患者分为干预组，对照组行常规心理护理，干预组在常规心理护理基础上实施团体叙事心理干预，内容包括成立团体叙事心理干预小组、确定团体叙事活动目标、评估患者个人心理状态、制订并实施团体叙事心理干预方案。干预后评价两组抑郁焦虑情绪。结果 两组干预后1个月、3个月、4个月抑郁、焦虑评分比较，差异有统计学意义（均P＜0.05）。结论 团体叙事心理干预可有效改善青少年抑郁症患者抑郁焦虑情绪，促进其回归家庭社会。     

盐酸曲马多联合行为疗法治疗早泄的安全性、有效性临床观察

目的:评价盐酸曲马多联合行为疗法治疗早泄的安全性、有效性。方法:按随机原则将72例早泄患者分为治疗组和对照组,治疗组(n=36)性生活前2 h口服盐酸曲马多50 mg联合行为疗法,对照组(n=36)予以单纯行为疗法,两组疗程均为8周,记录治疗前后阴道内射精潜伏期(IELT)、配偶性生活满意度评分、临床总有效率、不良反应和肝、肾功能。结果:两组治疗前后在IELT和改善配偶性交满意度评分方面有显著性差异(P<0.01),两组治疗效果的总有效率,治疗组为72.2%,对照组为47.2%,治疗组较对照组治疗后IELT、改善配偶性交满意度评分和临床总有效率方面有显著性差异(P<0.05),10例(27.8%)患者出现不良反应,治疗组治疗前后肝肾功能无统计学差异(P>0.05)。结论:盐酸曲马多联合行为疗法在延长IELT及改善配偶性交满意度评分、临床总有效率和肝、肾功能方面,其安全性和有效性值得肯定。但盐酸曲马多为阿片类药物,成瘾性还有待评估,是否作为国内治疗早泄的常规治疗药物尚需进行多中心、双盲临床安全性及有效性的进一步研究。