Satisfying Sexual Events Research Articles

Role of flibanserin in managing hypoactive sexual desire disorder in women: A systematic review and meta-analysis.

Flibanserin, approved for the treatment of hypoactive sexual desire disorder (HSDD) in females, has demonstrated diverse therapeutic and adverse effect (AE) prospects in the extant randomized controlled trials (RCTs). This meta-analysis aimed to characterize the outcomes of flibanserin use in these patients comprehensively. RCTs involving women with HSDD receiving flibanserin in the intervention arm and placebo in the control arm were sought after throughout the electronic databases. The primary outcomes were the changes from baseline in satisfying sexual events (SSE) per month and sexual desire score per month measured using an electronic diary (eDiary). From 478 initially screened articles, data from 8 RCTs involving 7906 women with HSDD were analyzed. In premenopausal women, flibanserin 100 mg was superior to placebo in improving the number of SSE per month (mean difference, MD 0.69, 95% CI [0.39, 0.99]), eDiary sexual desire score (MD 1.71, 95% CI [0.43, 2.98]), Female Sexual Function Index (FSFI) desire domain (FSFI-d) score (MD 0.30, 95% CI [0.29, 0.31]), FSFI total score (MD 2.51, 95% CI [1.47, 3.55]), Female Sexual Distress Scale-Revised (FSDS-R) Item 13 score (MD -0.30, 95% CI [-0.31, -0.29]), and FSDS-R total score (MD -3.30, 95% CI [-3.37, -3.23]). Compared to placebo, a higher number of premenopausal women using flibanserin 100 mg achieved improvements in the Patient's Global Impression of Improvement score (OR 1.93, 95% CI [1.58, 2.36], P < .00001) and responded positively at Patient Benefit Evaluation (PBE) (odds ratio, OR 1.76, 95% CI [1.34, 2.31], P < .0001). Postmenopausal women receiving flibanserin 100 mg also benefited in terms of the number of SSE per month, FSFI-d and total scores, FSDS-R Item 13 and total scores, and PBE response. Although flibanserin use was associated with higher risks of dizziness, fatigue, nausea, somnolence, and insomnia, these adverse events were mild in nature; the serious AEs and severe AEs were comparable between the flibanserin and placebo groups. While flibanserin has demonstrated efficacy in the treatment of HSDD in both pre- and postmenopausal women, its therapeutic advantages may be overshadowed by the higher likelihood of AEs.

(215) Design of the ALETTA Clinical Study: A Randomized Double-Blind Placebo-Controlled Study investigating the Efficacy and Safety of LybridoTM in Premenopausal Women with Acquired FSIAD

Abstract Introduction Low sexual desire is the most common sexual complaint in women. As a result, many women suffer from sexual dissatisfaction and related distress which often negatively interferes with their quality of life. Currently, limited drug treatments are available globally to treat women with Hypoactive Sexual Desire Disorder/Female Sexual Interest &amp; Arousal Disorder (FSIAD). Consequently, there is an unmet need, and relevance to developing a drug treatment for women with sexual dysfunction. LybridoTM is a novel on-demand dual-route/dual release fixed-dose combination tablet of sublingual testosterone and oral sildenafil, with the aim to synergistically enhance both central and peripheral processes. It has shown a promising efficacy and safety profile in Phase 2 and is ready for Phase 3 testing. Objective Description of a study design to evaluate two-dose strength and compared to placebo for the treatment of FSIAD Methods A double-blind, randomized, placebo-controlled, 3-arm, 6-month study to evaluate the efficacy and safety of LybridoTM in premenopausal women with acquired FSIAD. An interim analysis will be performed and overseen by an independent Data Monitoring Committee, to re-estimate the sample size according to predefined criteria. Study Population: European premenopausal women, at least 18 years of age, with a clinical diagnosis of acquired FSIAD. Study Duration: Up to 4-week screening period, followed by a 4-week wash-out baseline period, 24-week treatment period, and 4-week safety follow-up period. Interventions: The study drug is a fixed-dose combination tablet consisting of an inner core containing sildenafil with an outer delayed immediate release coating and an additional outer film coating containing testosterone. Two dose strengths will be evaluated and compared with a placebo. Results Primary endpoint: change from baseline to Week 24 in sexual desire assessed by Female Sexual Function Index Desire Domain (FSFI-D) (Items 1 and 2). Secondary efficacy endpoints: sexual distress assessed by Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) score for Item 13; Elements of Desire Questionnaire (EDQ) ‘event-based’ (ie, within 24 hours of a sexual or dosing event); sexual arousal assessed by FSFI Arousal Domain (FSFI-A); sexual function assessed by FSFI total score; sexual distress assessed by FSDS-DOA total score; the number of satisfying sexual events (SSEs) using the Sexual Satisfaction of an Event Questionnaire (SSEQ), reported within 24 hours and assessed relative to the total number of sexual events; patient-reported impression of improvement assessed by the Patient Global Impression of Improvement (PGI-I) Scale; patient-reported impression of severity assessed by the Patient Global Impression of Severity (PGI-S) Scale; and the total number of sexual events. Safety outcomes: frequency of (serious) adverse events. Conclusions First Patient In: Q1 2023; Interim Analysis: Q4 2023; Last Patient Out: Q2 2024. Disclosure Yes, this is sponsored by industry/sponsor: Freya Clarification Industry initiated, executed and funded study Any of the authors act as a consultant, employee or shareholder of an industry for: Freya

Flibanserin Improves Libido In Women with Breast Cancer

ABSTRACT Introduction Sexual dysfunction is reported during and after breast cancer treatment and causes a substantial distress on women. Breast cancer and its treatment can cause decreased libido and there are currently no FDA approved medications for the treatment of disease and/or medication induced hyposexual desire disorder (HSDD). This study evaluates the use of flibanserin in breast cancer patients on endocrine therapy who are experiencing decreased libido. Objective The primary endpoint of this study is to evaluate the feasibility of flibanserin for 24 weeks in women with breast cancer on endocrine therapy. Secondary endpoints include efficacy of flibanserin as measured by the number of satisfying sexual events (SSE) per month, change in desire, change in sexual function, QoL and distress from sexual function. These outcomes are measured using a pill diary and these validated instruments: Female Sexual Function Index (FSFI) both desire and total scores, Female Sexual Distress Scale (FSDS-R), and Patient-reported Outcomes Measurement Information System Sexual Function Instrument (PROMIS-SF). Methods Twenty women with stage 0-III ER+ breast cancer on endocrine therapy for at least three months were enrolled from both an academic center and an alliance community site on a prospective, longitudinal pilot IRB-approved trial to evaluate the feasibility and efficacy of flibanserin in women with breast cancer on endocrine therapy. All patients met criteria for the diagnosis of HSDD as defined by the DSM-IV and ISSWSH consensus paper. Patients took flibanserin 100mg po at bedtime for 24 weeks and were followed for 52 weeks. Patients were monitored closely with medical exams including vital signs and completed questionnaires at baseline, weeks 4, 8, 16, 24 and 52. Given the small sample size, descriptive, graphical, and nonparametric paired tests for pairwise comparisons of a measure were performed. Results This study met its pre-defined feasibility end point. We found more than 70% of the study patients were able to complete 24 weeks of flibanserin therapy and took greater than 80% of planned doses of flibanserin as documented in their medication diary. Three patients dropped out of the study within 14 days of starting the medication due to adverse side effects. Our study also found patients subjectively reported improved libido through PROs and SSEs. The baseline mean FSFI total score was 13.3 with a desire score of 1.96 and improved to a total score of 19.4 and desire score of 3.3 by 8 weeks on flibanserin. All study participants except one reported 0 sexually satisfying events per month at baseline and this increased to 2.2 per month after 8 weeks of treatment. Patient distress also decreased from 32 to 25 on the FSDS-R and 3.33 to 2.86 on the distress thermometer at 8 weeks. Conclusions It is feasible for women with breast cancer on endocrine therapy with HSDD to take flibanserin for 24 weeks. The majority of women reported efficacy from the medication with increased libido as measured by the FSFI, increased SSEs and decreased distress. Flibanserin improved patients’ overall sexual functioning. A larger randomized placebo-controlled study is still needed to further evaluate flibanserin in women with breast cancer. Disclosure Yes, this is sponsored by industry/sponsor: The study is funded by a research grant through Sprout Pharmaceuticals Inc Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Consulting and Advisory Boards for NanOlogy, Spectrum Pharmaceuticals Inc, Sermonix Pharmaceuticals LLC, Procter &amp; Gamble and Paxman Coolers Limited

The beneficial effect of short-term multimodal physiological therapy on female provoked vulvodynia: A pilot study

ABSTRACT Introduction Vulvodynia is a subset of the genito-pelvic/penetration disorder and is currently defined by chronic pain in the vulva area of at least 3-6 months duration. It affects 8-10% of women of all ages. According to 2015 ISSVD, ISSWSH, and IPPS consensus terminology and classification of vulvodynia, it can be divided into provoked (e.g., insertional, contact), spontaneous or mixed type. Although the etiology remains an enigma, peripheral neurologic mechanism has recently been identified as a factor. Objective The aim of this trial was to evaluate the effectiveness of short-term physical therapy in women with vulvodynia. Methods Women with intolerable vulvodynia were included in the study from Jan to May 2021. Medical screen including cotton-tipped testing and pelvic examination were performed by one gynecologist. After informed consent obtained, women lied down with cross-legged receiving once treatment per 1-2 weeks until completely pain relief achieved. Treatment consisted of a multimodal approach including lidocaine gel 20mins, capsaicin gel 20mins and TENS (Transcutaneous electrical nerve stimulator) 30 mins. TENS was administered through skin probes via a dual channel NeuroTrac device. A set of double electrode patches were placed on the dermatome of unilateral side of pain: channel A constant 80Hz, and channel B burst of 9 pulses 150Hz, 175 µS pulse duration and the intensity at the maximal level that patient could tolerate. At the completion, all women were followed for 3-6 months to assess efficacy, satisfying sexual events (SSE) in 4weeks, adverse events and recurrence. Results Ten women were diagnosed with provoked (n=8) or spontaneous vulvodynia (n=2) (primary 60% and secondary 40%). The average age was 34.1 years (range= 25-50) with an average duration of vulvodynia of 50.0 months (range= 4-276). 50% of women reported tolerating intercourse sometimes, 40% never did, and one was virgin. 37.5% (n=3) underwent one treatment session, and 62.5% (n=5) two sessions to achieve completely pain relief. At the completion of one week, 100% of provoked type women reported moderate or high improvement on vulvodynia region. Those reported improvement in the frequency of SSE within 4 weeks after treatment completion (62.5% sometimes, 25% often and one didn't restart intercourse). However, both of spontaneous type women failed to treatment and were suggested a referral for nerve blocking. After 4.4-24.3 weeks follow-up, 25% of provoked group reported no recurrence, 62.5% mild recurrence, and 12.5% (n=1) moderate recurrence. Only minor adverse events occurred. 90% reported mild to moderate vulva irritation immediately after treatment, which were completely resolved after bath. Only one spontaneous type reported vulva swelling and moderate irritation for one week. 100% of participants were willing to receive treatment in the next time. Conclusions A short-term multimodal physiological therapy including lidocaine, capsaicin and TENS enabled women with provoked vulvodynia to achieve rapid pain relief, moderate or high improvement in sexual encounters and the efficacy is seemed to last long. The tolerability and safety were high. Disclosure Work supported by industry: no. A consultant, employee (part time or full time) or shareholder is among the authors (Youren clinic).

Clinically Meaningful Benefit in Women with Hypoactive Sexual Desire Disorder Treated with Flibanserin.

BackgroundThe efficacy of flibanserin in treating hypoactive sexual desire disorder (HSDD) is based upon statistically significant improvements in sexual desire, satisfying sexual events, and distress. However, clinically meaningful benefit has not been well characterized.AimEvaluate clinically meaningful benefit of flibanserin.MethodsData were pooled from 3 pivotal trials evaluating flibanserin 100 mg qhs in premenopausal women (flibanserin, n = 1192; placebo, n = 1215). Flibanserin trial data in postmenopausal women (flibanserin, n = 450; placebo, n = 476) were analyzed separately. Clinically meaningful benefit was evaluated by the Patient Global Impression of Improvement (PGI-I). Responders were determined through anchor-based analyses that used the PGI-I for key efficacy endpoints: satisfying sexual events (SSE), desire domain of the Female Sexual Function Index (FSFI-d), and distress associated with decreased sexual desire (FSDS-R13). Odds ratios were calculated to assess effect size and Kaplan-Meier analyses were performed to estimate onset time for treatment benefit.OutcomesPGI-I, anchor-based analyses for key efficacy endpoints (SSE, FSFI-d, FSDS-R13), odds ratios, onset time for treatment benefit.ResultsBased on the PGI-I, more patients reported clinically meaningful benefit with flibanserin treatment versus placebo (49.8% vs 33.6%, premenopausal cohort; 40.5% vs 28.7%, postmenopausal cohort). In anchor-based analyses, responder rates were significantly higher for premenopausal women on flibanserin (46.1%–55.2%) than placebo (34.1%–44.2%) for all 3 key efficacy endpoints (P < .0001). Responder rates for postmenopausal women on flibanserin were higher compared to placebo for SSE (29.8% vs 22.9%; P = .015) and FSFI-d (38.9% vs 26.3%; P = .0001). Odds ratios for key endpoints indicated that premenopausal women were 2.0–2.4 times as likely to be responders with flibanserin treatment compared to placebo. Postmenopausal women were 1.6 times as likely to be responders with flibanserin for FSFI-d. Kaplan-Meier analyses indicated significant separation between flibanserin and placebo for the key endpoints in both premenopausal and postmenopausal cohorts (log-rank tests P < .01) with earlier median response times among patients receiving flibanserin.Clinical ImplicationsPatient-reported benefit assessments such as the PGI-I capture the patient's perspective and may be a useful approach in assessing overall clinical meaningfulness for sexual dysfunction therapies.Strengths and LimitationsStrengths include a well-powered study with large enrollment, use of validated instruments, and self-assessment of treatment benefit. Limitations include pooling of trial data in premenopausal women with slightly different study designs and use of an endpoint (SSE) indirectly related to HSDD.ConclusionAssessment of clinically meaningful benefit and additional responder analyses provide further support for flibanserin's efficacy beyond numerical improvements in endpoint measures.Simon JA, Clayton AH, Kim NN, et al. Clinically Meaningful Benefit in Women with Hypoactive Sexual Desire Disorder Treated with Flibanserin. Sex Med 2022;10:100476.

Flibanserin for Premenopausal Hypoactive Sexual Desire Disorder: Pooled Analysis of Clinical Trials.

Background: Flibanserin, a 5-hydroxytryptamine 5-HT1A agonist and 5-HT2A antagonist, is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This post hoc analysis assessed pooled efficacy and safety data for flibanserin in premenopausal women with HSDD. Materials and Methods: Data for flibanserin 100 mg once daily at bedtime (qhs) and placebo were pooled from three pivotal 24-week, randomized, placebo-controlled, multicenter studies (VIOLET, DAISY, and BEGONIA) of premenopausal women with HSDD. Pooled efficacy endpoints included the change from baseline to study end (i.e., 24 weeks) in the number of satisfying sexual events (SSEs) over 28 days, the Female Sexual Function Index desire domain (FSFI-d) score, and the Female Sexual Distress Scale-Revised Item 13 (FSDS-R-13) score. Results: The analysis included 2465 women (flibanserin, n = 1227; placebo, n = 1238) with a mean age of 36 years and a mean HSDD duration of 56.5 months. The mean ± standard error (SE) change from baseline to study end in SSEs over 28 days for flibanserin versus placebo was 2.1 ± 0.14 versus 1.2 ± 0.11, respectively (p < 0.0001). The least-squares mean ± SE changes from baseline to study end in FSFI desire domain score and FSDS-R-13 score were also significantly greater for flibanserin versus placebo (FSFI desire domain: 0.9 ± 0.04 vs. 0.6 ± 0.04, p < 0.0001; FSDS-R-13: -0.9 ± 0.04 vs. -0.6 ± 0.04, p < 0.0001). Patients in the flibanserin group generally had significantly greater improvements, compared with placebo, in SSEs, FSFI-d score, and FSDS-R-13 in subgroup analyses based on selected demographic and baseline clinical characteristics. Adverse events occurring in ≥10% of patients included dizziness and somnolence. Conclusions: This pooled analysis of three pivotal trials demonstrated that flibanserin 100 mg qhs was well tolerated, improved sexual desire, and reduced sexual distress associated with HSDD in premenopausal women, and these improvements were generally consistent across various subgroups based on demographic and baseline characteristics.

341 Mercy Sex: How Much Is “Normal”

Women engage in sexual relations despite the absence of personal interest. Such sexual activity has been termed: duty sex, obligatory sex, or mercy sex. Over the past two decades medical treatments for hypoactive sexual desire disorder (HSDD; DSM-IV-TR) have investigated thousands of women. Women entering these HSDD clinical trials continue to have sexual relations with their partners despite their HSDD. Here we quantify the “normal” frequency of sexual activity (without interest), aka “mercy sex” in these trial participants. Data were analyzed from published clinical trials of the Intrinsa® (transdermal testosterone patch; surgically menopausal women on estrogen therapy [Intimate SM 1, SM 2], not on estrogen therapy [Aphrodite]), Addyi® (flibanserin; premenopausal women [Daisy, Begonia] on or off oral contraceptives, and menopausal [Snowdrop], on or off estrogen or hormone therapy), clinical developments. The number of satisfying sexual events (SSEs) reported at baseline were tabulated and analyzed. The mean number of satisfying sexual events (SSEs) per 28 days is reported in the table below.

015 Efficacy of Flibanserin by Duration of Hypoactive Sexual Desire Disorder in Premenopausal Women

Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This post hoc analysis evaluated the efficacy of flibanserin treatment by duration of HSDD. Data were pooled from three 24-week, double-blind, placebo-controlled studies of flibanserin in premenopausal women with HSDD. Patients were stratified by HSDD duration (>6 months to 2 years, >2-5 years, and >5 years). Key measures of efficacy were the Female Sexual Function Index desire domain (FSFI-d) score, the Female Sexual Distress Scale-Revised item 13 (distress due to low desire; FSDS-R-13) score, and the number of satisfying sexual events (SSE). This analysis included 2344 premenopausal women (HSDD duration >6 months to 2 years, n=705; duration >2-5 years, n=830; duration >5 years, n=809) who received flibanserin 100 mg qhs or placebo. Improvement from baseline to week 24 in FSFI-d score (least-squares [LS] mean change) was significantly greater for flibanserin compared with placebo in women with HSDD for >6 months to 2 years (1.0 vs 0.8; P=0.010), >2-5 years (0.9 vs 0.6; P=0.004), and >5 years (0.9 vs 0.5; P<0.0001). Similarly, significantly greater improvement on the FSDS-R-13 (LS mean change) for flibanserin versus placebo was observed in women with HSDD duration of >6 months to 2 years (-1.0 vs -0.7; P=0.017), >2-5 years (-0.8 vs -0.6; P=0.027), and >5 years (-0.8 vs -0.5; P<0.0001) For SSE, improvement (LS mean change) with flibanserin relative to placebo was significantly different for HSDD duration >6 months to 2 years (2.7 vs 1.6; P=0.018) and duration >5 years (1.9 vs 1.2, P=0.003), but did not reach statistical significance, though trended, for duration of >2-5 years (1.9 vs 1.3; P=0.053). The most common adverse events associated with flibanserin (>5% of flibanserin-treated patients, overall) were somnolence (12.8% for flibanserin vs 3.4% for placebo) and dizziness (10.6% vs 1.5%).

Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials

BackgroundIn women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available. AimTo investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups. Methods497 women (21–70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T; 0.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mg + S 25 mg, T 0.25 mg + S 50 mg, T 0.5 mg + S 25 mg, T 0.5 mg + S 50 mg, and T 0.25 mg + B 5 mg, T 0.25 mg + B 10 mg, T 0.5 mg + B 5 mg, T 0.5 mg + B 10 mg). OutcomesThe primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure. ResultsIn women with low sensitivity for sexual cues, 0.5 mg T + 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ] = 1.70, 95% CI = 0.57–2.84, P = .004) and monotherapies (S: Δ = 1.95, 95% CI = 0.44–3.45, P = .012; T: Δ = 1.69, 95% CI = 0.58–2.80, P = .003). In women with overactive inhibition, 0.5 mg T + 10 mg B increased the number of SSEs from baseline compared with placebo (Δ = 0.99, 95% CI = 0.17–1.82, P = .019) and monotherapies (B: Δ = 1.52, 95% CI = 0.57–2.46, P = .002; T: Δ = 0.98, 95% CI = 0.17–1.78, P = .018). Secondary end points followed this pattern of results. The most common drug-related side effects were flushing (T + S treatment, 3%; T + B treatment, 2%), headache (placebo treatment, 2%; T + S treatment, 9%), dizziness (T + B treatment, 3%), and nausea (T + S treatment, 3%; T + B treatment, 2%). Clinical ImplicationsT + S and T + B are promising treatments for women with FSIAD. Strengths and LimitationsThe data were collected in 3 well-designed randomized clinical trials that tested multiple doses in a substantial number of women. The influence of T + S and T + B on distress and the potentially sustained improvements after medication cessation were not investigated. ConclusionsT + S and T + B are well tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups.Tuiten A, van Rooij K, Bloemers J, et al. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials. J Sex Med 2018;15:201–216.

What Sexual Behaviors Relate to Decreased Sexual Desire in Women? A Review and Proposal for End Points in Treatment Trials for Hypoactive Sexual Desire Disorder.

IntroductionCounts of satisfying sexual events (SSEs) per month have been criticized as an end point in treatment trials of women with hypoactive sexual desire disorder (HSDD) but grounding improvement in sexual desire by assessing changes in sexual behavior remains of some importance.MethodsWe conducted a literature review to find validated measurements that are specific sexual behavioral correlates of low sexual desire. We compared expert-proposed criteria for dysfunctional desire, expert-developed sets of scale items, and self-rated scales developed before issuance of, or in accordance with, the Food and Drug Administration’s guidance on developing patient-reported outcomes. Behavioral measurements of HSDD were isolated from these sets of criteria or scales.Main Outcome MeasuresWe outline a plan to evaluate such behavioral measurements of HSDD with reference to SSEs.ResultsEleven rating scales, four expert-originated and seven self-rated scales mainly derived from patient input were identified as well validated and relevant to HSDD. Three recent sets of diagnostic criteria for conditions such as HSDD were compared with the scales. Twenty-four different symptoms were found in the scales. Content found relevant to HSDD during development of the rating scales varied highly among measurements, including the self-rated scales developed in conformity with current recommendations for patient-reported outcome measurements. The only item on all sets was desire for sexual activity. Four other items were in approximately at least half the sets: sexual thoughts or fantasies, frequency of sexual activity, receptivity, and initiations. Sexual thoughts or fantasies were in every expert-derived set but in only three of the seven patient-derived sets. Receptivity was in five of the seven expert-derived sets vs two of the seven patient-derived sets. Frequency of sexual activity was in one of the seven expert-derived sets but in five of the patient-derived sets. Initiation was in approximately half the two sets. All other items were on one to three sets each. We identified three sexual behaviors of validated specificity for female HSDD: frequency of sexual activity, receptivity, and initiations. Six or seven items are relevant and informative. The item on frequency of sexual activity in the Changes in Sexual Functioning–Female scale is the only item that covers frequency of dyadic and solitary sexual activity. An item in the Female Sexual Desire Questionnaire (FSDQ) covers the intuitively relevant topic of frequency of sexual activity motivated by the woman’s desire. Three FSDQ items on initiations and two items on receptivity reflect expert opinion on the sexual behaviors of most relevance to HSDD, but the FSDQ has not been validated in women with HSDD.ConclusionsSSEs have been discredited as the primary measurement in clinical trials of women with HSDD, but it would be meaningful to include at least one sexual behavioral symptom specific to HSDD as an end point. Expert-recommended sexual behaviors specifically related to HSDD are irregularly represented in self-rating scales whether developed as in the Food and Drug Administration guidance on patient-reported outcomes or not. Six or seven items on sexual behavior in self-rated scales can be recommended for relevance to women with HSDD in clinical trials. Items on female sexual behavior should be tested in comparison with SSEs in women with HSDD for relevance and for treatment sensitivity, and responder and functional and dysfunctional cutoffs should be determined before incorporation into large-scale clinical trials.Pyke R and Clayton A. What Sexual Behaviors Relate to Decreased Sexual Desire in Women? A Review and Proposal for End Points in Treatment Trials for Hypoactive Sexual Desire Disorder. Sex Med 2017;5:e73–e83.

Standards in Studies of Psychotherapy and Pharmacotherapy Interventions for HSDD

It is unfortunate that Brotto, Basson, and colleagues began their paper with a criticism of the efficacy of flibanserin as measured by satisfying sexual events (SSEs) when essentially all researche...

082 Responder Analyses Based on Minimum Clinically Important Differences Derived from Receiver Operating Characteristic Curves in Premenopausal Women Using Bremelanotide for Female Sexual Dysfunctions

Bremelanotide (BMT) is a novel cyclic heptapeptide known to act as a melanocortin-receptor-4 agonist. In a large Phase 2 study of its potential use to treat female sexual dysfunctions (FSDs), key efficacy outcomes were subjected to post hoc responder analyses anchored to minimum clinically important differences (MCIDs) derived from receiver operating characteristic (ROC) curves. All patients were premenopausal women with hypoactive sexual desire disorder and/or female sexual arousal disorder. After 4 weeks of single-blinded subcutaneous (SC) placebo self-dosing (baseline period), they were randomized to double-blind SC placebo or BMT 0.75, 1.25, or 1.75 mg for 12 weeks of at-home, as-needed self-dosing. Key efficacy endpoints included change from baseline to end of study (EOS) in the 4-week number of satisfying sexual events (SSEs) and in total score and desire subscore on the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale–Desire/Arousal/Orgasm (FSDS-DAO). At EOS, patients responded, on a 7-point Likert scale, to a questionnaire item asking: “To what degree do you think you benefited from taking the study drug?” From a ROC curve for each efficacy endpoint, an MCID was computed as the value simultaneously maximizing the endpoint’s sensitivity and specificity for predicting a Likert-scale rating of 5 to 7 (i.e., patient-reported global benefit). The MCIDs then served as anchors for responder analyses.

Efficacy and Safety of Flibanserin for the Treatment of Hypoactive Sexual Desire Disorder in Women: A Systematic Review and Meta-analysis.

In August 2015, the US Food and Drug Administration (FDA) approved flibanserin as a treatment for hypoactive sexual desire disorder (HSDD) in premenopausal women, despite concern about suboptimal risk-benefit trade-offs. To conduct a systematic review and meta-analysis of randomized clinical trials assessing efficacy and safety of flibanserin for the treatment of HSDD in women. Medical databases (among others, Embase, Medline, Psycinfo) and trial registries were searched from inception to June 17, 2015. Reference lists of retrieved studies were searched for additional publications. Randomized clinical trials assessing treatment effects of flibanserin in premenopausal and postmenopausal women were eligible. No age, language, or date restrictions were applied. Abstract and full-text selection was done by 2 independent reviewers. Data were extracted by one reviewer and checked by a second reviewer. Results were pooled using 2 approaches depending on the blinding risk of bias. Primary efficacy outcomes included number of satisfying sexual events (SSEs), eDiary sexual desire, and Female Sexual Function Index (FSFI) desire. Safety outcomes included, among others, 4 common adverse events (AEs): dizziness, somnolence, nausea, and fatigue. Five published and 3 unpublished studies including 5914 women were included. Pooled mean differences for SSE change from baseline were 0.49 (95% CI, 0.32-0.67) between 100-mg flibanserin and placebo, 1.63 (95% CI, 0.45-2.82) for eDiary desire, and 0.27 (95% CI, 0.17-0.38) for FSFI desire. The risk ratio for study discontinuation due to AEs was 2.19 (95% CI, 1.50-3.20). The risk ratio for dizziness was 4.00 (95% CI, 2.56-6.27) in flibanserin vs placebo, 3.97 (95% CI, 3.01-5.24) for somnolence, 2.35 (95% CI, 1.85-2.98) for nausea, and 1.64 (95% CI, 1.27-2.13) for fatigue. Women's mean global impression of improvement scores indicated minimal improvement to no change. Treatment with flibanserin, on average, resulted in one-half additional SSE per month while statistically and clinically significantly increasing the risk of dizziness, somnolence, nausea, and fatigue. Overall, the quality of the evidence was graded as very low. Before flibanserin can be recommended in guidelines and clinical practice, future studies should include women from diverse populations, particularly women with comorbidities, medication use, and surgical menopause.

Efficacy and safety of flibanserin in postmenopausal women with hypoactive sexual desire disorder

This study aimed to assess the efficacy and safety of flibanserin, a serotonin receptor 1A agonist/serotonin receptor 2A antagonist, in postmenopausal women with hypoactive sexual desire disorder (HSDD). Naturally postmenopausal women with HSDD received flibanserin 100 mg once daily at bedtime (n = 468) or placebo (n = 481) for 24 weeks. Co-primary endpoints were changes from baseline to week 24 in the number of satisfying sexual events (SSEs) across 28 days and in the Female Sexual Function Index (FSFI) desire domain score. Secondary endpoints included change from baseline in Female Sexual Distress Scale-Revised (FSDS-R) Item 13 score (which assesses distress due to low sexual desire), FSDS-R total score, and FSFI total score. The Patient Benefit Evaluation was asked on treatment discontinuation. There were significant improvements with flibanserin versus placebo in the mean (SE) changes in the number of SSEs (1.0 [0.1] vs 0.6 [0.1]), FSFI desire domain score (0.7 [0.1] vs 0.4 [0.1]), FSDS-R Item 13 score (-0.8 [0.1] vs -0.6 [0.1]), FSDS-R total score (-8.3 [0.6] vs -6.3 [0.6]), and FSFI total score (4.2 [0.4] vs 2.7 [0.4]; all P < 0.01). More women on flibanserin (37.6%) than women on placebo (28.0%) reported experiencing meaningful benefits from the study medication on treatment discontinuation. The most frequent adverse events associated with flibanserin were dizziness, somnolence, nausea, and headache. In naturally postmenopausal women with HSDD, flibanserin, compared with placebo, has been associated with improvement in sexual desire, improvement in the number of SSEs, and reduced distress associated with low sexual desire, and is well tolerated.

Efficacy of Flibanserin in Women with Hypoactive Sexual Desire Disorder: Results from the BEGONIA Trial

Hypoactive Sexual Desire Disorder (HSDD) is characterized by low sexual desire that causes marked distress or interpersonal difficulty. The aim of this study was to assess the efficacy and safety of the 5-HT1A agonist/5-HT2A antagonist flibanserin in premenopausal women with HSDD. This was a randomized, placebo-controlled trial in which premenopausal women with HSDD (mean age: 36.6 years) were treated with flibanserin 100 mg once daily at bedtime (qhs) (n = 542) or placebo (n = 545) for 24 weeks. Coprimary end points were the change from baseline to study end in Female Sexual Function Index (FSFI) desire domain score and in number of satisfying sexual events (SSE) over 28 days. Secondary end points included the change from baseline in FSFI total score, Female Sexual Distress Scale-Revised (FSDS-R) total score, and FSDS-R Item 13 score. Compared with placebo, flibanserin led to increases in mean (standard deviation) SSE of 2.5 (4.6) vs. 1.5 (4.5), mean (standard error [SE]) FSFI desire domain score of 1.0 (0.1) vs. 0.7 (0.1), and mean (SE) FSFI total score of 5.3 (0.3) vs. 3.5 (0.3); and decreases in mean (SE) FSDS-R Item 13 score of -1.0 (0.1) vs. -0.7 (0.1) and mean (SE) FSDS-R total score of -9.4 (0.6) vs. -6.1 (0.6); all P ≤ 0.0001. The most frequently reported adverse events in the flibanserin group were somnolence, dizziness, and nausea, with adverse events leading to discontinuation in 9.6% of women receiving flibanserin vs. 3.7% on placebo. In premenopausal women with HSDD, flibanserin 100 mg qhs resulted in significant improvements in the number of SSE and sexual desire (FSFI desire domain score) vs. placebo. Flibanserin was associated with significant reductions in distress associated with sexual dysfunction (FSDS-R total score) and distress associated with low sexual desire (FSDS-R Item 13) vs. placebo. There were no significant safety concerns associated with the use of flibanserin for 24 weeks.

Intended or Unintended Consequences? The Likely Implications of Raising the Bar for Sexual Dysfunction Diagnosis in the Proposed DSM‐V Revisions: 2. For Women with Loss of Subjective Sexual Arousal

Brotto proposes to combine female sexual desire and arousal disorders in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. We provide evidence that the proposed criteria could potentially exclude from diagnosis or treatment a large number of women with distressing dysfunction in sexual arousal. Rating scale data from nontreatment validation studies of patient-reported outcome measures including almost 500 women in North America and Europe, including 49 women diagnosed with arousal disorder only, were compared with the proposed criteria. The main measures were an early version of the eDiary (an electronic diary on sexual activity) and four previously validated measures of female sexual dysfunction (FSD), the clinician-rated Sexual Interest and Desire Inventory-Female and the self-rated Female Sexual Function Index, Changes in Sexual Functioning Questionnaire, and Female Sexual Distress Scale. Results. The women with female sexual arousal disorder (FSAD) scored as manifestly sexually dysfunctional and significantly sexually distressed. They had fewer satisfying sexual events (SSEs) vs. women with no FSD, with a lower proportion of SSEs, and significantly fewer orgasms. Despite evidence presented that women with FSAD have clinically disordered sexual function, our data also suggest that the majority of these women with FSAD would meet none of the six proposed "A" criteria for Sexual Interest/Arousal Disorder, raising new validity and utility concerns for the proposed diagnostic classification. Suggestions are made to modify the proposed new criteria so as to include such distressed women.

Treatment of Hypoactive Sexual Desire Disorder in Premenopausal Women: Efficacy of Flibanserin in the VIOLET Study

Hypoactive sexual desire disorder (HSDD) is the most common form of female sexual dysfunction and is characterized by low sexual desire that causes distress. The aim of this study was to assess the efficacy and safety of flibanserin, a postsynaptic 5-HT(1A) agonist/5-HT(2A) antagonist, in premenopausal women with HSDD. North American premenopausal women with HSDD were randomized to 24 weeks' treatment with placebo (N = 295), flibanserin 50 mg (N = 295), or flibanserin 100 mg (N = 290), once daily at bedtime. Coprimary endpoints were change from baseline to study end in number of satisfying sexual events (SSE) and sexual desire score measured daily using an electronic diary (eDiary). Secondary endpoints included change from baseline to study end in female sexual function index (FSFI) desire domain and total scores, female sexual distress scale-revised (FSDS-R) Item 13 and total scores, and patient's global impression of improvement. Flibanserin 50 mg and 100 mg led to increases in SSE (P < 0.05 and P < 0.01 vs. placebo, respectively). There was a numerical trend toward improvement in eDiary desire score on flibanserin 100 mg, but statistical significance was not reached (P = 0.07 vs. placebo). FSFI desire domain and total scores increased with both flibanserin regimens (P < 0.05). FSDS-R total and Item 13 scores decreased with flibanserin 100 mg (P < 0.001), indicating reduced sexual distress. More women receiving flibanserin 50 mg and 100 mg considered their HSDD to have improved than women receiving placebo (39.6% and 50.0% vs. 30.3%, respectively) (P < 0.05). In premenopausal women with HSDD, flibanserin 50 mg and 100 mg once daily at bedtime were well tolerated and associated with statistically significant improvements in SSE, sexual desire (FSFI desire domain score but not eDiary desire score) and overall sexual function, and reduction of sexual distress, vs. placebo.

Treatment of Hypoactive Sexual Desire Disorder in Premenopausal Women: Efficacy of Flibanserin in the DAISY Study

Hypoactive Sexual Desire Disorder (HSDD) is characterized by low sexual desire that causes marked distress or interpersonal difficulty. To assess the efficacy and tolerability of flibanserin, a postsynaptic 5-HT1A agonist/5-HT2A antagonist, in the treatment of premenopausal women with HSDD. North American premenopausal women with HSDD (mean age 35 years) were randomized to 24 weeks' treatment with flibanserin 25 mg twice daily (N=396), 50 mg twice daily (N=392), 100 mg once daily at bedtime (N=395), or placebo (N=398). Co-primary endpoints were changed from baseline to study end in number of satisfying sexual events (SSE) and sexual desire score, measured daily using an eDiary. Secondary endpoints included change in Female Sexual Distress Scale-Revised (FSDS-R) total score and Item 13 score (distress due to low sexual desire), Female Sexual Function Index (FSFI) total and desire domain scores, and Patient's Global Impression of Improvement. Flibanserin 100 mg once daily was associated with an increase in SSE (P<0.01 vs. placebo) but the 25 mg and 50 mg twice daily doses were not. No group showed a significant increase in eDiary desire score vs. placebo. All flibanserin regimens improved FSDS-R total, FSDS-R Item 13, FSFI total, and FSFI desire domain scores vs. placebo (P<0.05, for all). More women receiving flibanserin 50 mg twice daily and 100 mg once daily considered their HSDD to have improved than women receiving placebo (44.1% and 47.0% vs. 30.3%, respectively) (P<0.000, 1 vs. placebo). The most frequently reported adverse events in women receiving flibanserin were somnolence (11.8%), dizziness (10.5%), and fatigue (10.3%). In premenopausal women with HSDD, flibanserin 100 mg once daily was well tolerated and associated with statistically significant improvements in SSE, sexual desire (FSFI desire domain score but not eDiary desire score), sexual function, and decrease in sexual distress vs. placebo.

Continued Efficacy and Safety of Flibanserin in Premenopausal Women with Hypoactive Sexual Desire Disorder (HSDD): Results from a Randomized Withdrawal Trial

Flibanserin is a 5-HT(1A) agonist/5-HT(2A) antagonist that has been shown to increase sexual desire and reduce distress in premenopausal women with Hypoactive Sexual Desire Disorder (HSDD). To assess the efficacy and safety of flibanserin over 24 weeks of double-blind treatment vs. placebo in premenopausal women with HSDD who showed a predefined response after 24 weeks of open-label treatment with flibanserin. Women (N = 738) were treated with open-label, flexible-dose flibanserin (50 mg or 100 mg/day) for 24 weeks. At week 24, women who showed a predefined response, measured using an eDiary, were randomized to 24 weeks of continued flibanserin therapy at optimized dosage (N = 163) or placebo (N = 170). The criteria for entering the double-blind phase were an increase from baseline to weeks 21-24 of ≥2 satisfying sexual events (SSE) and/or ≥4 "desire days." A "desire day" was one in which a woman reported more than "no" desire. Coprimary endpoints were change from randomization to study end in SSE and desire score. Secondary measures included change in Female Sexual Function Index (FSFI) total and desire domain scores and Female Sexual Distress Scale-Revised (FSDS-R) total and Item 13 scores. During the open-label period, mean SSE and desire score approximately doubled, and FSFI, FSDS-R total, and Item 13 scores improved. At the end of the double-blind period, flibanserin was superior to placebo in change from randomization in SSE, desire score, FSFI desire domain and total scores, and FSDS-R total and Item 13 scores (P < 0.05, for all). Flibanserin was well tolerated, and withdrawal reactions were not observed. At the end of the 24-week randomized withdrawal phase of a 48-week trial in premenopausal women with HSDD, flibanserin was superior to placebo on measures of SSE, sexual desire, overall sexual function, and sexual distress. Flibanserin was well tolerated, and no withdrawal reactions were observed following discontinuation.

A Randomized Trial of Oral DHEA Treatment for Sexual Function, Well-Being, and Menopausal Symptoms in Postmenopausal Women with Low Libido

IntroductionDehydroepiandrosterone (DHEA) and its sulfate DHEAS, which are the most abundant steroids in women, decline with age. We have shown association between low sexual function and low circulating DHEAS levels in women. AimThe aim of this study was to evaluate whether restoration of circulating DHEA levels in postmenopausal women to the levels seen in young individuals improves sexual function. MethodsNinety-three postmenopausal women not using concurrent estrogen therapy were enrolled in a 52-week randomized, double-blind, placebo controlled trial and received either DHEA 50 mg or placebo (PL) daily. Main Outcome MeasuresEfficacy was assessed through 26 weeks. The main outcome measures were the change in total satisfying sexual events (SSE) and the change in the Sabbatsberg Sexual Self-Rating Scale (SSS) total score. Secondary measures were the Psychological General Well-Being Questionnaire (PGWB), and the Menopause—Specific Quality of Life Questionnaire (MENQOL). Hormonal levels, adverse events (AEs), serious adverse events (SAEs) and clinical labs were evaluated over 52 weeks. ResultsEighty-five participants (91%) were included in the 26-week efficacy analysis. There were no significant differences between the DHEA and PL groups in the change in total SSE per month or the SSS, PGWB, and MENQOL change scores. Overall AE reports and number of withdrawals as a result of AEs were similar in both groups; however more women in the DHEA group experienced androgenic effects of acne and increased hair growth. ConclusionsIn this study treatment of postmenopausal women with low sexual desire with 50 mg/day DHEA resulted in no significant improvements in sexual function over PL therapy over 26 weeks. Panjari M, Bell RJ, Jane F, Wolfe R, Adams J, Morrow C, and Davis SR. A randomized trial of oral DHEA treatment for sexual function, well-being and menopausal symptoms in postmenopausal women with low libido. J Sex Med 2009;6:2579–2590.