Symptoms and associated impact in pre- and postmenopausal women with sexual arousal disorder: a concept elicitation study.

BACKGROUND: Approximately 26% of adult women in the United States suffer from female sexual arousal disorder (FSAD), yet little has been done to compare the experience of FSAD in pre- and postmenopausal women, which is critical to enhance the current understanding of FSAD and inform the development and assessment of treatment options for these patient populations. AIM: To explore the experience of condition-associated symptoms and the relative importance of FSAD symptoms, including their severity, bother, and impact, on participants' health-related quality of life (HRQoL) in pre- and postmenopausal women with FSAD. METHODS: In-depth, qualitative, semistructured concept elicitation interviews were conducted with premenopausal (n = 23) and postmenopausal (n = 13) women who were clinically diagnosed with FSAD by a trained sexual medicine clinician. All interviews were audio recorded and transcribed verbatim by a professional transcription company. Thematic analysis was performed with the assistance of NVivo qualitative analysis software. OUTCOMES: Outcomes included qualitative interview data about FSAD symptoms and HRQoL, as well as a comparison between pre- and postmenopausal populations. RESULTS: The most frequently reported symptom in both cohorts was "inability or difficulty with orgasm" (premenopausal, n = 21; postmenopausal, n = 13). The symptom that premenopausal women most desired to have treated was lubrication, and for postmenopausal women, it was a lack of lubrication or wetness and loss of feeling/sensation. In total, 21 of 23 premenopausal women and all 13 postmenopausal women reported a lack of feeling or sensation in the genitals. The most frequently reported HRQoL impact in both groups was decreased confidence. CLINICAL IMPLICATIONS: Results from this study suggest that the manifestation and experience of FSAD are similar in pre- and postmenopausal women and that the unmet need for an FSAD treatment in the postmenopausal population is just as great as that of the premenopausal population. STRENGTHS AND LIMITATIONS: This study involved in-depth qualitative interviews with a relatively small group of women (N = 36) recruited from only 5 study sites across the United States. CONCLUSION: The analysis of qualitative data from the concept elicitation interviews revealed a substantial physical and emotional burden of FSAD, underscoring the need for Food and Drug Administration-approved treatment options for pre- and postmenopausal women with FSAD.

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.

Erectile Dysfunction is a Modifiable Risk Factor for Major Depressive Disorder: Analysis of a Federated Research Network.

BACKGROUND: Erectile dysfunction is one of many conditions associated with depression, but few studies exist to establish the risk of major depressive disorder (MDD) in the large population of men with erectile dysfunction, and it is unclear whether erectile dysfunction (ED) treatment is associated with decreased rates of MDD. AIM: We determined the risk of major depressive disorder in men with erectile dysfunction and evaluated whether treatment of ED with phosphodiesterase-5 inhibitor or penile prosthesis is associated with a lower risk of developing major depressive disorder. METHODS: We reviewed a large, retrospective, cohort that utilized electronic health record data collected by the TriNetX Research Network, a global federated database that provides healthcare data for analysis. We performed multiple comparisons: men with ED against men without ED; men with ED treated with phosphodiesterase-5 inhibitors against untreated ED patients, and of men with ED who received penile prosthesis against those who did not. We assessed major depressive disorder (ICD-10-CM F32-F33) as a primary outcome and used propensity score matching to control for ethnicity, race, type 2 diabetes mellitus (E11), essential hypertension (I10), acute myocardial infarction (I21), chronic ischemic heart disease (I25), cerebral infarction (I63), overweight and obesity (E66), personal history of nicotine (Z87.891), hypogonadism (E29.1), and alcohol related disorders (F10). OUTCOMES: We assessed new diagnosis of major depressive disorder (F32-F33) within a 3-year time window following index event of ED diagnosis, visit to healthcare organization, or ED treatment with phosphodiesterase-5 inhibitor or penile prosthesis as the primary outcome. RESULTS: ED was associated with major depressive disorder both before and after (OR 2.00, 95% CI 1.94-2.06) controlling for confounding variables through propensity score matching. Men who received ED therapies had lower rates of depression compared to those who did not, whether they were treated with phosphodiesterase-5 inhibitor (0.80, 0.77-0.83) or penile prosthesis (0.73, 0.60-0.89). STRENGTHS AND LIMITATIONS: Strengths include a large sample size and robust statistical techniques. Limitations include lack of detailed information regarding clinical severity and socioeconomic factors. CLINICAL IMPLICATIONS: Our findings indicate that clinicians should consider evaluating depressive symptoms among men with erectile dysfunction and counsel them regarding the risk of developing major depressive disorder. CONCLUSIONS: Erectile dysfunction is associated with major depressive disorder, but treatment is associated with decreased rates of MDD. S Nackeeran, A Havanur, J Ory, et al. Erectile Dysfunction is a Modifiable Risk Factor for Major Depressive Disorder: Analysis of a Federated Research Network. J Sex Med 2021;18:2005-2011.

Development and Validation of the Satisfaction Survey for Inflatable Penile Implant (SSIPI).

BACKGROUND: No validated English language patient-reported outcome (PRO) currently exists that assesses satisfaction with inflatable penile prosthesis (IPP). Satisfaction data have been largely based primarily on surgeon assessment of patients or using questionnaires that have not been designed for this purpose. AIM: To develop an English-language validated PRO that assesses patient satisfaction after IPP surgery. METHODS: Initially, a literature review and discussions with experts defined domains important to IPP satisfaction (pain, appearance, function, overall satisfaction). The initial 35-item Satisfaction Survey for Inflatable Penile Implant (SSIPI) was developed. Cognitive interviews were then performed with IPP patients (n = 12) to gain feedback on the SSIPI domains and items. These data were used to modify SSIPI with the addition of 2 questions for a final item number of 37. Patients from 4 centers, who were between 6 months and 5 years after IPP, were administered the questionnaire through RedCap. Reliability statistics and content analysis were used to winnow questions to yield the final 16-item version of the SSIPI. Internal consistency was assessed via Cronbach's alpha and item-total correlation. Test-retest reliability was assessed via intraclass correlation coefficients using baseline and 2-week data. For convergent validity, the Erectile Dysfunction Inventory of Treatment Satisfaction and the Self-Esteem and Relationship (SEAR) questionnaire were used. For discriminant validity, the International Prostate Symptom Score (IPSS) was used. Confirmatory factor analysis was used to assess the factor structure of the SSIPI. OUTCOMES: Internal consistency, test-retest reliability, convergent and discriminant validity, and confirmatory factor analysis were assessed. RESULTS: 118 men were surveyed. Mean age was 66.8 ± 9.5 years. The 16-item SSIPI showed high internal consistency with an overall Cronbach's Alpha of 0.97 (domains 0.85-0.89). Item-total correlations for individual items to subscales ranged from 0.60 to 0.91. The overall test-retest reliability was 0.94 (domains 0.87-0.93). Erectile Dysfunction Inventory of Treatment Satisfaction and Self-Esteem and Relationship had correlations of 0.84 overall (domains 0.57-0.79) and 0.47 overall (domains 0.34-0.44), respectively. International Prostate Symptom Score (discriminant validity) had correlations of -0.29 overall (domains -0.17 to -0.31). CLINICAL IMPLICATIONS: SSIPI is the first English-language validated IPP satisfaction PRO. This will enable clinicians to collect satisfaction data in a standardized way. STRENGTHS AND LIMITATIONS: As strengths we have used a rigorous psychometric process and have no industry sponsorship. Limitations include small numbers of specific subpopulations. CONCLUSION: The SSIPI has demonstrated robust psychometric properties. Salter CA, Bach PV, Jenkins L, et al. Development and Validation of the Satisfaction Survey for Inflatable Penile Implant (SSIPI). J Sex Med 2021;18:1641-1651.

Objective and Subjective Measures of Premature Ejaculation: How Closely Do They Correspond and How Well Are the Subjective Measures Recalled?

BACKGROUND: Clinical trials evaluating new treatments for premature ejaculation (PE) should ideally include both objective end points and patient reported outcomes (PROs), but there is no consensus currently over the optimal measures or combination of outcomes. In addition, many PROs use a 1-month recall period, despite concerns about potential recall bias. AIMS: Data from a clinical trial of men with lifelong PE were used to examine the consistency of 2 core items of the Premature Ejaculation Profile (PEP), a widely used PRO for assessing subjective aspects of PE. The specific aim was to assess the level of agreement between the original 1-month recall version compared with a new event-based version of the scale in men meeting current definitions of lifelong PE. A further aim was to investigate the convergent validity between an objective end point of intravaginal ejaculatory latency time (IELT), subjective PEP responses, and a patient's Clinical Global Impression of Change (CGIC) measure. METHODS: For assessment of consistency of PEP responses (short-term [ie, sexual event driven] vs 1-month recall), descriptive statistics, correlation coefficients (Pearson and Spearman), and Bland-Altman plots are presented for each time interval. For assessment of convergent validity, descriptive statistics and correlation coefficients (Pearson and Spearman) are presented for each assessment with geometric mean IELT values. Results are also depicted graphically. Geometric mean IELT over the last 4 weeks of treatment and change from baseline (absolute and fold change) were estimated via a general linear model for each category of change in PEP and CGIC, adjusting for baseline IELT. OUTCOMES: PEP items administered via 1-month recall and short-term event-driven responses gave virtually identical results. There was a strong correlation (very good convergent validity) between IELT and responses to PEP and the CGIC. CLINICAL TRANSLATION: Men with lifelong PE can accurately recall their level of sexual functioning over the previous month. The PEP and CGIC are appropriate instruments to measure the subjective response of men with PE to new treatments. STRENGTHS AND LIMITATIONS: Our analyses address gaps in previously published research on PE assessment methodology. Men with acquired PE, men without partners, and men in homosexual relationships were not studied. CONCLUSIONS: In a clinical trial setting, PEP and CGIC are appropriate end points and are likely the optimal combination of PROs for use with IELT to enable a global assessment of patient response to new PE treatments. Althof S, Rosen R, Harty B, et al. Objective and Subjective Measures of Premature Ejaculation: How Closely Do They Correspond and How Well Are the Subjective Measures Recalled? J Sex Med 2020;17:634-644.

The Oxytocin Antagonist Cligosiban Fails to Prolong Intravaginal Ejaculatory Latency in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Phase IIb trial (PEDRIX).

INTRODUCTION: Cligosiban is an orally administered, centrally penetrant oxytocin receptor antagonist being developed to treat premature ejaculation (PE). AIM: To determine the efficacy of 3 dose levels of cligosiban caplets to prolong intravaginal ejaculation latency time (IELT) and improve patient-reported outcomes in men with lifelong PE. METHODS: Patients recorded details of at least 4 sexual intercourse events during a 4-week run-in period, after which they underwent baseline assessments. Patients were eligible for the study if their stopwatch-assessed IELT was ≤1 minute in ≥75% of intercourse attempts and if they met other diagnostic criteria for lifelong PE. Eligible patients (target 220 evaluable) were randomized to double-blind cligosiban 400, 800, or 1200 mg or matching placebo caplets (to be taken 1 to 6 hours prior to sexual activity). Assessments were conducted at 2, 4, and 8 weeks. MAIN OUTCOME MEASURE: Efficacy measures were comprised of IELT, self-rating of ejaculation control and ejaculation-related distress (recorded in an electronic diary after each intercourse attempt), premature ejaculation profile, Patient's Global Impression of Severity, and the Clinical Global Impression of Change. RESULTS: There were no clinically or statistically significant differences between cligosiban (at any dose level) and placebo for the primary endpoint (change in geometric IELT) or any of the secondary endpoints. Cligosiban was well tolerated with a side-effect profile similar to placebo. CLINICAL IMPLICATIONS: This Phase IIb study failed to demonstrate the potential for cligosiban, an oxytocin antagonist, to successfully treat symptoms of severe lifelong PE at doses up to 1200 mg. STRENGTHS AND LIMITATIONS: This was a Phase IIb, randomized, double-blind, placebo-controlled study that was adequately powered but failed to detect a clinically meaningful or statistical difference in change in IELT between cligosiban at 3 dose levels and placebo. This is in contrast to a similarly designed proof-of-concept study where cligosiban was flexibly dosed at doses up to 800 mg and did demonstrate clinically meaningful and statistically significant changes in efficacy parameters. The reasons for this disparity are not known. CONCLUSIONS: Cligosiban was well tolerated but failed to demonstrate efficacy for the treatment of men with lifelong PE at doses up to 1200 mg. Althof S, Osterloh IH, Muirhead GJ, et al. The Oxytocin Antagonist Cligosiban Fails to Prolong Intravaginal Ejaculatory Latency in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Phase IIb trial (PEDRIX). J Sex Med 2019; 16:1188-1198.

The Oxytocin Antagonist Cligosiban Prolongs Intravaginal Ejaculatory Latency and Improves Patient-Reported Outcomes in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Trial (PEPIX).

INTRODUCTION: Cligosiban is an orally administered oxytocin receptor antagonist being developed to treat premature ejaculation (PE). AIM: To determine the safety and efficacy of cligosiban capsules (dose range 400-800 mg) to improve intravaginal ejaculation latency time (IELT) and patient-reported outcomes in men with severe lifelong PE. METHODS: Patients recorded details of at least 4 sexual intercourse events during a 4-week run-in period, after which they underwent baseline assessments. Patients were eligible for the study if they rated their control of ejaculation as poor/very poor and their stopwatch-assessed IELT was ≤1 minute in ≥75% of intercourse attempts. Eligible patients were randomized to an 8-week treatment period with double-blind cligosiban or placebo (to be taken 1 to 6 hours prior to sexual activity). The starting dose was 400 mg (not more than 1 dose per day) which could be increased to 800 mg after 2 and/or 4 weeks of treatment. Assessments were conducted at 2, 4, and 8 weeks. MAIN OUTCOME MEASURE: Efficacy measures were comprised of IELT, self-rating of ejaculation control and ejaculation-related distress (recorded in an electronic diary after each intercourse attempt), premature ejaculation profile, and the Clinical Global Impression of Change. RESULTS: The mean ratio of fold change from baseline in IELT to the last 4 weeks of treatment (cligosiban/placebo) was 1.9 compared to a baseline of 1.0 (P = .0079). The mean increase in IELT from baseline to the last 4 weeks of treatment was 61.0 seconds for cligosiban, which was significantly different from (and 3.6-fold greater than) the mean increase of 16.4 seconds for placebo (P = .0086). Statistically significant improvements in ejaculation control and ejaculation-related personal distress scores were also observed for cligosiban compared to little or no change with placebo. Cligosiban was generally well tolerated, with no serious or severe adverse events or other safety parameters. CLINICAL IMPLICATIONS: This proof-of-concept study demonstrated the potential for cligosiban, an oxytocin antagonist, to successfully treat symptoms of severe lifelong PE. STRENGTHS AND LIMITATIONS: This was a Phase II, randomized, double-blind, placebo-controlled study that was adequately powered to detect a clinically meaningful difference in change in IELT between cligosiban and placebo. Larger studies will be needed to confirm these findings, determine the optimal dose of cligosiban and assess efficacy in men with acquired PE. CONCLUSIONS: Cligosiban was well tolerated, and resulted in significant benefits in both objective and subjective measures of ejaculatory control in men with lifelong PE and therefore offers significant potential as an on-demand, orally administered agent for the treatment of PE. McMahon C, Althof S, Rosen R, et al. The Oxytocin Antagonist Cligosiban Prolongs Intravaginal Ejaculatory Latency and Improves Patient-Reported Outcomes in Men with Lifelong Premature Ejaculation: Results of a Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Trial (PEPIX). J Sex Med 2019; 16:1178-1187.

Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide.

BACKGROUND: Responder analyses are used to determine whether changes that occur during a clinical trial are clinically meaningful; for subjective endpoints such as those based on patient-reported outcomes (PROs), responder analyses are particularly useful. AIM: To identify the minimal clinically important difference (MCID) for selected scores on questionnaires assessing female sexual functioning and to use these differences to analyze the response in a large, controlled, phase 2b, dose-finding study of bremelanotide in premenopausal women with hypoactive sexual desire disorder (HSDD) and mixed HSDD/female sexual arousal disorder (FSAD). METHODS: The responder analyses were performed for the change from baseline to end of study for a total of 7 endpoints. Each PRO endpoint was assessed using at least 1 of 4 types of responder analyses: a planned analysis anchored to MCIDs based on expert estimates (historical anchors); post hoc analyses based on self-reported global benefit; receiver operating characteristic (ROC) curves; and cumulative distribution function. The prespecified analysis groups were all female sexual dysfunction (FSD)-based diagnoses (all study participants), those with HSDD alone, and a combined group of those with FSAD alone plus those with mixed HSDD/FSAD. Post hoc analyses were also performed for subjects with mixed HSDD/FSAD with a primary diagnosis of HSDD. OUTCOMES: MCIDs based on the ROC curves for changes in Female Sexual Function Index-desire domain, Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) total score, FSDS-DAO item 13 and 14 scores, and number of satisfying sexual events. RESULTS: Outcomes matched those based on input from clinical experts. For all 7 endpoints, responder rates at the 1.75 mg dose in the overall modified intention-to-treat population achieved statistical significance compared with placebo (P ≤ .03). CLINICAL IMPLICATIONS: These responder definitions were subsequently used in the bremelanotide phase 3 registration studies (RECONNECT) that evaluated the safety and efficacy of the bremelanotide 1.75 mg subcutaneous dose in premenopausal women with HSDD. STRENGTHS & LIMITATIONS: MCIDs for this study were based on changes from a single-blind phase to account for changes due to the placebo effect. These analyses were restricted to a study population composed only of premenopausal women with a clinical diagnosis of HSDD and/or FSAD and were based on data from the same clinical trial. CONCLUSION: Bremelanotide was safe and well tolerated and demonstrated significant improvement in efficacy vs placebo in the phase 2b trial. The multiple responder analyses offer a valuable approach for determining clinically important effects of bremelanotide for HSDD and FSAD. Althof S, Derogatis LR, Greenberg S, et al. Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide. J Sex Med 2019;16:1226-1235.

Toward a More Evidence-Based Nosology and Nomenclature for Female Sexual Dysfunctions-Part III.

INTRODUCTION: In 2016 the International Society for the Study of Women's Sexual Health (ISSWSH) published an expert consensus report on new nomenclature that addressed the need for comprehensive, evidence-based criteria for new diagnoses in desire, arousal, and orgasm, with the definition on arousal focusing exclusively on female genital arousal disorder (FGAD). AIM: A new expert panel solely focused on mechanisms of arousal disorders convened to revise the nomenclature to include female cognitive arousal disorder (FCAD) and FGAD. METHODS: The ISSWSH co-chairs identified experts on arousal disorders in women. The 10 participants included clinicians, researchers, and educators, representing a diverse, multidisciplinary group. Pre-meeting preparation included evidence-based literature review as the basis of presentations panelists made at the meeting on the current knowledge in cognitive arousal. Consensus was reached using a modified Delphi method. Writing assignments were made as a basis of manuscript development. MAIN OUTCOME MEASURES: The new definition of FCAD is characterized by distressing difficulty or inability to attain or maintain adequate mental excitement associated with sexual activity, as manifested by problems with feeling engaged and mentally turned on or sexually aroused for a minimum of 6 months. RESULTS: Female sexual arousal disorder encompasses both FGAD (revised definition) and FCAD (new definition). Recommendations regarding diagnosis include a clinical interview to assess for FCAD using targeted questions. Patient-reported outcomes that contain questions to assess FCAD are described, including limitations for differentiating between cognitive arousal, genital arousal, and sexual desire. Laboratory measures of cognitive and genital arousal are discussed, including the relationships between genital and cognitive arousal patterns. Biopsychosocial risk factors for FCAD and FGAD, as well as exclusionary conditions, are presented. CLINICAL IMPLICATIONS: The revision of the ISSWSH nomenclature regarding the criteria for the 2 arousal categories, FCAD and FGAD, and the recommended diagnostic strategies offers a framework for management of women with arousal disorders. STRENGTHS & LIMITATIONS: This nomenclature allows for basic science and clinical research in subtypes of arousal in order to develop better diagnostic and treatment options for use by clinicians, scientists, and regulatory agencies. There are limited validated measures of cognitive arousal, including the Female Sexual Function Index, the most commonly used measure, which does not effectively distinguish between cognitive excitement, genital sensations, and event-related desire. CONCLUSION: Future directions include the refinement of FCAD and FGAD and development and validation of patient-reported outcomes that distinguish between the cognitive processes and genital responses to enhance clinical care and research in this area. Parish SJ, Meston CM, Althof SE, et al. Toward a More Evidence-Based Nosology and Nomenclature for Female Sexual Dysfunctions-Part III. J Sex Med 2019;16:452-462.

Clinically important difference on the Erectile Dysfunction Inventory of Treatment Satisfaction questionnaire in patients with erectile dysfunction.

AIM: To determine what constitutes a clinically important difference (CID) on the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), an 11-item validated questionnaire assessing treatment satisfaction used in clinical trials for patients with erectile dysfunction (ED). METHODS: Erectile Dysfunction Inventory of Treatment Satisfaction data were evaluated from a double-blind, fixed-dose trial of 279 men aged 18-65 years with ED who were treated with sildenafil 50 or 100 mg or placebo. The primary anchor measure was the erectile function (EF) domain of the International Index of Erectile Function (IIEF), which has a 4-point minimal CID. The CID on the EDITS index score was determined using a regression analysis comparing EDITS and IIEF EF scores at the end of the 8-week treatment. A similar analysis was performed for EDITS and the Erection Hardness Score (EHS) instrument, a single-item questionnaire measuring hardness, which was used as a secondary anchor measure. RESULTS: Erectile Dysfunction Inventory of Treatment Satisfaction and IIEF EF domain scores were highly correlated (Pearson correlation coefficient = 0.75). EDITS total scores across treatments at week 8 averaged (mean ± standard deviation [SD]) 67.5 ± 21.6 (range, 0-100; higher scores indicate greater treatment satisfaction); IIEF EF domain scores averaged 22.2 ± 6.9 (range, 1-30; higher scores indicate higher erectile functioning). The calculated CID for EDITS scores was 9.5 (95% CI, 8.5-10.4; 0.44 SD units), corresponding to a medium effect size. EDITS and EHS instrument scores also correlated highly (Pearson correlation coefficient = 0.64). Placebo-adjusted EDITS mean scores were more than twice the CID, at 23 (95% CI, 17-28) and 28 (95% CI, 23-33) for the 50- and 100-mg doses, respectively. CONCLUSION: Approximately 10 points on the EDITS index score is considered a CID. Serving as a benchmark, this finding aids interpretation of the clinical relevance of a difference in mean EDITS index scores between treatments for patients with ED.

Delayed Ejaculation and Associated Complaints: Relationship to Ejaculation Times and Serum Testosterone Levels.

BACKGROUND: Although delayed ejaculation (DE) is typically characterized as a persistently longer than anticipated or desired time to ejaculation (or orgasm) during sexual activity, a timing-based definition of DE and its association with serum testosterone has not been established in a large cohort. AIM: To examine in an observational study estimated intravaginal ejaculatory latency time (IELT) and masturbatory ejaculation latency time (MELT) in men self-reporting DE, assess the association of IELT and MELT with serum testosterone levels, and determine whether correlation with demographic and sexual parameters exist. METHODS: Men who resided in the United States, Canada, and Mexico were enrolled from 2011 to 2013. Self-estimated IELT and MELT were captured using an Ejaculatory Function Screening Questionnaire in a sample of 988 men screened for possible inclusion in a randomized clinical trial assessing testosterone replacement therapy for ejaculatory dysfunction (EjD) and who self-reported the presence or absence of DE and symptoms of hypogonadism. Additional comorbid EjDs (ie, anejaculation, perceived decrease in ejaculate volume, and decreased force of ejaculation) were recorded. Men with premature ejaculation were excluded from this analysis. IELT and MELT were compared between men self-reporting DE and men without DE. The associations of IELT and MELT with serum testosterone were measured. OUTCOMES: IELT, MELT, and total testosterone levels. RESULTS: Sixty-two percent of screened men self-reported DE with or without comorbid EjDs; 38% did not report DE but did report at least one of the other EjDs. Estimated median IELTs were 20.0 minutes for DE vs 15 minutes for no DE (P < .001). Estimated median MELTs were 15.0 minutes for DE vs 8.0 minutes for no DE (P < .001). Ejaculation time was not associated with serum testosterone levels. Younger men and those with less severe erectile dysfunction had longer IELTs and MELTs. CLINICAL IMPLICATIONS: Estimated ejaculation times during vaginal intercourse and/or masturbation were not associated with serum testosterone levels in this study; thus, routine androgen evaluation is not indicated in these men. STRENGTHS AND LIMITATIONS: This large systematic analysis attempted to objectively assess the ejaculation latency in men with self-reported DE. Limitations were that ejaculation time estimates were self-reported and were queried only once; the questionnaire did not distinguish between failure to achieve orgasm and ejaculation; and assessment of DE was limited to heterosexual vaginal intercourse and masturbation. CONCLUSION: IELT and MELT were longer in men with DE, and there was no association of ejaculation times with serum testosterone levels in this study population. Morgentaler A, Polzer P, Althof S, et al. Delayed Ejaculation and Associated Complaints: Relationship to Ejaculation Times and Serum Testosterone Levels. J Sex Med 2017;14:1116-1124.

Opinion Paper: On the Diagnosis/Classification of Sexual Arousal Concerns in Women.

BACKGROUND: In the professional literature and among our professional societies, female sexual dysfunction nomenclature and diagnostic criterion sets have been the source of considerable controversy. Recently, a consensus group, supported by the International Society for Women's Sexual Health, published its recommendations for nosology and nomenclature, which included only one type of arousal dysfunction, female genital arousal disorder, in its classification system. Subjective arousal was considered an aspect of sexual desire and not part of the arousal phase. AIM: To advocate for the importance of including subjective arousal disorder in the diagnostic nomenclature in addition to the genital arousal subtype. METHODS: We reviewed how the construct of subjective arousal was included in or eliminated from the iterations of various diagnostic and statistical manuals. The Female Sexual Function Index (FSFI) was used to examine the relations among subjective arousal, genital arousal, and desire in women with and without sexual arousal concerns. MAIN OUTCOME MEASURES: Sexual arousal through a self-report Film Scale, physiologic sexual arousal through vaginal photoplethysmography in response to an erotic film, and the FSFI. RESULTS: The clinical literature and experience support differentiating subjective arousal from desire and genital arousal. Correlations between the FSFI domains representing desire and subjective arousal, although sufficient to suggest relatedness, share approximately 58% of the variance between constructs-a lower shared variance than FSFI domains representing subjective arousal and orgasm. Similarly, when looking at FSFI individual items best representative of sexual desire and subjective arousal, the large majority of the variance in subjective arousal was unexplained by desire. A third line of evidence showed no significant difference in levels of subjective arousal to erotic films between sexually functional women and women with desire problems. If desire and subjective arousal were the same construct, then one would expect to see evidence of low subjective arousal in women with low sexual desire. CLINICAL IMPLICATIONS: Optimized treatment efficacy requires differentiating mental and physical factors that contribute to female sexual dysfunction. STRENGTHS AND LIMITATIONS: Support for our conclusion is based on clinical qualitative evidence and quantitative evidence. However, the quantitative support is from only one laboratory at this time. CONCLUSION: These findings strongly support the view that female sexual arousal disorder includes a subjective arousal subtype and that subjective arousal and desire are related but not similar constructs. We advocate for the relevance of maintaining subjective arousal disorder in the diagnostic nomenclature and present several lines of evidence to support this contention. Althof SE, Meston CM, Perelman M, et al. Opinion Paper: On the Diagnosis/Classification of Sexual Arousal Concerns in Women. J Sex Med 2017;14:1365-1371.

Female Sexual Dysfunction-Medical and Psychological Treatments, Committee 14.

INTRODUCTION: Since the millennium we have witnessed significant strides in the science and treatment of female sexual dysfunction (FSD). This forward progress has included (i) the development of new theoretical models to describe healthy and dysfunctional sexual responses in women; (ii) alternative classification strategies of female sexual disorders; (iii) major advances in brain, hormonal, psychological, and interpersonal research focusing on etiologic factors and treatment approaches; (iv) strong and effective public advocacy for FSD; and (v) greater educational awareness of the impact of FSD on the woman and her partner. AIMS: To review the literature and describe the best practices for assessing and treating women with hypoactive sexual desire disorder, female sexual arousal disorder, and female orgasmic disorders. METHODS: The committee undertook a comprehensive review of the literature and discussion among themselves to determine the best assessment and treatment methods. RESULTS: Using a biopsychosocial lens, the committee presents recommendations (with levels of evidence) for assessment and treatment of hypoactive sexual desire disorder, female sexual arousal disorder, and female orgasmic disorders. CONCLUSION: The numerous significant strides in FSD that have occurred since the previous International Consultation of Sexual Medicine publications are reviewed in this article. Although evidence supports an integrated biopsychosocial approach to assessment and treatment of these disorders, the biological and psychological factors are artificially separated for review purposes. We recognize that best outcomes are achieved when all relevant factors are identified and addressed by the clinician and patient working together in concert (the sum is greater than the whole of its parts). Kingsberg SA, Althof S, Simon JA, et al. Female Sexual Dysfunction-Medical and Psychological Treatments, Committee 14. J Sex Med 2017;14:1463-1491.

Diagnosing Sexual Dysfunction in Men and Women: Sexual History Taking and the Role of Symptom Scales and Questionnaires.

INTRODUCTION: A detailed sexual history is the cornerstone for all sexual problem assessments and sexual dysfunction diagnoses. Diagnostic evaluation is based on an in-depth sexual history, including sexual and gender identity and orientation, sexual activity and function, current level of sexual function, overall health and comorbidities, partner relationship and interpersonal factors, and the role of cultural and personal expectations and attitudes. AIM: To propose key steps in the diagnostic evaluation of sexual dysfunctions, with special focus on the use of symptom scales and questionnaires. METHODS: Critical assessment of the current literature by the International Consultation on Sexual Medicine committee. MAIN OUTCOME MEASURES: A revised algorithm for the management of sexual dysfunctions, level of evidence, and recommendation for scales and questionnaires. RESULTS: The International Consultation on Sexual Medicine proposes an updated algorithm for diagnostic evaluation of sexual dysfunction in men and women, with specific recommendations for sexual history taking and diagnostic evaluation. Standardized scales, checklists, and validated questionnaires are additional adjuncts that should be used routinely in sexual problem evaluation. Scales developed for specific patient groups are included. Results of this evaluation are presented with recommendations for clinical and research uses. CONCLUSION: Defined principles, an algorithm and a range of scales may provide coherent and evidence based management for sexual dysfunctions.

Psychometric Evaluation of the Hypogonadism Impact of Symptoms Questionnaire.

INTRODUCTION: The Hypogonadism Impact of Symptoms Questionnaire (HIS-Q) is a patient-reported outcome measurement designed to comprehensively evaluate the symptoms of hypogonadism and to detect changes in these symptoms in response to treatment. AIM: To conduct item analysis and reduction, evaluate the psychometric properties of the HIS-Q, and provide guidance on interpreting the instrument score. METHODS: A 12-week observational, longitudinal study of hypogonadal men was conducted. Participants completed the HIS-Q every 2 weeks. Blood samples were collected to evaluate testosterone levels. Participants also completed the Aging Male's Symptoms Scale, the International Index of Erectile Function, the Short Form-12 Health Survey, and the Patient-Reported Outcomes Measurement Information System Sexual Activity, Satisfaction with Sex Life, Sleep Disturbance, and Applied Cognition Scales (at baseline and weeks 6 and 12). Clinicians completed the Clinical Global Impression of Severity and Change measurements and a clinical form. MAIN OUTCOME MEASURES: Individual item performance was evaluated using descriptive statistics and Rasch analyses. Reliability (internal consistency and test-retest), validity (concurrent and know groups), and responsiveness were assessed. RESULTS: In total, 177 men participated in the study (mean age = 54.1 years, range = 23-83). The original 53-item draft HIS-Q was reduced to 28 items; the final instrument included five domains (sexual, energy, sleep, cognition, and mood) with two sexual subdomains (libido and sexual function). For all domains, test-retest reliability was acceptable (intraclass correlation coefficients > 0.70), construct validity was good (|r > 0.30| for all comparisons). Known-groups validity was demonstrated for all HIS-Q domain scores, subdomain scores, and the total score as measured by the Clinical Global Impression of Severity, and total testosterone level at baseline (P < .05 for all comparisons). All domains and subdomains were responsive to change based on patient-rated anchor questions (P < .05 for all comparisons). CONCLUSION: The final 28-item HIS-Q is reliable, valid, and responsive. The HIS-Q is suitable for inclusion in future clinical trials to help characterize the effects of testosterone replacement therapy.

Toward a More Evidence-Based Nosology and Nomenclature for Female Sexual Dysfunctions-Part II.

INTRODUCTION: Current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) definitions of sexual dysfunction do not identify all sexual problems experienced clinically by women and are not necessarily applicable for biologic or biopsychosocial management of female sexual dysfunction. A unified nomenclature system enables clinicians, researchers, and regulatory agencies to use the same language and criteria for determining clinical end points, assessing research results, and managing patients. AIM: To develop nomenclature with classification systems for female sexual desire, arousal, and orgasm disorders with definitions pertinent to clinicians and researchers from multiple specialties who contribute to the field of sexual medicine. METHODS: Key national and international opinion leaders diverse in gender, geography, and areas of expertise met for 2 days to discuss and agree to definitions of female sexual desire, arousal, and orgasm disorders and persistent genital arousal disorder. The attendees consisted of 10 psychiatrists and psychologists; 12 health care providers in specialties such as gynecology, internal medicine, and sexual medicine; three basic scientists; and one sexuality educator, representing an array of societies working within the various areas of sexual function and dysfunction. MAIN OUTCOME MEASURE: A unified set of definitions was developed and accepted for use by the International Society for the Study of Women's Sexual Health (ISSWSH) and members of other stakeholder societies participating in the consensus meeting. RESULTS: Current DSM-5 definitions, in particular elimination of desire and arousal disorders as separate diagnoses and lack of definitions of other specific disorders, were adapted to create ISSWSH consensus nomenclature for distressing sexual dysfunctions. The ISSWSH definitions include hypoactive sexual desire disorder, female genital arousal disorder, persistent genital arousal disorder, female orgasmic disorder, pleasure dissociative orgasm disorder, and female orgasmic illness syndrome. CONCLUSION: Definitions for female sexual dysfunctions that reflect current science provide useful nomenclature for current and future management of women with sexual disorders and development of new therapies.

Clinical and Demographic Correlates of Ejaculatory Dysfunctions Other Than Premature Ejaculation: A Prospective, Observational Study.

INTRODUCTION: Ejaculatory dysfunctions other than premature ejaculation are commonly encountered in specialized clinics; however, their characterization in community-dwelling men is lacking. AIM: The aim of this study was to evaluate the prevalence, severity, and associated distress of four ejaculatory dysfunctions: delayed ejaculation (DE), anejaculation (AE), perceived ejaculate volume reduction (PEVR) and/or decreased force of ejaculation (DFE) as a function of demographic and clinical characteristics in men. METHODS: Observational analysis of 988 subjects presenting with one or more types of ejaculatory dysfunctions other than premature ejaculation who screened for a randomized clinical trial assessing the efficacy of testosterone replacement on ejaculatory dysfunction. Demographic and clinical characteristics were assessed as potential risk factors using regression analysis. MAIN OUTCOME MEASURES: The main outcome measures used were ejaculatory dysfunction prevalence and scores (3-item Men's Sexual Health Questionnaire Ejaculatory Dysfunction-Short Form [MSHQ-EjD-SF]), and bother (MSHQ-EjD-SF Bother item) and sexual satisfaction/enjoyment (International Index of Erectile Function Questionnaire Q7, Q8) as a function of subject's age, race, body mass index (BMI) and serum testosterone levels (measured by liquid chromatography tandem mass spectrometry). RESULTS: Mean (standard deviation [SD]) age of the participants was 52 years (11). Eighty-eight percent of the men experienced more than one type of ejaculatory dysfunction and 68% considered their symptoms to be bothersome. Prevalence of the ejaculatory dysfunctions was substantial across a range of age, race, BMI, and serum testosterone categories. Prevalence of PEVR and DFE were positively associated with age (<40 years vs. 60-70 years: PEVR: odds ratio [OR], 3.05; 95% confidence interval [CI], 1.32-7.06; DFE: OR, 2.78; 95% CI, 1.46-5.28) while DFE was associated with BMI (≥30 kg/m(2) vs. < 25 kg/m(2) : OR, 1.80; 95% CI, 1.062-3.05). All ejaculatory dysfunctions were more prevalent in black men. CONCLUSION: The majority of the participants experienced multiple ejaculatory dysfunctions and found them to be highly bothersome. Ejaculatory dysfunctions were prevalent across a wide range of demographic and clinical characteristics.

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.