Chris G. McMahon

Ejaculatory dysfunction is a common complaint and is often associated with a reduced quality of life for sufferer and partner. The spectrum of ejaculatory dysfunction extends from premature ejaculation (PE) to delayed ejaculation (DE) and anejaculation. Over the past 20–30 years, thePEtreatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Multiple well‐controlled, evidence‐based studies have demonstrated the efficacy and safety of selective serotonin re‐uptake inhibitors in delaying ejaculation, confirming their role as first‐line agents for the treatment of lifelong and acquiredPE. More recently, there has been increased attention to the psychosocial consequences ofPE, its epidemiology, its aetiology and its pathophysiology by both clinicians and the pharmaceutical industry.DEand anejaculation are probably the least common, least studied and least understood of the male sexual dysfunctions. However, their impact is significant as they may result in a lack of sexual fulfilment for both the man and his partner, an effect further compounded when procreation is among the couple's goals of sexual intercourse. The causes ofDE, anejaculation and anorgasmia are manifold. Numerous psychotherapeutic treatments are described for the management of delayed or anejaculation. Although some appear to be effective, none has been properly evaluated in large‐scale samples. Treatment ofDEor anejaculation with pharmacotherapy has met with limited success. No drugs have been approved by regulatory agencies for this purpose, and most drugs that have been identified for potential use have limited efficacy, impart significant side‐effects or are yet considered experimental in nature.

In the past 30 years, advances in basic science have been instrumental in the evolution of the male sexual health treatment paradigm from a psychosexual model to a new model, which includes oral and intracavernosal injection pharmacotherapy, vacuum constriction devices and penile prostheses for the treatment of erectile dysfunction. This progress has coincided with an increased understanding of the nature of male sexual health problems, and epidemiological data that confirm that these problems are widely prevalent and the source of considerable morbidity, both for individuals and within relationships.

Men with comorbid erectile dysfunction (ED) and premature ejaculation (PE) may be concomitantly prescribed a phosphodiesterase type 5 (PDE5) inhibitor and dapoxetine. Evaluate efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE and ED who were being treated with PDE5 inhibitors. This randomized, double-blind, placebo-controlled, flexible-dose, multicenter study enrolled men ≥18 years who met diagnostic criteria for PE including intravaginal ejaculatory latency time (IELT) of ≤2 minutes in ≥75% of sexual intercourse episodes; were on stable regimen of a PDE5 inhibitor; and had International Index of Erectile Function-erectile function domain score ≥21. Subjects received placebo, dapoxetine 30 mg, or dapoxetine 60 mg prn (1–3 hours before intercourse) for 12 weeks. Stopwatch-measured average IELT, Clinical Global Impression of Change (CGIC) in PE, Premature Ejaculation Profile (PEP), and treatment-emergent adverse events (TEAEs). Of 495 subjects randomized, 429 completed the study. Arithmetic mean average IELT significantly increased with dapoxetine vs. placebo at end point (5.2 vs. 3.4 minutes) and weeks 4, 8, and 12 (P ≤ 0.002 for all). Men who described their PE at least “better” using the CGIC were significantly greater with dapoxetine vs. placebo at end point (56.5% vs. 35.4%) and weeks 4, 8, and 12 (P ≤ 0.001 for all). Significantly better outcomes were also reported with dapoxetine vs. placebo on PEP measures. Incidence of TEAEs was 20.0% and 29.6% in placebo- and dapoxetine-treated subjects, respectively (P = 0.0135). TEAEs led to discontinuation in 1.6% of subjects in both groups. Most frequent TEAEs were known adverse drug reactions of dapoxetine treatment including nausea (9.2%), headache (4.4%), diarrhea (3.6%), dizziness (2.4%), and dizziness postural (2.4%). In men with PE and comorbid ED on a stable regimen of PDE5 inhibitor, dapoxetine provided meaningful treatment benefit and was generally well tolerated. McMahon CG, Giuliano F, Dean J, Hellstrom WJG, Bull S, Tesfaye F, Sharma O, Rivas DA, and Aquilina JW. Efficacy and safety of dapoxetine in men with premature ejaculation and concomitant erectile dysfunction treated with a phosphodiesterase type 5 inhibitor: Randomized, placebo-controlled, phase III study. J Sex Med 2013;10:2312–2325.

Ejaculatory/orgasmic disorders are common male sexual dysfunctions and include premature ejaculation (PE), inhibited ejaculation, anejaculation, retrograde ejaculation, and anorgasmia. To provide recommendations and guidelines of the current state-of-the-art knowledge for management of ejaculation/orgasmic disorders in men as standard operating procedures (SOPs) for the treating health care professional. The International Society of Sexual Medicine Standards Committee assembled over 30 multidisciplinary experts to establish SOPs for various male and female sexual medicine topics. The SOP for the management of disorders of orgasm and ejaculation represents the opinion of four experts from four countries developed in a process over a 2-year period. Expert opinion was based on grading of evidence-based medical literature, limited expert opinion, widespread internal committee discussion, public presentation, and debate. PE management is largely dependent upon etiology. Lifelong PE is best managed with PE pharmacotherapy (selective serotonin reuptake inhibitors and/or topical anesthetics). The management of acquired PE is etiology specific and may include erectile dysfunction (ED) pharmacotherapy in men with comorbid ED. All men seeking treatment for PE should receive basic psychosexual education. Graded behavioral therapy is indicated when psychogenic or relationship factors are present and is often best combined with PE pharmacotherapy in an integrated treatment program. Delayed ejaculation, anejaculation, and/or anorgasmia may have a biogenic and/or psychogenic etiology. Men with age-related penile hypoanesthesia should be educated, reassured, and instructed in revised sexual techniques which maximize arousal. Retrograde ejaculation is managed by education, patient reassurance, and pharmacotherapy. Additional research is required to further the understanding of the disorders of ejaculation and orgasm. McMahon CG, Jannini E, Waldinger M, and Rowland D. Standard operating procedures in the disorders of orgasm and ejaculation. J Sex Med **;**:**–**.

Premature ejaculation (PE) is a common male sexual disorder which is associated with substantial personal and interpersonal negative psychological consequences. Pharmacotherapy of PE with off-label antidepressant selective serotonin reuptake inhibitors (SSRIs) is common, effective and safe. Development and regulatory approval of drugs specifically for the treatment of PE will reduce reliance on off-label treatments and serve to fill an unmet treatment need. The objective of this article is to review evidence supporting the efficacy and safety of dapoxetine in the treatment of PE. MEDLINE, Web of Science, PICA, EMBASE and the proceedings of major international and regional scientific meetings were searched for publications or abstracts published during the period 1993–2012 that used the word ‘dapoxetine’ in the title, abstract or keywords. This search was then manually cross referenced for all papers. This review encompasses studies of dapoxetine pharmacokinetics, animal studies, human phase I, II and III studies, independent postmarketing and pharmacovigilance efficacy and safety studies and drug-interaction studies. Dapoxetine is a potent SSRI which is administered on demand 1–3 h prior to planned sexual contact. It is rapidly absorbed and eliminated, resulting in minimal accumulation, and has dose-proportional pharmacokinetics which are unaffected by multiple dosing. Dapoxetine 30 mg and 60 mg has been evaluated in five industry-sponsored randomized, double-blind, placebo-controlled studies in 6081 men aged at least 18 years. Outcome measures included stopwatch-measured intravaginal ejaculatory latency time (IELT), Premature Ejaculation Profile (PEP) inventory items, Clinical Global Impression of Change (CGIC) in PE, and adverse events. Mean IELT, all PEP items and CGIC improved significantly with both doses of dapoxetine versus placebo (all p <0.001). The most common treatment-related adverse effects included nausea (11.0% for 30 mg, 22.2% for 60 mg), dizziness (5.9% for 30 mg, 10.9% for 60 mg), and headache (5.6% for 30 mg, 8.8% for 60 mg), and evaluation of validated rated scales demonstrated no SSRI class-related effects with dapoxetine use. Dapoxetine, as the first drug developed for PE, is an effective and safe treatment for PE and represents a major advance in sexual medicine.

Introduction Premature ejaculation (PE) is a common male sexual dysfunction. The prevalence of PE in the Asia‐Pacific region has not been comprehensively studied. Aim The aim of this study is to evaluate PE prevalence in nine Asia‐Pacific countries and the impact of PE on sufferers. Methods A random sample of heterosexual males aged 18–65 years in a stable sexual relationship currently or in the past 2 years completed a 48‐question survey by computer‐assisted interviewing, online, or in‐person; the survey and recruitment methodologies varied by location. The survey included demographic questions, the five‐question Premature Ejaculation Diagnostic Tool (PEDT), the five‐question Sexual Health Inventory for Men (SHIM), and the 10‐question Index of Premature Ejaculation (IPE). Separately, men self‐reported having PE (lifelong or acquired) or erectile dysfunction (ED). Main Outcome Measures The PEDT was used to diagnose PE or probable PE; the SHIM was used to diagnose ED; and the IPE was used to assess respondent's attitudes toward PE. Results Of the 4,997 men who completed the survey, the prevalences of PEDT‐diagnosed PE, PEDT‐diagnosed probable PE, and self‐reported PE were 16%, 15%, and 13%, respectively. Less than half of men with PEDT‐diagnosed PE (N = 816) or probable PE (N = 738) self‐reported the condition (40% and 19%, respectively), and 6% of men with a PEDT diagnosis of no PE self‐reported PE. In contrast, more respondents self‐reported ED (8%) than had SHIM‐diagnosed moderate or severe ED (5%). IPE responses indicated that 45%, 46%, and 23% of men with PEDT‐diagnosed PE were somewhat or very dissatisfied with the length of intercourse before ejaculation, their control over ejaculation, and with sexual intercourse, respectively. Conclusions. In this study, PE was more prevalent than ED in the Asia‐Pacific countries surveyed, but only 40% of men with PEDT‐diagnosed PE self‐reported PE. McMahon CG, Lee G, Park JK, and Adaikan PG. Premature ejaculation and erectile dysfunction prevalence and attitudes in the Asia‐Pacific region. J Sex Med 2012;9:454–465.

Introduction: New diagnostic criteria for lifelong premature ejaculation (PE) have been proposed by the International Society of Sexual Medicine (ISSM), including an intravaginal ejaculatory latency time (IELT) of less than about 1 minute, lack of control over ejaculation, and PE-related distress or bother. Aim: The aim of this study was to review evidence supporting the efficacy and safety of oral agents for the treatment of PE in the context of the new ISSM criteria. Methods: The PubMed database was searched for randomized, double-blind, placebo-controlled studies of oral agents in PE that included stopwatch measurements of IELT. Main Outcome Measures: The main outcome measure used for this study was a review of the efficacy and safety data of oral agents for PE aligned with ISSM criteria. Results: Since the latest meta-analyses using similar criteria (conducted in 2004 and 2005 for selective serotonin reuptake inhibitors [SSRIs] and phosphodiesterase type 5 [PDE-5] inhibitors, respectively), eight studies evaluated SSRIs vs. placebo, one compared SSRIs, two evaluated PDE-5 inhibitors, and one evaluated an SSRI/PDE-5 inhibitor combination. New agents included dapoxetine (five studies) and tramadol (one study). Six studies enrolled men who met an approximation of the ISSM criteria. Although evidence suggests that most SSRIs, tramadol, and dapoxetine increase IELT to varying degrees, few studies included control over ejaculation and PE-related distress or bother as enrollment criteria or used validated patient-reported outcome instruments to evaluate these parameters. Among studies that provided comprehensive adverse event data, safety and tolerability observations in men with PE were generally similar to those observed in other populations; however, with the exception of dapoxetine, known SSRI-class effects (e.g., withdrawal syndrome) were not evaluated in men with PE. Conclusions: This systematic review of well-controlled clinical trials in PE has demonstrated that while many oral agents, particularly SSRIs, tramadol, and dapoxetine, have proven effective and safe for the treatment of men with PE, few have been evaluated for their effects on the specific elements of the ISSM criteria.