Disorders of Ejaculation: An AUA/SMSNA Guideline.

PURPOSE: Men who ejaculate before or shortly after penetration, without a sense of control, and who experience distress related to this condition may be diagnosed with premature ejaculation (PE), while men who experience difficulty achieving sexual climax may be diagnosed with delayed ejaculation (DE). The experience of many clinicians suggest that these problems are not rare and can be a source of considerable embarrassment and dissatisfaction for patients. The role of the clinician in managing PE and DE is to conduct appropriate investigation, to provide education, and to offer available treatments that are rational and based on sound scientific data. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. A research librarian conducted searches in Ovid MEDLINE (1946 to March 1, 2019), the Cochrane Central Register of Controlled Trials (through January 2019) and the Cochrane Database of Systematic Reviews (through March 1, 2019). An update search was conducted on September 5, 2019. Database searches resulted in 1,851 potentially relevant articles. After dual review of abstracts and titles, 223 systematic reviews and individual studies were selected for full-text dual review, and 8 systematic reviews and 59 individual studies were determined to meet inclusion criteria and were included in the review. RESULTS: Several psychological health, behavioral, and pharmacotherapy options exist for both PE and DE; however, none of these pharmacotherapy options have achieved approval from the United States Food and Drug Administration and their use in the treatment of PE and DE is considered off-label. CONCLUSION: Disturbances of the timing of ejaculation can pose a substantial impediment to sexual enjoyment for men and their partners. The Panel recommends shared decision-making as fundamental in the management of disorders of ejaculation; involvement of sexual partner(s) in decision making, when possible, may allow for optimization of outcomes.

Advances and Missteps in Diagnosing Premature Ejaculation: Analysis and Future Directions.

BACKGROUND: There are several problems with diagnostic criteria for premature ejaculation (PE) that lack objectivity, clarity and precision. They hamper accurate determination of PE prevalence estimates, investigations into the etiology of the dysfunction, impact on partners, development of validated Patient Reported Outcomes, regulatory authority oversight, and which men might benefit from specific treatment interventions. AIM: We sought to review, analyze and comment on the evolution of the definitions of PE and offer suggestions for future directions for PE definitions. Our goal is to propose strategies whereby the criterion sets are useful to researchers, clinicians and governmental oversight agencies alike and bring harmony and scientific rigor among the conflicting and confusing definitions. METHODS: There are several premature ejaculation definitions published in the peer reviewed medical literature. The PUBMED electronic database from 1970 to 2021 was searched for published definitions. Search terms included the medical subject headings of premature ejaculation, definition and diagnosis. In chronological order, Table 1 lists the various diagnosis and criteria sets for PE. We discuss the process by which constructs, which make up diagnostic criteria sets, are operationalized and validated. RESULTS: We review definitions of PE beginning with Masters and Johnson's focus on partner orgasmic attainment and move through the nebulous and subjective criterion sets found in the early Diagnostic and Statistical Manuals and International Classification of Disease series, to the more evidenced-based definitions found in International Society of Sexual Medicine, Diagnostic and Statistical Manuals-5 and the American Urological Association (AUA) definitions. Additionally, we discuss how constructs and criteria sets have been adopted to minimize errors of inclusion and exclusion in defining disease/dysfunction. STRENGTHS AND LIMITATIONS: This manuscript offers a careful chronological analysis of the published definitions of PE. This historical lens allows the reader to perceive the shifting science underlying the development of PE definitions. The manuscript is limited regarding our comments on acquired PE as evidenced-based research is incomplete. CONCLUSION: Over the past 50 years there has been considerable forward momentum in defining PE based on well conducted scientific studies. We support the American Urological Association's modification in Intravaginal ejaculatory latency time to 2-minutes for lifelong PE, concur with the 11th revision of the International Classification of Diseases recommendation for changing the terminology from premature ejaculation to early ejaculation. We also recommend ongoing validation of definitions, moving away from the current heterosexist definition of PE based on penile-vaginal sex and urge further population based research into acquired PE to develop stronger evidenced-based criterion sets for this subtype. Althof SE, McMahon CG, Rowland DL. Advances and Missteps in Diagnosing Premature Ejaculation: Analysis and Future Directions. J Sex Med 2022;19:64-73.

Pharmacokinetics, Clinical Efficacy, Safety Profile, and Patient-Reported Outcomes in Patients Receiving Subcutaneous Testosterone Pellets 900 mg for Treatment of Symptoms Associated With Androgen Deficiency.

BACKGROUND: Implantation of testosterone doses of at least 150 to 450 mg (ie, two to six pellets) is common clinical practice despite a lack of prospective data. AIM: To evaluate pharmacokinetics, clinical efficacy, safety, and patient-reported outcomes in men with androgen deficiency who received implantation of testosterone pellets (900 mg) in an open-label study. METHODS: Men with androgen deficiency (serum testosterone < 300 ng/dL [10.4 nmol/L]) were screened and received 12 testosterone pellets (900 mg). Serum hormone measurements (total and free testosterone, dihydrotestosterone, and estradiol) were obtained on days 1, 5, 8, 15, 29, 57, 85, and 113. All hormones were assayed using validated liquid chromatography and tandem mass spectrometry. OUTCOMES: Pharmacokinetics of selected hormones was determined. The patient-reported International Index of Erectile Function (IIEF), Center for Epidemiologic Studies Depression (CES-D), and Androgen Deficiency in the Aging Male (qADAM) questionnaires also were performed. Patients rated their satisfaction on a scale from 1 (very satisfied) to 5 (very dissatisfied). Adverse events were monitored throughout. RESULTS: Fifteen patients were included (mean age = 54.5 years, SD = 8.6 years). Mean baseline total testosterone concentration was 241.6 ng/dL (SD = 88.8 ng/dL; mean = 8.4 nmol/L, SD = 3.1 nmol/L). Mean testosterone serum concentrations fluctuated during the first 2 weeks (range = 300-1,000 ng/dL, 10.4-34.7 nmol/L) but remained higher than or equal to 300 ng/dL (10.4 nmol/L) through day 113. Concentrations of free testosterone, dihydrotestosterone, and estradiol mirrored that of total testosterone. Male functioning (IIEF score), depression (CES-D total score), and androgen-deficiency symptoms (qADAM total score) improved from baseline. Most patients were "very satisfied" (40.0%) or "quite satisfied" (26.7%) with treatment. Testosterone pellets were well tolerated. Pellet extrusion and polycythemia occurred in one patient each. CLINICAL IMPLICATIONS: Implantation of high doses (900 mg) of testosterone pellets are generally well tolerated and could provide clinical benefit for some patients. STRENGTHS AND LIMITATIONS: This study provides standardized data for the implantation of 12 testosterone pellets. However, the open-label uncontrolled design of this study and its small and ethnically non-diverse patient population limit the interpretation of these data, particularly the patient-reported outcomes. CONCLUSION: Implantation of 12 testosterone pellets (900 mg) was well tolerated and provided adequate and sustained serum testosterone concentrations. Additional randomized controlled trials are needed to confirm efficacy and safety findings. McMahon CG, Shusterman N, Cohen B. Pharmacokinetics, Clinical Efficacy, Safety Profile, and Patient-Reported Outcomes in Patients Receiving Subcutaneous Testosterone Pellets 900 mg for Treatment of Symptoms Associated With Androgen Deficiency. J Sex Med 2017;14:883-890.

The International Society for Sexual Medicine's Process of Care for the Assessment and Management of Testosterone Deficiency in Adult Men.

INTRODUCTION: In 2014, the International Society for Sexual Medicine (ISSM) convened a panel of experts to develop an evidence-based process of care for the diagnosis and management of testosterone deficiency (TD) in adult men. The panel considered the definition, epidemiology, etiology, physiologic effects, diagnosis, assessment and treatment of TD. It also considered the treatment of TD in special populations and commented on contemporary controversies about testosterone replacement therapy, cardiovascular risk and prostate cancer. AIM: The aim was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of diagnosis and management of TD for clinicians without expertise in endocrinology, such as physicians in family medicine and general urology practice. METHOD: A comprehensive literature review was performed, followed by a structured, 3-day panel meeting and 6-month panel consultation process using electronic communication. The final guideline was compiled from reports by individual panel members on areas reflecting their special expertise, and then agreed by all through an iterative process. RESULTS: This article contains the report of the ISSM TD Process of Care Committee. It offers a definition of TD and recommendations for assessment and treatment in different populations. Finally, best practice treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with TD. CONCLUSION: Development of a process of care is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to new insights into the pathophysiology of TD, as well as new, efficacious and safe treatments. We recommend that this process of care be reevaluated and updated by the ISSM in 4 years.

An update of the International Society of Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation (PE).

INTRODUCTION: In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychological, and combined treatments. It concluded by recognizing the continually evolving nature of clinical research and recommended a subsequent guideline review and revision every fourth year. Consistent with that recommendation, the ISSM organized a second multidisciplinary panel of experts in April 2013, which met for 2 days in Bangalore, India. This manuscript updates the previous guidelines and reports on the recommendations of the panel of experts. AIM: The aim of this study was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. METHOD: A comprehensive literature review was performed. RESULTS: This article contains the report of the second ISSM PE Guidelines Committee. It offers a new unified definition of PE and updates the previous treatment recommendations. Brief assessment procedures are delineated, and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION: Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. We again recommend that these guidelines be reevaluated and updated by the ISSM in 4 years.

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

INTRODUCTION: The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE. AIM: The aim of this article is to review and critique the current literature and develop a contemporary, evidence-based definition for acquired PE and/or a unified definition for both lifelong and acquired PE. METHODS: In April 2013, the ISSM convened a second Ad Hoc Committee for the Definition of Premature Ejaculation in Bangalore, India. The same evidence-based systematic approach to literature search, retrieval, and evaluation used by the original committee was adopted. RESULTS: The committee unanimously agreed that men with lifelong and acquired PE appear to share the dimensions of short ejaculatory latency, reduced or absent perceived ejaculatory control, and the presence of negative personal consequences. Men with acquired PE are older, have higher incidences of erectile dysfunction, comorbid disease, and cardiovascular risk factors, and have a longer intravaginal ejaculation latency time (IELT) as compared with men with lifelong PE. A self-estimated or stopwatch IELT of 3 minutes was identified as a valid IELT cut-off for diagnosing acquired PE. On this basis, the committee agreed on a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by (i) ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE); (ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and (iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy. CONCLUSION: The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definition for these conditions. This definition will enable researchers to design methodologically rigorous studies to improve our understanding of acquired PE.

Clinical efficacy, safety and tolerability of collagenase clostridium histolyticum for the treatment of peyronie disease in 2 large double-blind, randomized, placebo controlled phase 3 studies.

PURPOSE: IMPRESS (Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies) I and II examined the clinical efficacy and safety of collagenase Clostridium histolyticum intralesional injections in subjects with Peyronie disease. Co-primary outcomes in these identical phase 3 randomized, double-blind, placebo controlled studies included the percent change in the penile curvature abnormality and the change in the Peyronie disease questionnaire symptom bother score from baseline to 52 weeks. MATERIALS AND METHODS: IMPRESS I and II examined collagenase C. histolyticum intralesional injections in 417 and 415 subjects, respectively, through a maximum of 4 treatment cycles, each separated by 6 weeks. Men received up to 8 injections of 0.58 mg collagenase C. histolyticum, that is 2 injections per cycle separated by approximately 24 to 72 hours with the second injection of each followed 24 to 72 hours later by penile plaque modeling. Men were stratified by baseline penile curvature (30 to 60 vs 61 to 90 degrees) and randomized to collagenase C. histolyticum or placebo 2:1 in favor of the former. RESULTS: Post hoc meta-analysis of IMPRESS I and II data revealed that men treated with collagenase C. histolyticum showed a mean 34% improvement in penile curvature, representing a mean ± SD -17.0 ± 14.8 degree change per subject, compared with a mean 18.2% improvement in placebo treated men, representing a mean -9.3 ± 13.6 degree change per subject (p <0.0001). The mean change in Peyronie disease symptom bother score was significantly improved in treated men vs men on placebo (-2.8 ± 3.8 vs -1.8 ± 3.5, p = 0.0037). Three serious adverse events (corporeal rupture) were surgically repaired. CONCLUSIONS: IMPRESS I and II support the clinical efficacy and safety of collagenase C. histolyticum for the physical and psychological aspects of Peyronie disease.

Standard operating procedures in the disorders of orgasm and ejaculation.

INTRODUCTION: Ejaculatory/orgasmic disorders are common male sexual dysfunctions and include premature ejaculation (PE), inhibited ejaculation, anejaculation, retrograde ejaculation, and anorgasmia. AIM: 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. METHODS: 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. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, limited expert opinion, widespread internal committee discussion, public presentation, and debate. RESULTS: 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. CONCLUSIONS: Additional research is required to further the understanding of the disorders of ejaculation and orgasm.

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.

INTRODUCTION: Men with comorbid erectile dysfunction (ED) and premature ejaculation (PE) may be concomitantly prescribed a phosphodiesterase type 5 (PDE5) inhibitor and dapoxetine. AIM: 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. METHODS: 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. MAIN OUTCOME MEASURE: Stopwatch-measured average IELT, Clinical Global Impression of Change (CGIC) in PE, Premature Ejaculation Profile (PEP), and treatment-emergent adverse events (TEAEs). RESULTS: 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%). CONCLUSIONS: In men with PE and comorbid ED on a stable regimen of PDE5 inhibitor, dapoxetine provided meaningful treatment benefit and was generally well tolerated.

Baseline characteristics from an ongoing phase 3 study of collagenase clostridium histolyticum in patients with Peyronie's disease.

INTRODUCTION: Peyronie's disease (PD) is a localized penile collagen disorder of the tunica albuginea associated with significant physical deformity and psychological impairment. Current understanding of pretreatment characteristics in patients with chronic PD is limited by small samples, varied quality of assessments, and the lack of a PD-specific, validated measure of the psychosexual impact of PD. AIMS: Reporting baseline demographic and disease characteristics of the large multinational cohort of subjects with chronic PD who participated in the collagenase clostridium histolyticum (CCH, an investigational intralesional injection and minimally invasive intervention) phase 3 clinical study program. Findings from well-defined assessments, including the Peyronie's Disease Questionnaire (PDQ), the first validated PD-specific patient-reported measure of psychosexual impact, are reported. METHODS: Subjects included men≥18 years old with PD symptoms≥12 months and penile deformity between 30° and 90°. Analysis data included demographics, disease history, and psychosexual impact. MAIN OUTCOME MEASURES: Penile deformity, disease symptoms, the International Index of Erectile Function, and the PDQ were assessed. RESULTS: Eight hundred thirty-two subjects were enrolled from 64 sites across the United States and Australia. The mean age was 57.7 years; mean PD duration was 4.1 years. The majority of subjects had penile deformity≤60° (77.3%); mean penile deformity was 50.5°. Subjects reported having intercourse a mean of 10.2 times in the previous 3 months, 70.8% reported difficulty in performing vaginal intercourse, and 80.4% reported less frequent vaginal intercourse. Approximately 71.5% of subjects with severe (>60°) and 58.1% of subjects with mild/moderate (≤60°) penile deformity were "very bothered" or "extremely bothered" upon last look at their erect penis (P=0.0041), as measured by the PDQ. CONCLUSIONS: These data add to the body of knowledge regarding the clinical impact of chronic phase PD, including the PD-specific patient-reported psychosexual symptoms, using a large multinational chronic PD cohort in the CCH phase 3 clinical program.

The Unfinished Business of Defining Premature Ejaculation: The Need for Targeted Research.

INTRODUCTION: Fifteen years have passed since the International Society of Sexual Medicine first established the 3-pronged criteria for premature ejaculation (PE): a short ejaculation latency, lack of ejaculatory control, and bother/distress. Although the process of establishing valid criteria for any condition or disorder is an ongoing one, a dearth of targeted research on these criteria has hindered professional societies from updating and revising them. OBJECTIVES: To review and critique existing criteria used in the diagnosis of PE, to identify specific problems with them, and to recommend studies that will address shortcomings. METHODS: Each of the PE criteria was evaluated and compared against standard procedures for establishing validated measures. Following each analysis, targeted research to address the gaps has been recommended. RESULTS: Each PE criterion has shortcomings and each can be improved by using standard validation procedures, as noted by the targeted research outcomes. Professional societies can play an important role by encouraging broad participation in research that generates new and relevant data supporting, validating, or challenging the existing criteria. CONCLUSION: The concepts underlying the diagnostic criteria for PE have both broad consensus and functional utility. Nevertheless, much of the research investigating PE has uncritically adopted these criteria without concomitantly recognizing their limitations. These limitations prevent determining accurate prevalence rates, interpreting research findings with confidence, and establishing efficacious treatment outcomes. Rowland DL, Althof SE, McMahon CG. The Unfinished Business of Defining Premature Ejaculation: The Need for Targeted Research. Sex Med Rev 2022;10:323-340.

Oral agents for the treatment of premature ejaculation: review of efficacy and safety in the context of the recent International Society for Sexual Medicine criteria for lifelong premature ejaculation.

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.

Efficacy and safety of dapoxetine for the treatment of premature ejaculation: integrated analysis of results from five phase 3 trials.

INTRODUCTION: Dapoxetine has been evaluated for the on-demand treatment of premature ejaculation (PE) in five phase 3 studies in various populations worldwide and has recently been approved in several countries. AIM: To present integrated efficacy and safety data from phase 3 trials of dapoxetine. METHODS: Data were from five randomized, multicenter, double-blind, placebo-controlled studies conducted in over 25 countries. Men (N=6,081)≥18 years who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE; four studies required a baseline intravaginal ejaculatory latency time (IELT) of ≤2 minutes. Dapoxetine 30 and 60 mg on demand (prn; 1-3 hours before intercourse) were evaluated for either 12 or 24 weeks in four studies; one study evaluated dapoxetine 60 mg daily (qd; included in safety assessments only) or prn for 9 weeks. MAIN OUTCOME MEASURES: End points included stopwatch-measured IELT, Premature Ejaculation Profile (PEP) items, clinical global impression of change (CGIC) in PE, and adverse events (AEs). RESULTS: Average IELT (mean [standard deviation], geometric mean [standard error]) increased from baseline (across groups, 0.9 [0.49] minutes, 0.8 [1.01] minutes) to a significantly greater extent with dapoxetine 30 (3.1 [3.91] minutes, 2.0 [1.03] minutes) and 60 mg (3.6 [3.85] minutes, 2.3 [1.03] minutes) vs. placebo (1.9 [2.43] minutes, 1.3 [1.02] minutes; P<0.001 for all) at week 12 (geometric mean fold increase, 2.5, 3.0, and 1.6, respectively). All PEP items and CGIC improved significantly with both doses of dapoxetine vs. placebo (P<0.001 for all). The most common AEs included nausea, dizziness, and headache, and evaluation of validated instruments demonstrated no anxiety, akathisia, suicidality, or changes in mood with dapoxetine use and no discontinuation syndrome following abrupt withdrawal. CONCLUSIONS: In this diverse population, dapoxetine significantly improved all aspects of PE and was generally well tolerated.

Disorders of orgasm and ejaculation in men.

INTRODUCTION: Ejaculatory/orgasmic disorders are common male sexual dysfunctions, and include premature ejaculation (PE), inhibited ejaculation, anejaculation, retrograde ejaculation, and anorgasmia. AIM: To provide recommendations and guidelines concerning current state-of-the-art knowledge for management of ejaculation/orgasmic disorders in men. METHODS: An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 25 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge of disorders of orgasm and ejaculation represent the opinion of seven experts from seven countries developed in a process over a 2-year period. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. RESULTS: Premature ejaculation management is largely dependent upon etiology. Lifelong PE is best managed with PE pharmacotherapy (selective serotonin re-uptake inhibitor [SSRI] and/or topical anesthetics). The management of acquired PE is etiology specific and may include erectile dysfunction (ED) pharmacotherapy in men with comorbid ED. Behavioral therapy is indicated when psychogenic or relationship factors are present and is often best combined with PE pharmacotherapy in an integrated treatment program. Retrograde ejaculation is managed by education, patient reassurance, pharmacotherapy, or bladder neck reconstruction. Delayed ejaculation, anejaculation, and/or anorgasmia may have a biogenic and/or psychogenic atiology. Men with age-related penile hypoanesthesia should be educated, reassured, and instructed in revised sexual techniques which maximize arousal. CONCLUSIONS: Additional research is required to further the understanding of the disorders of ejaculation and orgasm.

Baseline characteristics and treatment outcomes for men with acquired or lifelong premature ejaculation with mild or no erectile dysfunction: integrated analyses of two phase 3 dapoxetine trials.

INTRODUCTION: Premature ejaculation (PE) is classified as an acquired or lifelong condition but data on baseline characteristics and response to treatment of men with acquired or lifelong PE and mild erectile dysfunction (ED) or normal erectile function (EF) is limited. AIM: To present integrated analyses of baseline characteristics and treatment outcomes from phase 3 dapoxetine trials in men with acquired or lifelong PE and mild or no ED. METHODS: Data were analyzed from two randomized, double-blind, placebo-controlled, phase 3 clinical trials (International and Asia-Pacific) that evaluated efficacy and safety of dapoxetine (30 mg or 60 mg as needed [PRN]) in patients with PE. Men were ≥18 years, in a stable monogamous relationship for ≥6 months, met DSM-IV-TR criteria for PE for ≥6 months, had an International Index of Erectile Function EF domain score ≥21, and had an intravaginal ejaculatory latency time (IELT) ≤2 minutes in ≥75% of intercourse episodes. MAIN OUTCOME MEASURES: Demographics, sexual history, and PE symptomatology at baseline, and mean IELT and patient-reported outcomes (PROs) at study end (week 12), were analyzed for men with acquired or lifelong PE and mild or no ED (EF score 21-25 vs. ≥26). RESULTS: Baseline characteristics except duration of PE were similar in men with acquired and lifelong PE, with no other differentiating features by ED status. Dapoxetine treatment improved significantly mean IELT (arithmetic and geometric) and PRO responses (perceived control over ejaculation, satisfaction with sexual intercourse, ejaculation-related personal distress, and interpersonal difficulty) for acquired and lifelong subtypes, but presence of mild ED diminished PRO responsiveness in both subtypes, particularly those with lifelong PE. CONCLUSIONS: Baseline characteristics and treatment outcomes were generally similar in men with acquired and lifelong PE. The presence of mild ED appears to be associated with a more modest treatment response, irrespective of lifelong or acquired PE subtype.

International Society for Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation.

INTRODUCTION: Over the past 20 years our knowledge of premature ejaculation (PE) has significantly advanced. Specifically, we have witnessed substantial progress in understanding the physiology of ejaculation, clarifying the real prevalence of PE in population-based studies, reconceptualizing the definition and diagnostic criterion of the disorder, assessing the psychosocial impact on patients and partners, designing validated diagnostic and outcome measures, proposing new pharmacologic strategies and examining the efficacy, safety and satisfaction of these new and established therapies. Given the abundance of high level research it seemed like an opportune time for the International Society for Sexual Medicine (ISSM) to promulgate an evidenced-based, comprehensive and practical set of clinical guidelines for the diagnosis and treatment of PE. AIM: Develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. Method. Review of the literature. RESULTS: This article contains the report of the ISSM PE Guidelines Committee. It affirms the ISSM definition of PE and suggests that the prevalence is considerably lower than previously thought. Evidence-based data regarding biological and psychological etiology of PE are presented, as is population-based statistics on normal ejaculatory latency. Brief assessment procedures are delineated and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. CONCLUSION: Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. Therefore, it is strongly recommended that these guidelines be re-evaluated and updated by the ISSM every 4 years.

Summary of the recommendations on sexual dysfunctions in men.

INTRODUCTION: Sexual health is an integral part of overall health. Sexual dysfunction can have a major impact on quality of life and psychosocial and emotional well-being. AIM: To provide evidence-based, expert-opinion consensus guidelines for clinical management of sexual dysfunction in men. METHODS: An international consultation collaborating with major urologic and sexual medicine societies convened in Paris, July 2009. More than 190 multidisciplinary experts from 33 countries were assembled into 25 consultation committees. Committee members established scope and objectives for each chapter. Following an exhaustive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measures. New algorithms and guidelines for assessment and treatment of sexual dysfunctions were developed based on work of previous consultations and evidence from scientific literature published from 2003 to 2009. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of medical literature, and cultural and ethical considerations. RESULTS: Algorithms, recommendations, and guidelines for sexual dysfunction in men are presented. These guidelines were developed in an evidence-based, patient-centered, multidisciplinary manner. It was felt that all sexual dysfunctions should be evaluated and managed following a uniform strategy, thus the International Consultation of Sexual Medicine (ICSM-5) developed a stepwise diagnostic and treatment algorithm for sexual dysfunction. The main goal of ICSM-5 is to unmask the underlying etiology and/or indicate appropriate treatment options according to men's and women's individual needs (patient-centered medicine) using the best available data from population-based research (evidence-based medicine). Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronie's disease; and priapism. CONCLUSIONS: Sexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective.

Screening for erectile dysfunction in men with lifelong premature ejaculation--Is the Sexual Health Inventory for Men (SHIM) reliable?

INTRODUCTION: Some men with premature ejaculation (PE) and normal erectile function record contradictory response/s to The Sexual Health Inventory for Men (SHIM) and may be incorrectly categorized as suffering from erectile dysfunction (ED). AIMS: The aim of this study was to evaluate the frequency of false positive SHIM diagnosis of ED in men with lifelong PE. MAIN OUTCOME MEASURES: SHIM, stopwatch intravaginal ejaculation latency time (IELT). METHODS: A prospective observational study of men with normal erectile function and lifelong PE, diagnosed using the ISSM definition of lifelong PE, was conducted. The SHIM was self-administered at Visit 1. Mean per subject stopwatch IELT was determined from four subsequent intercourse attempts. RESULTS: Seventy-eight subjects with a mean age of 33.2 +/- 8.3 years and a geometric mean IELT of 15.9 +/- 2.3 seconds were enrolled. The mean SHIM score for all subjects was 20.4 +/- 6.0. Fifty-two subjects (66.7%) have SHIM scores of >21 (mean 24.3 +/- 1.1), consistent with normal erectile function, and a geometric mean IELT of 18.3 +/- 2.2 seconds. Twenty-six subjects (33.3%) had SHIM scores <22 (mean 12.7 +/- 3.7), consistent with a false positive diagnosis of ED, and a geometric mean IELT of 10.5 +/- 2.3 seconds. The incidence of false positive SHIM diagnosis of ED (SHIM < 22) was inversely related to the IELT. Although the geometric mean IELT for subjects with SHIM scores <22 was significantly less than that of all subjects and subjects with SHIM scores >21, there were no significant differences between the geometric mean IELT or the IELT distribution of all subjects vs. the normal erectile function IELT (SHIM > 21) cohort. CONCLUSION: This study demonstrates a 33.3% false positive SHIM diagnosis of ED in men with PE. This is likely to limit subject recruitment in clinical trials by exclusion of subjects with low-range IELTs but is unlikely to result in significantly different baseline IELTs or IELT distributions.

Is sex just fun? How sexual activity improves health.

INTRODUCTION: With nonscientific, religious, or magic arguments, sexual activity has been regarded in the past as dangerous to health. This opinion is now rejected, and intercourse is generally considered healthy. However, while some aspects of the equation "more sex equals more health" have been demonstrated, others still need robust data for confirmation. METHODS: Four scientists (an endocrinologist, a psychologist, a gynecologist, and a urologist) with expertise in the area of sexual medicine were asked to contribute with their opinions. MAIN OUTCOME MEASURE: Expert opinion supported by currently available literature. RESULTS: Expert 1, who is Controversy's section editor, demonstrates that sexual activity stimulates testosterone production. He infers that this physiological stimulus to androgenic production is one of the reasons why sexual activity improves general health. He is partially supported by the psychological findings in the couple having sex dissected by expert 2 and by the experimental evidences discussed by expert 3, who found that general benefits of sexual activity are not just for men. Expert 4 critically discusses contrasting findings so far published on the relationship between sexual activity and prostate cancer. He, in general agreement with the remainder of the faculty, stresses the need for more research on this entire topic. CONCLUSION: Readers of The Journal of Sexual Medicine will judge if safe, satisfactory, and frequent sexual activity can be prescribed as a medicine in order to improve both general and sexual health of individuals and of the couples.