Female Sexual Function Index Desire Domain 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.

Self-Perception of Sexual Dysfunction of Adult Brazilian Women of Reproductive Age: A Cross-Sectional Study.

Sexual dysfunction (SD) comprises disorders in sexual desire, arousal, orgasm, and lubrication. The importance of self-perceived SD relies on its relation to personal values, sex education, and partnership. We aimed to analyze the association between self-perceived SD and the Female Sexual Function Index (FSFI) in adult women of reproductive age and the correlation between age and sexual function. This analytical cross-sectional study included 285 women aged 18 to 49 years, sexually active for at least four weeks, cisgender and heterosexual, and with Internet access. Women were divided into control (CG, control group; without SD) or study group (SG, study group; with SD) and responded to a self-applicable online survey containing a sociodemographic characterization, an interview about SD knowledge, and the FSFI test. The Chi-square test of independence (χ2) analyzed the association between self-perceived SD and FSFI-assessed SD. Pearson's correlation coefficient investigated the correlation between age and FSFI. Included women had a mean age of 29.57 years ± 7.11 years. Self-perceived SD showed a moderate association (Cramer's V = 0.590) with the FSFI score (χ2 [2] = 91.500; p < 0.001). A weak, negative, and significant correlation was observed between age and the FSFI desire domain (r = -0.120; p = 0.030; r2 = 1.440). Women with self-perceived SD were 68% more likely to present FSFI-assessed SD. Regarding the FSFI desire domain, sexual function decreased with age.

(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

Female sexual function in women using LARC methods

Objective This study aims to assess sexual function (SF) and quality of life (QoL) among women using copper intrauterine devices (Cu-IUD), levonorgestrel-releasing intrauterine system (LNG-IUS) or etonogestrel(ENG)-releasing subdermal implant. Methods This is a cross-sectional study involving 213 women who are sexually active, using Cu-IUD, LNG-IUS or ENG implant for at least one year. SF assessment was carried out through the Female Sexual Function Index (FSFI) and QoL was made through The Short Form Health Research. Results Frequency of sexual dysfunction score in Cu-IUD users was 33.8%; 47.2% in LNG-IUS users and 47.8% in ENG-implant users, without difference between groups. Desire domain had higher score in Cu-IUD users (Cu-IUD:4.20 ± 1.15 × LNG-IUS:3.76 ± 1.17 × ENG-implant:3.63 ± 1.15; p = .009). Between Cu-IUD and LNG-IUS users there was no difference in FSFI score. Total FSFI score was higher in Cu-IUD group when compared only to ENG-implant (Cu-IUD:27.48 ± 6.14 × Implant:25.07 ± 6.89; p = .029). Regarding the QoL score, difference was found only in general health domain (Cu-IUD:65.22 ± 14.91 × LNG-IUS:62.61 ± 19.04 × Implant:58.33 ± 16.46; p = .034), with lower score for implant group. Conclusion There was no difference in the SF total score between the users of Cu-IUD, LNG-IUS and ENG implant. However, the score of the FSFI desire domain and general health status were higher among users of the Cu-IUD.

FDA Decisions on Measures of Hypoactive Sexual Desire Disorder in Women: A History, With Grounds to Consider Clinical Judgment.

In 2000, the FDA began issuing advice about treatments for hypoactive sexual desire disorder (HSDD) in women. How its recommendations have evolved has not been reviewed. Its consistent preference for self-rating by patients over evaluation by an examining clinician has not been addressed. Recount the changes in FDA's proposals about patient-reported outcomes and diagnostics. Compare the value of patient-reported measures and clinical interviews. Historical review is based on draft guidances, publications, meetings, and prescribing information. The FDA has avoided clinician input into diagnosis and evaluation of the severity of HSDD in women. It abandoned its initial (2000) insistence on counts of satisfying sexual events to define efficacy in favor of symptom-related scales to evaluate desire and distress with daily self-ratings. By 2015, the FDA accepted the self-rated Female Sexual Function Index-Desire Domain (FSFI-D) to measure desire and the most relevant item of the Female Sexual Distress Scale-Revised (FSDS-R) to measure distress; retrospection for both is one month. TheFDA rejected the one clinician-rated broad measure of HSDD, the Sexual Interest and Desire Inventory (SIDI-F), although well-validated and treatment-sensitive. Since 2005, the FDA has accepted the Decreased Sexual Desire Screener (DSDS) to diagnose HSDD by non-expert clinicians using self-ratings and exploring them in more depth in a clinical interview. FDA's decisions on how to measure HSDD in women may have stabilized on accepting 2 co-primary measures: the FSFI-D and the FSDS-R item on bother about low desire, and on accepting the DSDS for diagnosis. FDA's rejection of clinician ratings of severity through interviews in clinical trials seems unsound because interviews can give broader assessments than (brief) self-ratings, although the agency's logic was to avoid diagnostic controversies and help avoid overcommercialization. Semistructured clinical interviews for diagnosis (DSDS) and severity-rating (SIDI-F) are well validated and are recommended for clinical practice. Pyke RE. FDA Decisions on Measures of Hypoactive Sexual Desire Disorder in Women: A History, With Grounds to Consider Clinical Judgment. Sex Med Rev 2021;9:186-193.

Lifestyle modifications alone or combined with hormonal contraceptives improve sexual dysfunction in women with polycystic ovary syndrome

To describe the prevalence of female sexual dysfunction in a well-defined polycystic ovary syndrome (PCOS) population, and to assess the impact of common PCOS treatments on sexual function. Secondary analysis of a randomized controlled trial, oral contraceptive pills and weight loss in PCOS. Two academic medical centers. Women with PCOS (N = 114) defined by the Rotterdam criteria. Continuous oral contraceptive pill (OCP) or intensive lifestyle modification (Lifestyle) or the combination (Combined) for 16 weeks. Change in Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) scores after 16 weeks. There was no change in total FSFI or FSDS-R score in any treatment group; however, an increase in the FSFI desire domain subscore was observed in the Lifestyle and Combined treatments, indicating improved sexual desire over the 16-week period. Overall, 33 participants (28.9%) met criteria for sexual dysfunction by FSFI criteria (baseline score ≤26.55). Among this group, FSFI score improved after 16 weeks of Lifestyle and Combined treatments. There was no change in prevalence of sexual dysfunction in treatment groups at 16 weeks. Use of OCPs did not alter FSFI scores. Female sexual dysfunction is highly prevalent among women with PCOS. Our findings suggest that common treatments for PCOS, including intensive lifestyle modification and the combination of intensive lifestyle modification and OCPs, have the potential to improve sexual function in these women; the mechanism for these improvements is likely multifactorial. NCT00704912.

Instruments for Screening, Diagnosis, and Management of Patients with Generalized Acquired Hypoactive Sexual Desire Disorder.

Screening, diagnosis, and management of hypoactive sexual desire disorder (HSDD) and research into the condition have been challenging due to its biopsychosocial complexity and lack of consensus on relevant measures. Although physician interviews yield much clinically valid information, self-reported questionnaires appear more acceptable to patients and physicians. Consequently, validated patient-reported outcome (PRO) tools are essential for evaluation and management of HSDD, including any therapeutic intervention. The US Food and Drug Administration (FDA) has issued guidance on the use of appropriate endpoints and associated measures for female sexual dysfunction, including HSDD. Although many of the available measures were not designed specifically for HSDD assessment, as per FDA guidelines, most clinical studies have used individual domains or items from established tools, such as the Female Sexual Function Index-desire domain and Item 13 of the revised Female Sexual Distress Scale. For clinical practice, several professional societies recommend the Decreased Sexual Desire Screener and/or a sexual history as tools to diagnose HSDD. This review discusses frequently used PRO tools as well as the newly developed and validated Elements of Desire Questionnaire, which may be appropriate for clinical trials or clinical practice.

193 Bremelanotide for Hypoactive Sexual Desire Disorder: Contraceptive Subgroups Efficacy Analysis

Hypoactive sexual desire disorder (HSDD) is the most common sexual dysfunction associated with personal distress in women, and is characterized by an absence or deficiency of sexual desire accompanied by distress. HSDD affects approximately 10% of women, with a similar prevalence regardless of age. Bremelanotide, a melanocortin receptor agonist and an analog of the endogenous neuropeptide α-melanocortin stimulating hormone, has been approved for the treatment of acquired, generalized HSDD in premenopausal women. The RECONNECT studies, which comprised two double-blind, randomized, placebo-controlled studies, demonstrated that subcutaneous self-administration of bremelanotide significantly improved sexual desire and decreased personal distress in premenopausal women with HSDD. To investigate the efficacy of bremelanotide across hormonal contraceptive subgroups in the RECONNECT studies. Patients self-administered bremelanotide 1.75 mg or placebo subcutaneously for 24 weeks, using an autoinjector pen as needed prior to sexual activity. Patients were evaluated (“yes” and “no” subgroups) based on concurrent use of hormonal contraceptives (including oral contraceptives and other estrogen-containing products). Efficacy was assessed using RECONNECT co-primary endpoints: change from baseline to end-of-study (EOS) for Female Sexual Function Index–desire domain (FSFI-D) and Female Sexual Distress Scale–Desire/Arousal/Orgasm (FSDS-DAO) Item 13 scores.

Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder.

To evaluate the long-term safety and efficacy of bremelanotide as treatment for hypoactive sexual desire disorder in premenopausal women. Women who completed the 24-week double-blind core phase of RECONNECT, composed of two parallel phase 3 trials (301 and 302) examining the safety and efficacy of bremelanotide compared with placebo in premenopausal women with hypoactive sexual desire disorder, could enroll in the 52-week open-label extension, provided they had not experienced serious adverse events during the core phase. Efficacy was assessed using the coprimary endpoints from the core phase, and all adverse events were collected during the open-label extension. All statistical analyses were descriptive. The study 301 open-label extension began on July 17, 2015, and concluded on July 13, 2017; the study 302 open-label extension began on October 5, 2015, and concluded on June 29, 2017. Of the 856 eligible patients who completed the core phase, 684 elected to participate in the open-label extension, and 272 completed it. The most common treatment-emergent adverse events considered related to study drug were nausea (40.4%), flushing (20.6%), and headache (12.0%), and the only severe treatment-emergent adverse event experienced by more than one participant in both studies was nausea during the open-label extension. The change in Female Sexual Function Index-desire domain score and Female Sexual Distress Scale-Desire/Arousal/Orgasm item 13 from baseline to end of the open-label extension ranged from 1.25 to 1.30 and -1.4 to -1.7, respectively, for patients who received bremelanotide during the core phase, and 0.70-0.77 and -0.9, respectively, for patients who received placebo during the core phase. During the 52-week open-label extension of RECONNECT, no new safety signals were observed, and premenopausal women treated with bremelanotide exhibited sustained improvements in hypoactive sexual desire disorder symptoms. ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302). Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.

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

BackgroundResponder 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. AimTo 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). MethodsThe 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. OutcomesMCIDs 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. ResultsOutcomes 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 ImplicationsThese 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 & LimitationsMCIDs 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. ConclusionBremelanotide 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.

Efficacy of Bremelanotide Across Hypoactive Sexual Desire Disorder Duration Subgroups [15M

INTRODUCTION: Bremelanotide, an investigational new drug, demonstrated efficacy in premenopausal women with hypoactive sexual desire disorder (HSDD) in the RECONNECT studies. In this analysis, bremelanotide efficacy was investigated across HSDD duration subgroups. METHODS: RECONNECT comprised two replicate, phase 3, double-blind, randomized, placebo-controlled, IRB-approved studies. Subjects self-administered bremelanotide 1.75 mg or placebo using an autoinjector pen, on demand, for 24 weeks. Subjects were evaluated based on HSDD duration at baseline. Efficacy was assessed using RECONNECT co-primary endpoints: change from baseline to end-of-study (EOS) for Female Sexual Function Index-desire domain (FSFI-D) and Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) Item 13 scores. RESULTS: In the integrated population of RECONNECT (N=1202), differences in mean change in FSFI-D and FSDS-DAO Item 13 from baseline to EOS (bremelanotide-placebo) were 0.35 and -0.33, respectively (P<.0001 for both endpoints). Differences in mean FSFI-D changes from baseline to EOS for each duration quartile were 0.42 (6-18 months; N=174-177), 0.41 (>18-33 months; N=118-132), 0.28 (>33-60 months; N=158-167), and 0.33 (>60-360 months; N=131-144). Differences in mean FSDS-DAO Item 13 changes for each duration quartile were -0.46 (6-18 months), -0.43 (>18-33 months), -0.14 (>33-60 months), and -0.29 (>60-360 months). Significantly greater (P≤.0082) changes in FSFI-D were achieved with bremelanotide versus placebo in all HSDD duration quartiles. FSDS-DAO Item 13 was also significantly improved across duration quartiles (P≤.0295) except for the 33-60 months quartile (P=.2449). CONCLUSION: Bremelanotide demonstrated efficacy in premenopausal women regardless of HSDD duration. Bremelanotide significantly restored sexual desire across HSDD duration quartiles and showed improvements in decreasing distress.

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.

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%).

Aromatase Inhibitors Are Associated With Low Sexual Desire Causing Distress and Fecal Incontinence in Women: An Observational Study

BackgroundLittle is known of the impact of aromatase inhibitor (AI) therapy on sexual and pelvic floor function. AimTo document the prevalence of, and factors associated with, low desire, sexually related personal distress, hypoactive sexual desire dysfunction (HSDD), and pelvic floor dysfunction in women 10 years after breast cancer diagnosis. MethodsThis was a prospective, observational, community-based cohort study of Australian women with invasive breast cancer recruited within 12 months of diagnosis. 1,053 of the 1,305 who completed the initial 5 years of study follow-up agreed to be re-contacted, and 992 of these women alive 10 years after diagnosis were sent the study questionnaire. OutcomesThe main outcome measure was HSDD determined by a score no higher than 5.0 on the desire domain of the Female Sexual Function Index (FSFI) plus a score of at least 11.0 on the Female Sexual Distress Scale–Revised (FSDS-R). Pelvic floor disorders, including urinary incontinence, fecal incontinence, and pelvic organ prolapse, were assessed using validated questionnaires. Multivariable logistic regression was used to assess factors associated with low desire, personal distress, and HSDD. Results625 completed questionnaires were returned. The respondents’ median age was 65.1 years (range = 36.4–95.5). Current AI use was reported by 10% and tamoxifen use was reported by 3.4%. 521 of the 608 women (85.7%; 95% CI = 82.9–88.5) who competed the FSFI desire domain had low sexual desire, and 246 of the 563 women (43.7%; 95% CI = 39.6–47.8%) who completed the FSDS-R had sexually related personal distress. 221 of the 559 women (39.5%; 95% CI = 35.5–43.6%) who completed the 2 questionnaires had HSDD. Current AI users were more likely to have HSDD than non-users (55.2% [95% CI = 42.2–68.1] vs 37.8% [95% CI = 33.5–42.0]; P = .01). HSDD was more prevalent in sexually active, current AI users (66.7%; 95% CI = 49.4–83.9) vs current non-users (43.6%; 95% CI = 37.0–50.2; P = .02). In a logistic regression model, HSDD was significantly associated with current AI use and inversely associated with age. Fecal incontinence was more prevalent in AI users than in current non-users (29.8% [95% CI = 17.8–41.8] vs 16.4% [95% CI = 13.2–19.6], respectively; P = .01). Clinical ImplicationsIt is important to address women’s sexual health even many years after their breast cancer diagnosis. Strengths and LimitationsStrengths include a representative sample, use of validated questionnaires, and few missing data. Limitations include sexual activity being a 4-week recall. ConclusionsAI use is associated with HSDD and fecal incontinence in women who are 10 years after breast cancer diagnosis.Robinson PJ, Bell RJ, Christakis MK, et al. Aromatase Inhibitors Are Associated With Low Sexual Desire Causing Distress and Fecal Incontinence in Women: An Observational Study. J Sex Med 2017;14:1566–1574.

Flibanserin in Postmenopausal Women With Hypoactive Sexual Desire Disorder: Results of the PLUMERIA Study

BackgroundHypoactive sexual desire disorder (HSDD) is a common sexual disorder in younger and older women. Flibanserin is approved for the treatment of acquired generalized HSDD in premenopausal women only. The efficacy of flibanserin for postmenopausal women with HSDD was demonstrated in the first of two North American randomized, double-blinded, placebo-controlled trials (SNOWDROP). AimTo evaluate the safety and efficacy of flibanserin in postmenopausal women with HSDD in a second randomized, double-blinded, placebo-controlled trial (PLUMERIA). MethodsNaturally postmenopausal women were randomly assigned to receive flibanserin (100 mg/d) or placebo. Efficacy outcomes were assessed using the last-observation-carried-forward imputation method. OutcomesSafety assessment included incidence of adverse events. Primary efficacy outcomes were the number of satisfying sexual events and the Female Sexual Function Index desire domain (FSFI-d) score. ResultsThe study population (flibanserin, n = 376; placebo, n = 369) included primarily white women (84.7%), with a mean age of 56.1 years and a mean HSDD duration of 5.0 years. When the study was discontinued early by the sponsor, 45.3% of randomly assigned patients had completed week 16 (which served as the primary analysis time point). The most common adverse events in flibanserin-treated patients were insomnia (7.7%), somnolence (6.9%), and dizziness (6.4%). Improvement from baseline to week 16 (last-observation-carried-forward) in FSFI-d score was significantly greater for flibanserin compared with placebo (P = .011); however, the between-group comparison for satisfying sexual events did not reach statistical significance. Clinical ImplicationsConsidered with the findings of the previous randomized controlled trial (SNOWDROP), the results of this study support the safety and efficacy of flibanserin in postmenopausal women. Strengths and LimitationsThis was a well-designed randomized, placebo-controlled trial. A key limitation was early discontinuation by the study sponsor, which decreased the sample size. In addition, the validity of satisfying sexual events as a primary outcome measurement in HSDD studies has been called into question (but was required by the US Food and Drug Administration as a primary end point in studies of female sexual dysfunction at the time this study was conducted). ConclusionFlibanserin was generally well tolerated in this population of naturally postmenopausal women. Despite the greatly decreased power to detect improvement compared with placebo on the efficacy measurements used, results suggest that flibanserin could be efficacious in postmenopausal women with HSDD.Portman DJ, Brown L, Yuan J, et al. Flibanserin in Postmenopausal Women With Hypoactive Sexual Desire Disorder: Results of the PLUMERIA Study. J Sex Med 2017;14:834–842.

Effect of Flibanserin on Sexual Functioning: An Analysis of Female Sexual Function Index Domains [24H

INTRODUCTION: 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. The Female Sexual Function Index (FSFI) is a validated self-report questionnaire comprising 6 domains of sexual functioning: desire, arousal, lubrication, orgasm, satisfaction, and pain. This post hoc analysis evaluated the effect of flibanserin treatment across the 6 FSFI domains. METHODS: Patient-level data were pooled from three 24-week, double-blind, placebo-controlled studies of flibanserin 100 mg once daily (qhs) in premenopausal women with HSDD. Between group differences in change from baseline to week 24 (last observation carried forward [LOCF]) on FSFI domain and total scores were evaluated using analysis of covariance. RESULTS: This analysis included 2368 women (flibanserin, n=1165; placebo, n=1204) who had at least one on-treatment efficacy assessment. The least-squares mean differences (standard error of the mean) in change scores from baseline to week 24 (LOCF) for flibanserin versus placebo were 0.3 (0.1) for the FSFI desire domain, 0.4 (0.1) for the arousal domain, 0.3 (0.1) for the lubrication domain, 0.3 (0.1) for the orgasm domain, 0.3 (0.1) for the satisfaction domain, 0.2 (0.1) for the pain domain, and 1.9 (0.3) for the total score; all P less than 0.0001 except P less than 0.01 for pain. CONCLUSION: Treatment with flibanserin produced significant improvement not only in the FSFI desire domain (a key outcome in clinical trials of HSDD) but also across the other domains of sexual function assessed by the FSFI.

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.

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.