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Introduction: Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause., Objective: The aim of this review is to provide a summary of the currently available evidence on the use of testosterone in the treatment of FSIAD in postmenopausal women., Methods: A narrative review on the topic was performed. Only randomized controlled trials (RCTs) and systematic reviews and meta-analysis were considered. 123 articles were screened, 105 of them assessed for eligibility, and finally 9 were included in qualitative synthesis following the PRISMA declaration., Results: Current evidence recommends, with moderate therapeutic benefit, the use of systemic transdermal testosterone within the premenopausal physiological range in postmenopausal women with Hypoactive Sexual Desire Disorder (HSDD), the previous entity for low desire dysfunction, not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. The available evidence is based on studies with heterogeneity on their design (different testosterone doses, routes of administration, testosterone use in combination and alone, sexual instruments of measurement). There is no data indicating severe short-term adverse effects, although long-term safety data is lacking., Conclusions: Despite having testosterone as a valuable tool, therapeutic strategies are lacking in the pharmacological field of HSDD/FSIAD. Neuroimaging studies could provide valuable information regarding the sexual desire substrate and suggest the potential application of already approved drugs for women with a good safety profile. The use of validated instruments for HSDD in postmenopausal women, considering the level of distress, is necessary to be able to draw robust conclusions on the evaluated treatments.

Background: Hypoactive Sexual Desire Disorder (HSDD) is a frequent sex-related problem in women; however, a specific tool to characterize HSDD subtypes based on sexual inhibitory and excitatory factors is still lacking., Aim: (1) To find a cutoff value in Sexual Inhibition Scale (SIS)/Sexual Excitation Scale (SES) scores predicting a diagnosis of HSDD in women consulting for sexual symptoms, (2) to explore the sexual inhibitory and excitatory profiles in women referred to a clinic for female sexual dysfunction by stratifying the sample according to the newfound cutoffs, and (3) to identify biopsychosocial factors significantly associated with the 2 profiles., Methods: An overall 133 women consulting for sexual symptoms were retrospectively evaluated for clinical, biochemical, and psychosexologic data collected at the first visit. A subgroup of 55 women treated with transdermal testosterone was retrospectively analyzed at baseline and the 6-month visit., Outcomes: Patients underwent physical and laboratory examinations and completed the SIS/SES, Female Sexual Function Index, Female Sexual Distress Scale-Revised, Emotional Eating Scale, and Middlesex Hospital Questionnaire., Results: Specific cutoffs for SIS1 (≥32.5; indicating threat of performance failure) and SES (≤46.5) predicted HSDD diagnosis with an accuracy of 66.4% (P = .002) and 68.7% (P < .0001), respectively. Patients with impaired SIS1 scores showed higher distress and psychopathologic symptoms, while those with impaired SES scores demonstrated lower desire and arousal and a negative association with some metabolic and hormonal parameters. SES score also showed a significant predictive value on testosterone treatment efficacy for HSDD., Clinical Translation: A better characterization of HSDD would enable individualized treatment based on the main underlying etiologies., Strengths and Limitations: Limitations of the study include the small sample size and cross-sectional retrospective design, with the choice of treatment for HSDD limited to transdermal testosterone. Strengths comprise the thorough and multifactorial evaluation of every aspect potentially affecting inhibitory and excitatory components of sexual desire., Conclusion: Validated cutoffs of SIS/SES scores could allow deep characterization of women diagnosed with HSDD, thus ensuring better tailoring of therapy and prediction of the probability of response to specific treatments., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This article contains noninclusive language such as "females" and "women" when those terms were used in the research and historic context we are summarizing. New therapies have become available for vasomotor symptoms, postpartum depression, contraception, osteoporosis, recurrent yeast infections, acute and recurrent urinary tract infections, and female hypoactive sexual desire disorder. These therapies meet unique patient needs and change clinical practice for select groups. As is typical for new treatments, insurance coverage and access issues limit the adoption of some therapies., Competing Interests: Disclosure Dr S. Merriam writes content for ACP MKSAP and is compensated., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Treating and changing patterns of low sexual desire and dysfunctions can be done in various ways. However, it is important to recognize the value of integrated approaches when it comes to addressing these issues. To this end, we conducted a randomized clinical trial study to compare the effectiveness of an integrated approach with that of Masters-Johnson Sex Therapy (MJST) for treating hypoactive sexual desire disorder (HSDD) in Iranian couples from Mar 2016 to May 2018., Methods: We conducted a clinical trial on 24 couples who were experiencing HSDD. The couples were randomly divided into two groups. The intervention group was given an integrative approach, while the control group received MJST for ten sessions. We collected data using standard questionnaires before, immediately after, and eight weeks after the intervention., Results: There was no significant difference in sexual desire and function among men between the MJST and integrative approach groups. However, women in the integrative approach group showed more improvement in sexual desire and dysfunction compared to those in the MJST group. The improvement in sexual function for women and sexual desire for both men and women were maintained at the eight-week follow-up in the integrative approach., Conclusion: Our study found that using an integrative approach effectively treated HSDD in couples., (Copyright© 2024 Samadi et al. Published by Tehran University of Medical Sciences.)

Female sexual dysfunction is highly prevalent, affecting 30% to 50% of cisgender women globally. Low sexual desire, sexual arousal disorder, and orgasm disorder affect 10% to 20%, 6% to 20%, and 4% to 14% of women, respectively. Dyspareunia or pain with intercourse affects 8% to 22% of women. Universal screening is recommended; and a thorough medical history and physical examination are the foundations of evaluation and assessment. Laboratory tests and imaging are sometimes warranted, but referral to a sexual medicine expert is suggested if the practitioner is unfamiliar or uncomfortable with treatment., Competing Interests: Disclosure S.J. Parish serves as a consultant for Dare Bioscience and received no funding for this article. R. Pope serves as a speaker for Astellas, a consultant for Johnson and Johnson Global Public Health, Materna MD, Mim, and Stardust, and received no funding for this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This review aims to provide an overview of pharmacologic management for hypoactive sexual desire disorder (HSDD) in premenopausal women, with a focus on available agents., Data Sources: Through a literature search on PubMed, Google Scholar, and ClinicalTrials.gov from 1999 to 2024, studies were selected using the following MeSH search terms: hypoactive sexual desire disorder, premenopause, pharmacologic management, flibanserin, bremelanotide, buspirone, bupropion, and testosterone, excluding those involving postmenopausal women or other sexual disorders. Product monographs were also reviewed., Study Selection and Data Extraction: Relevant English-language studies or those conducted in humans were considered., Data Synthesis: Hypoactive sexual desire disorder, characterized by a lack of motivation for sexual activity, predominantly affects women aged 45 years and older. Treatment involves a multimodal approach, including nonpharmacologic interventions such as psychotherapy and lifestyle adjustments, alongside pharmacologic options. Although bupropion and buspirone may be considered off-label treatments, flibanserin and bremelanotide are the sole medications approved by the Food and Drug Administration for generalized acquired HSDD in premenopausal women. However, caution is advised due to their limited efficacy, potential adverse effects, and transparency issues in reporting., Relevance to Patient Care and Clinical Practice: Hypoactive sexual desire disorder, while not life-threatening, significantly impacts well-being and relationships. Pharmacotherapy, including options like flibanserin and bremelanotide, is essential within a multidisciplinary approach. Validated tools and objective measures inform tailored premenopausal HSDD care plans and aid in striking a balance between potential risks and adverse effects while maximizing meaningful clinical benefits, including for transgender individuals., Conclusions: Clinicians must discern important distinctions between flibanserin, bremelanotide, and other agents when managing premenopausal HSDD. Further research with the most suitable clinical endpoints and consideration of patient factors are crucial before widespread adoption of flibanserin and bremelanotide. Pharmacists are encouraged to embrace this opportunity to provide premenopausal HSDD care in ambulatory and community practice settings., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hypoactive sexual desire disorder (HSDD) in men, characterized by chronically low sexual desire, is associated with poor sexual well-being, such as lower sexual satisfaction and higher sexual distress. Additionally, despite their low desire, men with HSDD often report wanting sexual intimacy and validation within their sexual lives/relationships. Studies that apply self-determination theory to sexual relationships demonstrate that adopting more autonomous (e.g., engaging in sex for its inherent pleasure) and less controlled (e.g., engaging in sex for some external reward or consequence) motives for engaging in sex is associated with greater sexual well-being for both members of the couple. Given that autonomous motivation in relationships is associated with intimacy and sexual satisfaction, and lower sexual distress, having sex for autonomous reasons may allow men with HSDD and their partners to feel more sexually intimate despite their lower sexual desire, whereas having sex for controlled reasons may hinder sexual intimacy and satisfaction and augment sexual distress. In this dyadic cross-sectional study, we examined the associations between types of sexual motivation and sexual intimacy, sexual satisfaction, and sexual distress for men with HSDD and their partners (n = 64 couples). Men with HSDD who reported having sex for more autonomous reasons reported more sexual satisfaction and both partners reported more sexual intimacy. Men with HSDD who had sex for more controlled reasons had partners who felt less sexual intimacy and satisfaction, and both partners were more sexually distressed. Promoting autonomous sexual motivation and decreasing controlled motivation may help couples navigating HSDD to feel closer in their relationship, more sexually satisfied, and less sexually distressed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Female sexual interest/arousal disorder (FSIAD) is the most common female sexual disorder with adverse effects on women's health and interpersonal relationships., Aim: This survey evaluated the effects of sexual counseling based on the "good enough sex" (GES) model on the sexual health variables of women with FSIAD., Methods: A randomized clinical trial with a 1:1 allocation ratio was conducted among 80 women with FSIAD in Iran in 2021. Eligible participants were randomly assigned to group A (women) and group B (couples). Women attended 4 weekly online group sexual counseling sessions based on the GES model, each lasting 120 minutes. In group B, husbands participated in sessions 2 and 3., Outcomes: Women's sexual health parameters-including sexual desire, sexual satisfaction, sexual function, sexual distress, sexual communication, frequency of sexual intercourse, and dysfunctional beliefs-were evaluated before and 3 months after counseling. The significance threshold considered P < .007 due to Bonferroni correction., Results: After the intervention, all sexual parameters except sexual dysfunctional beliefs showed significant improvement (P < .001) in both groups. During the follow-up period, the average scores for all sexual variables were slightly higher in group B vs group A. The between-group difference was significant only for frequency of sexual intercourse (P < .01)., Clinical Implications: This study reaffirms the impact of the GES model as biopsychosocial therapy in managing female sexual problems. Considering men's reluctance to accompany their wives to sex clinics, counseling for women alone can play a significant role in solving sexual problems, especially in the case of FSIAD. Online sexual consultation offers cost and time savings, provides a secure space for discussing sensitive topics, and facilitates group program coordination. It ensures universal access to counseling, thereby addressing gender incompatibility issues. It is a powerful, interactive, and acceptable alternative to in-person visits, providing convenience and confidentiality for clients seeking sexual health support., Strengths and Limitations: The following were among the survey strengths: conducting a randomized controlled trial on women with FSIAD by applying an appropriate model and scales, involving spouses, and evaluating online group sexual counseling. However, the results of this study may not be generalizable to women without partners., Conclusion: The GES model, emphasizing intimacy and sexual dialogue, reduces unrealistic sexual expectations and improves women's sexual desire and overall health. Our results showed that instead of insisting on the physical presence of husbands in counseling sessions, clinicians should emphasize their emotional support and companionship during the treatment process., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Women may experience changes in sexuality across menopause, because at this step in life hormone deficiency interacts with several determinants in a bio-psycho-social perspective. Healthcare providers should inform women about menopause impact on sexuality and be proactive during consultation in disclosing sexual concerns that would require a targeted assessment. Sexual symptoms become more frequent as women age, but they do not always translate into sexual dysfunction diagnosis, for which distress is required. It is important to recognize conditions that may increase the risk of dysfunctional response to menopause challenges in order to promote sexual longevity through counselling and specific management. In this review, we report key elements for a comprehensive assessment of sexual health around menopause, with a focus on genitourinary syndrome of menopause (GSM) and hypoactive sexual desire disorder (HSDD), representing well identified clinical conditions affecting sexuality at midlife and beyond. We also address the issue of contraception across the menopausal transition, highlighting risks and benefits, and possible implications on sexual function., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hypoactive sexual desire disorder (HSDD) in premenopausal women involves biological, psychological, and social aspects. In the European Society for Sexual Medicine meeting in Rotterdam in February 2023, several leading experts in the field discussed the multifaceted nature of this disorder and the state of the art regarding treatment at a round table. This review reflects the information discussed at this event and further discusses current controversies., Summary: HSDD is the most prevalent female-estimated sexual disorder reported by 28% of the 40% premenopausal women with sexual dysfunction. Flibanserin and bremelanotide are the only approved medications to treat HSDD in the USA, and none are approved in Europe. Lybrido, Lybridos, and Lorexys are under development. There are several psychological factors with impact in sexual desire, including depression and sexual abuse. Feminine sexual scripts, the pleasure gap, and structural inequalities also affect sexual desire. Evidence strongly supports the value of combining medical and psychological approaches in the treatment of HSDD, but there is ongoing controversy regarding the pharmacological treatment of young women with HSDD. However, some women seem open and would like to have access to drug treatment., Key Messages: The treatment of HSDD in young women requires a mixed treatment approach that addresses the disorder's complexity. Despite clinicians seeming to be divided between using pharmacological and/or psychosocial approaches, some women might respond better to one type of intervention over the others. This calls for the development of tools that assess the best approach for each person, including their will and informed choice., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Hypoactive Sexual Desire Disorder (HSDD) is a complex and multifaceted condition that significantly impacts the sexual well-being and overall quality of life of women. This comprehensive review aims to provide a holistic understanding of HSDD by exploring its etiology, diagnostic criteria, treatment approaches, and broader societal implications. The review delves into the intricate interplay of biological factors, including hormonal changes and neurotransmitter imbalances, that contribute to HSDD. Psychological factors, such as relationship issues, body image, and stress, are examined with sociocultural factors like societal norms, cultural influences, and media portrayals of sexuality. Diagnostic criteria and assessment methods, including The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, and self-report questionnaires, are explored to facilitate accurate identification of HSDD and differentiation from other sexual disorders. The impact of HSDD on women's quality of life and relationships is examined, highlighting the emotional strain and interpersonal challenges associated with the disorder. Societal and personal consequences of untreated HSDD underscore the need for increased awareness and support. Treatment approaches encompass non-pharmacological interventions such as cognitive-behavioral therapy, sex therapy, and couples therapy and pharmacological interventions like hormone therapy and selective serotonin reuptake inhibitors. Novel treatments like bremelanotide, flibanserin, and integrative strategies combining psychotherapy and lifestyle changes are discussed. Challenges and controversies surrounding HSDD, including the lack of consensus on diagnostic criteria, debates about the medicalization of sexuality, ethical concerns regarding pharmaceutical interventions, and cultural considerations, are addressed. Future directions in research, including advances in neurobiological understanding, personalized medicine, long-term treatment studies, and destigmatization initiatives, offer promising pathways for enhancing the management of HSDD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ronghe et al.)

Numerous surveys have documented that sexuality and/or sexual activity is important to women at all stages of adulthood, including postmenopause. Genitourinary syndrome of menopause (GSM) and hypoactive sexual desire disorder (HSDD) are common disorders in postmenopausal women and may co-occur. Both are often undiagnosed due to a lack of knowledge of the disorder, health-care professional discomfort in discussing sexual problems or a lack of routine screening. It is incumbent upon health-care professionals to identify and differentiate these conditions in women through a biopsychosocial assessment, and may require a focused physical examination. Numerous treatments, both non-pharmacologic and pharmacologic, are available to address GSM and HSDD.

Background: Hypoactive sexual desire disorder (HSDD) is characterized by persistently low desire and associated distress. Low desire is one of the most common sexual complaints among men and is associated with poor well-being. Interpersonal factors are key to understanding low desire, yet there are few dyadic studies of HSDD in men. Previous work on genito-pelvic pain and low desire in women has established that greater facilitative (eg, affectionate) partner responses are associated with greater sexual satisfaction and function and that more negative (eg, critical) or solicitous (eg, sympathetic, avoidant) partner responses are associated with lower sexual satisfaction and function. Examining how partner responses are associated with adjustment to HSDD may shed light on the interpersonal dynamics of this understudied sexual dysfunction., Aim: In a cross-sectional study, we examined whether partner responses to low desire in men were associated with sexual desire, sexual satisfaction, and sexual distress for both members of the couple., Methods: Men with HSDD and their partners (N  =  67 couples) completed measures of facilitative, negative, and avoidant partner responses to men's low sexual desire-as perceived by the man with HSDD and self-reported by their partner-and sexual desire, sexual satisfaction, and sexual distress. Data were analyzed using multilevel modeling guided by the actor-partner interdependence model., Outcomes: Outcomes included the partner-focused subscale of the Sexual Desire Inventory-2, Global Measure of Sexual Satisfaction, and Sexual Distress Scale-Revised., Results: When men with HSDD perceived more facilitative partner responses to their low desire, they and their partners reported greater sexual satisfaction. When men with HSDD perceived and their partners self-reported more negative partner responses, they each reported lower sexual satisfaction. In addition, when men with HSDD perceived more avoidant partner responses, their partners reported greater sexual distress. Partner responses were not associated with sexual desire for either member of the couple., Clinical Implications: Findings support the importance of the interpersonal context for HSDD in men and suggest potential future targets of treatment when working with affected couples., Strengths and Limitations: This study is one of the only dyadic studies of HSDD in men, as assessed via clinical interview or self-report symptoms reviewed by the clinical team. Despite our best efforts to recruit this sample over 6 years, the small size limited power to detect all predicted effects., Conclusion: More facilitative and fewer negative or avoidant partner responses to low desire are associated with greater sexual well-being in couples coping with HSDD., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.)

Background: The target population for women's sexual health services in China was unclear. To identify high-risk individuals with psychological barriers to sexual health-seeking behaviors and those at high risk of hypoactive sexual desire disorder (HSDD), we investigated correlates of Chinese women's unwillingness to communicate sexual health, the shame of sexual health-related disorders, sexual distress, and HSDD., Methods: An online survey was conducted from April to July 2020., Results: We received 3443 valid responses online (effective rate 82.6%). Participants were mainly Chinese urban women of childbearing age (median 26 years old, Q1-Q3 23-30). Women who knew little about sexual health knowledge (aOR 0.42, 95%CI 0.28-0.63) and were ashamed (aOR 0.32-0.57) of sexual health-related disorders were less willing to communicate sexual health. Age (aOR 4.29, 95%CI 2.26-8.17), low income (aOR 1.52-2.11), family burden (aOR 1.34-1.43), and living with friends (aOR 1.39, 95%CI 1.02-1.91) were independent correlates of women's shame about sexual health-related disorders while living with a spouse (aOR 0.66, 95%CI 0.51-0.86) or children (aOR 0.77, 95%CI 0.62-0.96) were correlated with less shame. Age (aOR 0.98, 95%CI 0.96-0.99) and a postgraduate degree (aOR 0.45, 95%CI 0.28-0.71) were linked with less sexual distress of low sexual desire while having children (aOR 1.38-2.10), intense work pressure (aOR 1.32, 95%CI 1.10-1.60) and heavy family burden (aOR 1.43, 95%CI 1.07-1.92) increased women's odds of having distress. Women with a postgraduate degree (aOR 0.42, 95%CI 0.19-0.90), more knowledge about sexual health (aOR 0.53-0.67), and decreased sexual desire caused by pregnancy, recent childbirth, or menopausal symptoms (aOR 0.60, 95%CI 0.41-0.85) were less likely to have HSDD, while they were more likely to have HSDD when their decreased sexual desire was due to other sexual issues (aOR 2.56, 95%CI 1.84-3.57) and partners' sexual problems (aOR 1.72, 95%CI 1.23-2.39)., Conclusion: Sexual health education and related services need to focus on psychological barriers of women with older age, insufficient knowledge of sexual health, intense work pressure, and poor economic conditions. The medical staff need to pay attention to the sexual health of women with intense work or life pressure and a history of gynecological disease. Low sexual desire is not equal to the sexual desire problem, which should be noticed in the future., (© 2023. The Author(s).)

Background: Sexuality has a key impact on quality of life and on reproductive health. Infertility often results in sexual dysfunction. Despite this close association, addressing sexuality is not a standard component of infertility counselling, especially since in most countries sexual medicine is not a core element of specialist training. Even today, many doctors and patients consider discussing sexuality to be more challenging than other aspects of reproductive medicine. The present review addresses the complex consequences of infertility on sexuality., Objective and Rationale: Our goals were: (i) to identify the prevalence of sexual problems resulting from infertility, (ii) to evaluate characteristics of sexual difficulties and disorders resulting from infertility and (iii) to analyse factors involved in the complex association between sexual problems and infertility., Search Methods: A systematic search for publications containing keywords related to sexual disorders and infertility was performed via PubMed, Web of Science and Psyndex. A total of 170 manuscripts published between January 1966 and April 2021 were identified after verification of inclusion and exclusion criteria. The reference lists in these manuscripts were searched for further relevant literature. Studies were reviewed for quality-related methodological details., Outcomes: Couples diagnosed with infertility have an increased risk of sexual disorders. Loss of sexual desire and erectile dysfunction are among the most frequent sexual disorders resulting from infertility. Currently available literature reflects only fragmentarily the complexity of the diverse interactions. Sexuality plays out against the backdrop of interactions among personal, cultural, infertility-related and sexuality-related factors. Considering this complexity, it is crucial to evaluate individual profiles as well as partnership interactions to avoid a negative impact of infertility on a couple's sexual life., Wider Implications: Identifying sexual disorders as relevant considerations in the context of infertility and exploring their impact during the entire course of diagnosis and treatment constitute an important contribution to comprehensively care for the couples concerned. Counselling should focus on preventing the onset and aggravation of sexual disorders. As sexuality represents a major component of quality of life and of partnership, such support may improve not only the current overall wellbeing but also the chances of a satisfactory long-term partnership and family life., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Female sexual response implies a deep intertwining between psychosocial and neurobiological mediators. Regulation of central melanocortin signaling may enhance sexual desire. In premenopausal women with hypoactive sexual desire disorder (HSDD), melanocortin receptor agonist bremelanotide (Vyleesi) has been hypothesized to trigger excitatory brain pathways., Areas Covered: Hereby we summarize bremelanotide's proposed mechanism of action, pharmacokinetics, efficacy and safety data derived from clinical trials. A literature search of peer-reviewed publications on the current evidence on the pharmacotherapy with bremelanotide was performed using the PubMed database., Expert Opinion: Bremelanotide appears to be moderately safe and well-tolerated; the most common adverse reaction is nausea (40%). Although data from clinical trials demonstrated a significant change in validated questionnaires, the overall clinical benefit appears to be modest. However, these results should be interpreted in the light of the dramatic challenges in conducting well-designed clinical trials for female sexual dysfunction, due to the significant placebo effect of pharmacotherapy, and the frequent use of outcome measures that are likely to be highly susceptible to expectation biases, such as long periods of recall of sexual and emotional response.

Introduction: Flibanserin treatment increases sexual desire and satisfying sexual events while decreasing distress in certain women diagnosed with acquired, generalized hypoactive sexual desire disorder (HSDD). Additional aspects of sexual function and the time course of response have not been fully characterized., Aim: To evaluate changes in sexual function assessed by the subdomains of the Female Sexual Function Index (FSFI) in women with HSDD treated with flibanserin., Methods: FSFI data pooled from 3 pivotal flibanserin trials in premenopausal women (flibanserin = 1,165; placebo = 1,203) and FSFI data from one complete flibanserin trial in postmenopausal women (flibanserin = 432; placebo = 463) were subjected to post-hoc analyses. For each FSFI subdomain, least squares mean change from baseline was calculated at each assessment visit (treatment weeks 4, 8, 16, 24) and treatment groups were compared using analysis of covariance. Standardized effect size (Cohen's d) was also determined for each FSFI subdomain., Main Outcome Measure: Changes from baseline in FSFI subdomains., Results: Compared to placebo, both premenopausal (P < .02) and postmenopausal (P < .045) patients in the flibanserin group reported significantly greater increases over baseline in the FSFI subdomain scores of desire, arousal, lubrication, orgasm, and satisfaction. In premenopausal patients, significant improvements were observed at the first assessment of response (week 4) and were maintained through week 24. In postmenopausal patients, significant improvements were observed at week 4 for desire and arousal, while significant improvements in lubrication, orgasm, and satisfaction were observed at week 8. At week 24, excluding the pain subdomain, standardized effect sizes ranged from 0.18 to 0.28 in the premenopausal cohort and 0.12 to 0.29 in the postmenopausal cohort. In both pre- and postmenopausal patients, improvements in pain were smaller and largely undifferentiated between treatment groups., Clinical Implications: While variations in time to response should be taken into consideration, on average, the beneficial impact of flibanserin on overall sexual function occurs within the first month of treatment. The data also suggest that the response to flibanserin is sustained for the duration of treatment., Strengths and Limitations: Sexual function assessments were performed in a large cohort of 2,368 premenopausal women and 895 postmenopausal women. However, the FSFI assesses changes over a 1-month period and time points earlier than 4 weeks could not be assessed., Conclusion: These analyses suggest that assessment of benefit of flibanserin in HSDD should include improvements across all domains of sexual function, not only desire. Simon JA, Clayton AH, Goldstein I, et al. Effects of Flibanserin on Subdomain Scores of the Female Sexual Function Index in Women With Hypoactive Sexual Desire Disorder. Sex Med 2022;10:100570., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Female sexual dysfunction is a prevalent condition affecting 12% of women, yet few academic centers in the US have female sexual medicine programs., Aim: To characterize female sexual health programs in the United States, services offered, and training of female sexual health providers., Methods: We performed an internet search to identify female sexual health programs and clinics in the US. From each programs' website we abstracted the location, clinic setting (academic vs private), training of providers, and whether the clinic provided investigational services (ie, PRP injections, laser/radiofrequency therapy). We categorized clinics as specialized in sexual medicine, specialized with a focus on cancer patients, general, aesthetics-focused, general & aesthetic, or specialized & aesthetic. We used Chi-square and Fisher's exact test to evaluate association between practice setting and provision of investigational therapies with a Bonferroni-adjusted critical P-value of 0.017., Outcomes: Our outcomes were the number of clinics in each setting, in each category, and each state, as well as the number of providers by training type., Results: We identified 235 female sexual medicine programs in the United States. Seventeen percent were in the academic setting. Clinics in the non-academic setting were significantly (α = 0.017) more likely to offer PRP injections (0% vs 47%, P < .001), laser/radiofrequency therapy (14% vs 56%, P < .0001), and shockwave therapy (0% vs 14%, P = .011). Among all clinics, 22% provided specialized care, 2% provided care for cancer patients, 29% were more general clinics that advertised female sexual healthcare, 23% were aesthetics-focused, 22% were general practices that provided aesthetics services, and 2% were specialized clinics that offered aesthetics services. 81% of aesthetics-focused clinics advertised PRP injections. Seven states had no clinics and 26 states lacked a clinic specializing in female sexual health. The most frequent providers were OB/Gyns (40%), nurse practitioners (22%), urologists (13%), and physicians assistants (10%)., Clinical Implications: The geographic distribution of clinics and pervasiveness of clinics offering investigational services for female sexual dysfunction may be a barrier for patients seeking care., Limitations: As a result of our internet search methodology, we likely did not capture all clinics providing female sexual health services. Further, the accuracy of our data depends on the level of detail provided on each clinics' website., Conclusion: Online search identified few clinics providing female sexual healthcare in academic medicine: development of such clinics could benefit patients by improving access to evidence-based care and promoting training of future providers. Elizabeth E. Stanley and Rachel J. Pope, Characteristics of Female Sexual Health Programs and Providers in the United States. Sex Med 2022;10:100524., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Hypoactive Sexual Desire Disorder (HSDD) is a very prevalent sexual problem, with limited options for treatment. Given that psychological factors are major contributors to the disorder, a therapy such as Cognitive-Behavioral Therapy (CBT) may be useful to treat HSDD., Objective: To evaluate the effects of group CBT on women with HSDD., Method: Clinical trial randomized study with 106 women diagnosed with HSDD, who were divided as follows: Group 1 (n = 53) underwent group CBT for 8-weeks, and Group 2 (n = 53), were put on a waiting list and used as a control group. Sexual function was assessed by the Female Sexual Quotient (FSQQ) at the initial interview and after 6-months. Mann Whitney test was used for group comparison., Main Outcome Measures: demographics, education, sexual history, FSQQ and its domains for sexual function assessment., Results: Both groups had similar characteristics regarding sexual response, self-image, and relationship with a partner at the initial interview. Women undergoing therapy showed significant improvement in sexual function when compared with the control group. The overall FSQQ result showed an average growth of 18.08 points (95% CI 12.87‒23.28) for the therapy group against a decrease of 0.83 points (95% CI 3.43‒1.77) for controls (p < 0.001). The five domains of the questionnaire also exhibited significant improvement in the therapy group: desire and interest (p = 0.003), foreplay (p = 0.003), excitation and tuning (p < 0.001), comfort (p < 0.001), and orgasm and satisfaction (p < 0.001)., Conclusion: Group CBT was shown to be an effective tool for treating HSDD., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Hypoactive sexual desire disorder (HSDD) is a common female sexual dysfunction and is estimated to affect approximately 10% of women in the United States. It has been suggested that HSDD is associated with an imbalance of hormone and neurotransmitter levels in the brain, resulting in decreased excitation, increased inhibition, or a combination of both. Evidence suggests neurotransmitters, including dopamine (DA), norepinephrine, and serotonin, as well as hormones such as estradiol and testosterone, contribute to female sexual desire and response. Current treatments for HSDD include psychotherapy, and two US Food and Drug Administration-approved medications for premenopausal women: flibanserin, a serotonin mixed agonist and antagonist, and bremelanotide, a melanocortin receptor (MCR) agonist. Melanocortins are endogenous neuropeptides associated with the excitatory pathway of the female sexual response system. MCRs are found throughout the body, including the brain. Bremelanotide is an MCR agonist that nonselectively activates several of the receptor subtypes, of which subtype 4 (MC4R) is the most relevant at therapeutic doses. MC4R is predominantly expressed in the medial preoptic area (mPOA) of the hypothalamus in the brain, and is important for female sexual function. Animal studies suggest that bremelanotide may affect female sexual desire by activating presynaptic MC4Rs on neurons in the mPOA of the hypothalamus, leading to increased release of DA, an excitatory neurotransmitter that increases sexual desire. This review presents what is known about the mechanism of action of bremelanotide in the context of treating HSDD.

Background: Hypoactive sexual desire disorder (HSDD), which affects ∼10% of women in the United States, is defined as the persistent or recurrent deficiency/absence of sexual desire accompanied by personal distress. Although HSDD impacts patient quality of life and interpersonal relationships, the disorder often goes unaddressed or untreated. Recent studies of the burden of illness in women with HSDD, especially premenopausal women, are limited. Materials and Methods: A 45-minute web-based survey was designed to investigate the experience of women seeking treatment for HSDD and the impact of this disorder on several psychosocial aspects of women's lives. Women were recruited from an online panel of patients who participated in research studies for compensation. Validated questionnaires assessed sexual function (Female Sexual Function Index) and health-related quality of life (12-Item Short Form Survey [SF-12]), including mental and physical component scores. Results: A total of 530 women, aged ≥18 years, diagnosed with acquired generalized HSDD were included in the study. Premenopausal women indicated greater overall HSDD symptom burden compared with postmenopausal women. Patients with HSDD reported lower SF-12 scores compared with the general population. A multivariable regression analysis demonstrated that psychosocial factors influencing the burden of HSDD, including interference with their relationship with their partner (β = -0.18; p  < 0.005), mental and emotional well-being (β = -0.23; p  < 0.005), and household and personal activities (β = -0.23; p  = 0.02), negatively affected SF-12 mental component scores. Conclusions: HSDD symptom burden was found to be negatively and statistically significantly associated with patients' mental health; the impact was greater among premenopausal women compared with postmenopausal women.

Female sexual dysfunction (FSD) comprises multiple overlapping sexual disorders with a multifaceted cause within the frame of the biopsychosocial model. Health care providers can screen for FSD according to their level of expertise and deliver at least basic counseling before eventually referring to sexual medicine specialists for specific care. The therapeutic algorithm comprises a multidisciplinary approach, including pharmacologic and nonpharmacologic management. Flibanserin and bremelanotide are psychoactive agents indicated for the treatment of generalized acquired hypoactive sexual desire disorder (HSDD) in premenopausal women, whereas transdermal testosterone is effective on HSDD in postmenopausal women. Menopause hormone therapy (systemic and local) is the mainstay for individualized management of women at midlife., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Hypoactive sexual desire disorder (HSDD), the most prevalent female sexual dysfunction, is characterized as persistent diminished desire for sexual activity accompanied by distress. The efficacy and safety of bremelanotide, a melanocortin receptor agonist approved by the U.S. Food and Drug Administration for treatment of acquired generalized HSDD in premenopausal women, were established in the phase 3 RECONNECT studies, two identically designed double-blind randomized placebo-controlled studies with an optional 52-week open-label extension. This report investigates efficacy of bremelanotide versus placebo according to prespecified subgroups (age, weight, body mass index [BMI], and bioavailable testosterone) in the RECONNECT studies. Materials and Methods: Patients self-administered bremelanotide 1.75 mg or placebo subcutaneously using an autoinjector, as needed, before sexual activity for 24 weeks. Efficacy was assessed using change from baseline to end-of-study for Female Sexual Function Index desire domain and Female Sexual Distress Scale-Desire/Arousal/Orgasm Item 13 for bremelanotide versus placebo. Results: Among 1202 patients included in the integrated and subgroup analyses, bremelanotide achieved statistically significant improvements in measures of increased desire and decreased distress associated with low desire across all age, weight, and BMI subgroups, and all baseline bioavailable testosterone quartiles, with few exceptions. Bremelanotide was further associated with statistically significant increases in reported sexual desire ( p  < 0.05) in patients not taking hormonal contraceptives, and with a numerical advantage in those taking hormonal contraceptives. Patients treated with bremelanotide experienced decreased distress compared with those in the placebo group at levels of statistical significance ( p  < 0.05) regardless of hormonal contraceptive use. Statistically significant improvements were observed in the presence or absence of decreased arousal, and regardless of HSDD duration. Conclusions: Bremelanotide was associated with statistically significant improvements in sexual desire and reduced distress across several prespecified subgroups, with few exceptions.

Background: The 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., Aim: Evaluate clinically meaningful benefit of flibanserin., Methods: Data 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., Outcomes: PGI-I, anchor-based analyses for key efficacy endpoints (SSE, FSFI-d, FSDS-R13), odds ratios, onset time for treatment benefit., Results: Based 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 Implications: Patient-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 Limitations: Strengths 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., Conclusion: Assessment 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., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Bremelanotide, a melanocortin receptor agonist, is Food and Drug Administration (FDA)-approved for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder. Methods: Review of bremelanotide's safety profile from the clinical development program (phases 1 through 3). Results: The clinical development program comprised 3500 subjects in 43 completed studies. In the phase 3 studies, subjects took bremelanotide for up to 18 months. The most common adverse events (AEs) were nausea (40.0% vs. 1.3%), flushing (20.3% vs. 1.3%), headache (11.3% vs. 1.9%), and injection site reactions (5.4 vs. 0.5), bremelanotide versus placebo groups, respectively, in the integrated double-blind portion of the phase 3 studies ( N  = 1247). Nausea was the most common reason for bremelanotide discontinuation. There were no deaths; a few subjects experienced serious AEs. Focal hyperpigmentation was rare when bremelanotide was dosed in accordance with label recommendations, but it occurred in more than one-third of subjects following up to 16 consecutive daily dosings. Small and transient but statistically significant blood pressure increases were observed during ambulatory blood pressure monitoring. Most drug-drug interactions were not clinically significant, except for interactions that lowered plasma concentrations of indomethacin and naltrexone. In the double-blind portion of the integrated phase 3 studies, 70% of the bremelanotide group proceeded to the open-label phase of the studies versus 87% of those on placebo. Conclusions: The AEs associated with bremelanotide are mostly mild to moderate. Although not deemed clinically important, bremelanotide should be used with caution in patients at risk of cardiovascular disease, and blood pressure should be well controlled during treatment. Clinical Trial Registration number: NCT02333071 [Study 301] and NCT02338960 [Study 302].

Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD.

Introduction: Hypoactive Sexual Desire Disorder (HSDD) / Female Sexual Interest/Arousal Disorder (FSIAD) impacts health-related quality of life (HRQoL) of women and their partners, yet existing measures fail to adequately capture relevant concepts (ie, what is essential to measure including symptoms/impacts) important to women with HSDD/FSIAD., Objectives: To identify HRQoL tools used to assess women with HSDD/FSIAD, and to evaluate their psychometric properties (ie, reliability, validity, and responsiveness)., Methods: We conducted searches in PubMed, Embase and PsychINFO from June 5, 1989 to September 30, 2020 for studies in women with HSDD/FSIAD and psychometric analyses (English only). Principles of the Preferred Reporting Items for Systematic reviews and Meta-Analyses, the COnsensus-based Standards for the selection of health Measurement INstruments Risk of Bias Checklist and other psychometric criteria were applied. Based on this search, 56 papers were evaluated including 15 randomized-controlled trials, 11 observational/single arm/open label studies, and 30 psychometric studies., Results: Of the 18 measures identified, the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised (FSDS-R) were included in most studies (> 50%). General HRQoL instruments were not used in any of the clinical trials; the SF-12, SF-36 and EQ-5D-5L were reported in two observational studies. No instruments achieved positive quality ratings across all psychometric criteria. The FSFI, FSDS-R, Sexual Event Diary (SED) and the Sexual Desire Relationship Distress Scale (SDRDS), were the only measures to receive a positive rating for content validity., Conclusion: Reliable and valid HRQoL measures that include sexual desire and distress are needed to provide a more systematic and comprehensive assessment of HRQoL and treatment benefits in women with HSDD/FSIAD. While inferences about HRQoL are limited due to the lack of uniformity in concepts assessed and limited psychometric evaluation of these measures in women with HSDD/FSIAD, opportunities exist for the development of reliable and validated tools that comprehensively measure the most relevant and important concepts in women with HSDD/FSIAD. Lim-Watson MZ, Hays RD, Kingsberg S, et al. A systematic literature review of health-related quality of life measures for women with Hypoactive Sexual Desire Disorder and Female Sexual Interest/Arousal Disorder. Sex Med Rev 2022;10:23-41., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Female sexual dysfunction (FSD) is an underinvestigated comorbidity of diabetes mellitus, often not evaluated in diabetes clinics. Diabetic women should be encouraged to talk about this topic by their diabetologist, because these problems could be comorbid to cardio-metabolic alterations, as it happens in the male counterpart. This review summarizes evidence on sexual dysfunction characteristics in diabetic women, exploring possible underlying pathogenic mechanisms. The role of hypoglycemic drugs in this context was also evaluated. To date, no specific questionnaire has been designed for the assessment of sexual dysfunctions in diabetic female patients but the use of colour-doppler ultrasound of clitoral arteries has been highlighted as a useful tool for the assessment of cardiovascular risk in these women. Similarly, no specific guidelines are available for the treatment of FSD in the diabetic population but patients should be supported to have a healthy lifestyle and, in the absence of contraindications, can benefit from already approved treatments for FSD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In January 2022, the classification of female sexual dysfunctions under the new eleventh revision of International Classification of Diseases came into force. Its definitive integration into practice is expected after a 5-year transition period. The new nomenclature is based on a circular model of female sexual activity, eliminating the Cartesian-dualistic concept of separating individual pathophysiological entities with „non-organic“ and „organic“ etiology. Sexual dysfunctions are evaluated as a complex interaction of psychological, interpersonal, social, cultural, physiological, and by gender-related processes. The new 11th revision of International Classification of Diseases established clear criteria for symptomatology and duration of disorders according to duration, frequency, and exposure to distress. Female sexual dysfunctions may be diagnosed regardless of etiology. The system of qualifiers allows the identification of etiological factors related to health condition; psychological and mental disorders; use of psychoactive substances or medication; lack of knowledge or experience; relational, cultural or gender-related factors. This article summarizes the current situation in the classification of female sexual dysfunctions in a historical context and presents the modus operandi for clinical practice according to current classifications.

Aim: To provide a clinical practice guideline for the use of testosterone including identification of patients, laboratory testing, dosing, post-treatment monitoring, and follow-up care in women with hypoactive sexual desire disorder (HSDD)., Methods: The International Society for the Study of Women's Sexual Health appointed a multidisciplinary panel of experts who performed a literature review of original research, meta-analyses, review papers, and consensus guidelines regarding testosterone use in women. Consensus was reached using a modified Delphi method., Outcomes: A clinically useful guideline following a biopsychosocial assessment and treatment approach for the safe and efficacious use of testosterone in women with HSDD was developed including measurement, indications, formulations, prescribing, dosing, monitoring, and follow-up., Results: Although the Global Position Statement endorses testosterone therapy for only postmenopausal women, limited data also support the use in late reproductive age premenopausal women, consistent with the International Society for the Study of Women's Sexual Health Process of Care for the Management of HSDD. Systemic transdermal testosterone is recommended for women with HSDD not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. Current available research supports a moderate therapeutic benefit. Safety data show no serious adverse events with physiologic testosterone use, but long-term safety has not been established. Before initiation of therapy, clinicians should provide an informed consent. Shared decision-making involves a comprehensive discussion of off-label use, as well as benefits and risks. A total testosterone level should not be used to diagnose HSDD, but as a baseline for monitoring. Government-approved transdermal male formulations can be used cautiously with dosing appropriate for women. Patients should be assessed for signs of androgen excess and total testosterone levels monitored to maintain concentrations in the physiologic premenopausal range. Compounded products cannot be recommended because of the lack of efficacy and safety data., Clinical Implications: This clinical practice guideline provides standards for safely prescribing testosterone to women with HSDD, including identification of appropriate patients, dosing, and monitoring., Strengths and Limitations: This evidence-based guideline builds on a recently published comprehensive meta-analysis and the Global Position Statement endorsed by numerous societies. The limitation is that testosterone therapy is not approved for women by most regulatory agencies, thereby making prescribing and proper dosing challenging., Conclusion: Despite substantial evidence regarding safety, efficacy, and clinical use, access to testosterone therapy for the treatment of HSDD in women remains a significant unmet need.

Nearly half of women in the United States report problems with sexual function. Many health care providers do not ask about sexual concerns during routine clinical encounters because of personal discomfort, lack of familiarity with treatment, or the belief that they lack adequate time to address this complex issue. This may be especially true for hypoactive sexual desire disorder (HSDD), the most commonly identified sexual problem among women. HSDD is characterized by a deficiency of sexual thoughts, feelings, or receptiveness to sexual stimulation that has been present for at least 6 months, causes personal distress, and is not due to another medical condition. This is an up-to-date overview of HSDD for clinicians, discussing its physiology, assessment, diagnosis, and treatment strategies. Although a definitive physiology of HSDD is still unknown, multiple hormones and neurotransmitters likely participate in a dual-control model to balance excitation and inhibition of sexual desire. For assessment and diagnosis, validated screening tools are discussed, and the importance of a biopsychosocial assessment is emphasized, with guidance on how this can be implemented in clinical encounters. The 2 recently approved medications for HSDD, flibanserin and bremelanotide, are reviewed as well as off-label treatments. Overall, HSDD represents a common yet likely underrecognized disorder that midwives and other health care providers who care for women across the life span are in a unique position to address., (© 2021 by the American College of Nurse-Midwives.)

Objective: Provide strategies for improving the care of perimenopausal and postmenopausal women based on the most recent published evidence., Target Population: Perimenopausal and postmenopausal women., Benefits, Harms, and Costs: Target population will benefit from the most recent published scientific evidence provided via the information from their health care provider. No harms or costs are involved with this information since women will have the opportunity to choose among the different therapeutic options for the management of the symptoms and morbidities associated with menopause, including the option to choose no treatment., Evidence: Databases consulted were PubMed, MEDLINE, and the Cochrane Library for the years 2002-2020, and MeSH search terms were specific for each topic developed through the 7 chapters., Validation Methods: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: physicians, including gynaecologists, obstetricians, family physicians, internists, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; pharmacists; medical trainees, including medical students, residents, fellows; and other providers of health care for the target population., Summary Statements: RECOMMENDATIONS., (Copyright © 2021. Published by Elsevier Inc.)

Background: Hypoactive sexual desire disorder (HSDD) has a significant negative impact on women's overall health and relationships with their partners. Primary analyses from the RECONNECT clinical trials demonstrated statistically significant and clinically meaningful improvements in sexual desire and related distress with bremelanotide relative to placebo in premenopausal women with HSDD. Exit surveys and patient interviews were conducted to evaluate the impact of HSDD and bremelanotide treatment from the patient's perspective. Materials and Methods: Upon completion of the double-blind study but before participation in the open-label extension, up to 250 participants were recruited to complete the quantitative exit survey (17 questions). A subset of up to 90 patients was invited to participate in the telephone interview (17 questions). Patients who volunteered to participate remained blinded to study drug until the survey and interviews were completed. Results: Quantitative exit surveys were completed by 242 RECONNECT participants; 80 of these women also completed qualitative telephone exit interviews. Participants who received bremelanotide described increased feelings of sexual desire, physical arousal, and improvements in overall quality of their sexual activities in their partner relationship. In comparison, women taking placebo reported benefits that did not include the physiological responses described by women receiving bremelanotide, such as positive experiences of seeking HSDD treatment and improved communication with their partner. Conclusions: Exit surveys and patient interviews support the primary findings from RECONNECT and provide quantitative and qualitative assessments of the impact of HSDD on patients' quality of life and the patients' perspectives on the impact of bremelanotide. Clinical trial numbers NCT02333071, NCT02338960.

This systematic review evaluates the efficacy and safety of l-arginine alone or in combination for the treatment of women with hypoactive sexual desire disorder (HSDD) or related conditions, such as female sexual interest/arousal disorder and female sexual arousal disorder. Medline, Embase, International Pharmaceutical Abstracts, Science Direct, and the Cumulative Index to Nursing and Allied Health Literature were searched using keywords "arginine", "Lady Prelox", "ArginMax", "Stronvivo", "Ristela", "hypoactive sexual desire disorder", "female sexual interest arousal disorder", "female sexual arousal disorder", "sexual dysfunction", "sexual behavior", "dyspareunia", "libido", and permutations thereof. Relevant records were retained if they were primary literature, conducted in women with HSDD or related conditions, and published as full text in English. Five randomized controlled trials and two nonrandomized studies met eligibility criteria. Six of the seven studies reported either an increase in the total mean Female Sexual Function Index score or significant increases in multiple domains therein. One study assessed vaginal pulse amplitude and found a statistically significant increase in a combination treatment group compared to placebo. No significant side effects were reported. Four of seven studies had potential risk-of-bias concerns per Cochrane assessments. This systematic review found that combination products containing l-arginine in the form of ArginMax or Lady Prelox may be considered for the treatment of HSDD and related conditions in women regardless of age.

Transdermal testosterone therapy, dosed within premenopausal physiologic testosterone ranges, used alone or with menopausal hormone therapy for postmenopausal hypoactive sexual desire disorder, has shown short-term efficacy, with few androgenic side effects. After natural or surgical menopause, meaningful improvements include an additional satisfying sexual episode per month; improvement in desire, arousal, orgasm, pleasure, and responsiveness; and a reduction in distress. Long-term data on cardiovascular, cancer, and cognitive safety are lacking. No approved testosterone preparation is available for women. Compounded testosterone creams or reduced dosing of male-approved therapies represent off-label use. Injections or pellets cause supraphysiological testosterone levels and are not recommended., Competing Interests: Disclosure J.V. Pinkerton—none in past 24 months. I. Blackman—no disclosures. E.A. Conner—no disclosures. A.M. Kaunitz: Advisory Boards: Mithra, Pfizer; Clinical trials (financial support to University of Florida): Mithra., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hypoactive sexual desire disorder (HSDD) is a persistent or recurrent absence of sexual fantasies and desire for sexual activity, causing marked personal distress or interpersonal difficulties. HSDD affects 10% of U.S. women and is associated with depression and other negative emotional states. It is imperative that psychiatrists are competent to make this diagnosis and are aware of available treatment options. A full psychiatric and medical history are necessary to identify potential causes or contributing factors that may need to be addressed first. The authors discuss the diagnostic tools available as well as general diagnostic considerations for psychiatrists. Given its importance in the understanding of the available treatments for this disorder, the pathophysiology behind HSDD is reviewed. The authors emphasize the treatment of HSDD, including general treatment considerations, treatment in the context of depression, and psychotherapy and medications that have been approved by the U.S. Food and Drug Administration., (Copyright © by the American Psychiatric Association.)

Introduction: The 2 most well-known classification systems that include sexual medicine diagnoses are the International Classification of Diseases and Statistics (ICD) and the Diagnostic and Statistical Manual of Mental Disorders (DSM). Sexual medicine experts from international societies representing an array of disciplines have revised and redefined female sexual dysfunctions (FSDs) to reflect current scientific evidence and the state of the art., Aim: To summarize the evidence and interactive and chronological process by which sexual medicine societies' consensus groups developed the current nomenclature, classifications, and definitions for FSDs., Methods: We review the contributions and collaborations of the Fourth International Consultation in Sexual Medicine (ICSM), the International Society for the Study of Women's Sexual Health (ISSWSH), and the World Association of Sexual Health in conjunction with the World Health Organization., Main Outcome Measures: The ICSM and ISSWSH diagnostic systems are contrasted with the DSM classification. We discuss innovations and strengths; relevant evidence regarding epidemiology, etiology, and risk factors; and key differences. We describe how sexual medicine expertise informed FSD codes in the ICD-11 classification., Results: ICSM and ISSWSH published evidence-based guidelines on the definitions, nomenclature, and diagnostic criteria for FSD that diverge from the DSM psychiatric compendia. These definitions and nomenclature recommend the separation of female sexual desire and arousal disorders, elaborate on subtypes of arousal problems, broaden the scope of sexual pain definitions, and provide a greater understanding of etiologies and risk factors for FSDs., Conclusions: These collaborations among sexual medicine experts and their role in the ICD-11 development process provide confidence that the ICD-11 Sexual Dysfunction codes are based on current scientific evidence for diagnosing and coding FSDs in clinical settings worldwide, can serve as endpoints in clinical trials, and will provide specificity for treatment outcomes for FSD therapies. Parish SJ, Cottler-Casanova S, Clayton AH, et al. The Evolution of the Female Sexual Disorder/Dysfunction Definitions, Nomenclature, and Classifications: A Review of DSM, ICSM, ISSWSH, and ICD. Sex Med 2021;9:36-56., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The Elements of Desire Questionnaire (EDQ) is a patient-reported outcome (PRO) measure developed to evaluate sexual desire and was included in two identically designed phase 3 clinical trials (RECONNECT) as an exploratory endpoint. The EDQ was developed based on a literature review, qualitative research with patients with hypoactive sexual desire disorder (HSDD), and input from clinical experts. This instrument is intended to be used to collect efficacy data in clinical trials evaluating potential treatments for HSDD. The objective of this study was to evaluate the measurement properties of both the monthly and daily recall versions of the EDQ during the RECONNECT trials., Methods: Participants completed the EDQ daily version for 7 consecutive days prior to selected monthly clinic visits. The monthly recall version was completed at each monthly clinic visit. The analysis population consisted of all subjects with Female Sexual Function Index (FSFI) data at baseline and ≥ 1 follow-up visit., Results: At baseline, 1144 and 676 subjects completed the monthly and daily recall EDQs, respectively. The EDQ scores had good internal consistency and test-retest reliability. Monthly and daily recall EDQ scores were correlated with FSFI-desire domain scores at baseline and month 3. Scores from the monthly and daily recall versions were also correlated. After 6 months, there was a significantly greater improvement for bremelanotide versus placebo in both the monthly and daily recall versions (both P < 0.0001)., Conclusions: The results demonstrated that EDQ exhibited good reliability, validity, and sensitivity to change. Consistent with other validated PRO measures of sexual desire, the EDQ provides additional insights into sexual desire., Trial Registration: NCT02338960 and NCT02333071 (RECONNECT studies).

Aims: To evaluate the prevalence of hypoactive sexual desire disorder (HSDD) among postmenopausal women diagnosed with metabolic syndrome (MS) and to compare it to that of a control group without MS., Methods: This is a cross-sectional study carried out in 2 public tertiary hospitals in the state of São Paulo, Brazil, with a sample of 291 postmenopausal women aged between 40 and 65 years. Sexual function was evaluated using the Female Sexual Function Index (FSFI) questionnaire and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, diagnostic criteria and was related to the diagnosis of MS, which was determined according to the guidelines defined by the Adult Treatment Panel., Main Outcome Measures: Analysis of sexual function with emphasis on sexual desire (HSDD), the incidence of MS, and the components of MS., Results: The prevalence of HSDD was significantly higher among women diagnosed with MS than among women without MS (P = .01). Women diagnosed with high blood pressure (P < .01) and increased triglycerides (P = .03) also had a higher prevalence of HSDD than did women without these conditions. The FSFI domain scores for desire, arousal, lubrication, orgasm, and satisfaction and the total FSFI score were significantly lower for postmenopausal women with MS, whereas the pain domain score was not significantly different between the groups (P = .913). The incidence of female sexual dysfunction was significantly higher among women with MS, regardless of the diagnostic criteria used (P < .05)., Conclusion: Postmenopausal women diagnosed with MS have higher rates of HSDD than do women without MS., Clinical Trial Registration: ID NCT02430987. Dutra da Silva GM, Rolim Rosa Lima SM, Reis BF, et al. Prevalence of Hypoactive Sexual Desire Disorder Among Sexually Active Postmenopausal Women With Metabolic Syndrome at a Public Hospital Clinic in Brazil: A Cross-sectional Study. J Sex Med 2020;8:545-553., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Hypoactive sexual desire disorder (HSDD) in women is defined as the persistent or recurrent absence of sexual thoughts or fantasies and/or lack of desire for sexual activity that is associated with marked personal distress and/or interpersonal difficulties, and cannot be better attributed to another primary disorder, medication, or general medical condition. Notably, HSDD shares some similarity with depression, as its etiology can be explained using a biopsychosocial model that includes biological, psychological, and sociocultural factors, as well as interpersonal influences. Due to its high prevalence and negative impact on the overall health and well-being of women, primary care health professionals and women's health practitioners need to be actively aware of HSDD, particularly because patients may be reluctant or unwilling to initiate a discussion about their sexual concerns during routine visits. HSDD is well established as a valid and treatable clinical entity. Even for those inexperienced in treating sexual problems, there are simple and validated screening tools such as the Decreased Sexual Desire Screener that can help identify HSDD and a need for further evaluation and treatment. There have been few established pharmacologic treatments for HSDD. Flibanserin was the first drug approved for the treatment of HSDD by the U.S. Food and Drug Administration (FDA). Bremelanotide, a novel melanocortin receptor agonist, was recently approved by the FDA for the treatment of acquired, generalized HSDD in premenopausal women. Increased awareness and recognition of HSDD as a medical condition should provide an incentive for further clinical development of effective treatments for HSDD.

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.

Objective: Hypoactive sexual desire disorder (HSDD) in women has been viewed inaccurately by some in the medical and payer community as analogous to erectile dysfunction (ED) in men. This literature review aims to highlight the distinctions between HSDD and ED. Methods: Two systematic literature searches were conducted on the epidemiology, symptomatology and biopsychosocial outcomes of HSDD and ED. Studies published since 2007 were considered for HSDD; studies published since 2012 were considered for ED. Results: HSDD in women is primarily a central nervous system condition related to neuroendocrine factors, whereby neural pathways that regulate sexual excitation and/or inhibition appear to be involved. A combination of organic and psychogenic factors often contributes to ED. HSDD and ED are associated with similar psychological and interpersonal consequences, but affect different phases of the sexual response model (desire versus arousal) and have different pathophysiologies, therefore requiring different treatment and outcome paradigms. ED is measured by objective, physiological responses (erection and sexual function), but quantitative assessments for HSDD are more difficult because loss of desire with associated distress has to be assessed. Outcome measures used to assess ED, such as the number of satisfying sexual events, are far less informative as an endpoint for randomized clinical trials of treatments for HSDD. Conclusions: HSDD and ED are distinct conditions affecting different phases of the sexual response model, and thus require clear and unique clinical characterization and adequate communication between the health care professional and patient for appropriate diagnosis, management and treatment.

Objective: Hypoactive Sexual Desire Disorder (HSDD) among women is a complicated one which is created by various factors playing roles. One of the potential concerns related to Body Image (BI) is lack of sexual appeal in women. Body Image is often described as what a person perceives of their body encompassing the biological, psychological and social factors. The present research pursues the goal to investigate the association between BI and HSDD among the reproductive age women in Iran. Materials and methods: The current study is a cross-sectional (descriptive -analytical) research done on 1000 reproductive age included woman (15-49 years), performed by systematic random sampling method. The data collection tool includes the socio-demographics and the sexual desire scale in addition to the revised sexual distress scale to measure HSDD completed as self-report by the samples. Univariate and multivariate regression tests have been used in order to analyze the data. Results: The mean ± SD age of the women participating in the study was 32.09 ± 7.33. Having adjusted the confounder variables' effect by logistic regression multivariate analysis; the odd ratio for HSDD has been analyzed. The findings suggested that the odd ratio for HSDD in those not satisfied or slightly feeling fulfilled with their BI has been OR: 4.2 (95% CI: 1.98-9.05) and OR: 3.9 (95% CI: 2.29-6.65), respectively, times more than the ones highly satisfied with their body image. Conclusion: The present study results indicate that being dissatisfied with BI is a determinant factor of HSDD that is more probable in the people with negative image of their body structure and feeling lack of bodily appeal. Thus it is imperative to pay attention to this factor when analyzing HSDD., (Copyright © Tehran University of Medical Sciences.)

Introduction: Sexual performance anxiety (SPA) is one of the most prevalent sexual complaints; yet, no diagnosis is recognized for either gender. Thus, research into treatment has been minimal., Aim: Review the prevalence of SPA and its relation to sexual dysfunctions and anxiety disorders. Compare SPA to (non-sexual) performance anxiety and social anxiety (PA/SA). Apply pharmacologic principles to the known properties of drugs and phytotherapies to hypothesize treatments for SPA., Methods: Review SPA and PA/SA through PubMed searches for relevant literature from 2000 to 2018., Main Outcome Measure: Prevalence was estimated using population-representative surveys. For treatment results, controlled clinical trial results were prioritized over open-label trial results., Results: SPA affects 9-25% of men and contributes to premature ejaculation and psychogenic erectile dysfunction (ED). SPA affects 6-16% of women and severely inhibits sexual desire. Cognitive behavior therapy and mindfulness meditation training have been proven effective for PA/SA and are recommended for SPA, but controlled studies are lacking. Phosphodiesterase type 5 inhibitors are effective for psychogenic ED and premature ejaculation, both of which include SPA as a major element. Drugs proven for PA/SA have adverse sexual and sedative effects, but serotonergic anxiolytics with prosexual effects (buspirone ± testosterone, trazodone ± bupropion) may have potential, and sage, passionflower, l-theanine, and bitter orange are anxiolytic. Nitric oxide boosters (l-citrulline, l-arginine, Panax ginseng) have the potential for increasing genital tumescence and lubrication, and plant-based alpha-adrenergic antagonists may aid sexual arousal (yohimbine/yohimbe, Citrus aurantium/p-synephrine)., Conclusion: SPA causes or maintains most common sexual dysfunction. No treatments are well proven, although cognitive behavior therapy, mindfulness meditation training, and serotonergic anxiolytics (buspirone, trazodone, gepirone) have potential, and phosphodiesterase type 5 inhibitors are effective for psychogenic ED and premature ejaculation. Several phytotherapies also appear to have potential. Pyke RE. Sexual Performance Anxiety. J Sex Med 2020;8:183-190., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction : Hypoactive sexual desire disorder (HSDD) is the most prevalent sexual dysfunction in women, previously managed with off-label therapies. Indicated for premenopausal women, flibanserin is the first FDA-approved medication to treat HSDD. Areas covered : This review summarizes flibanserin's pharmacokinetics, proposed mechanism of action, and safety data in clinical trials with a focus on sedation- and hypotension-related adverse events, and drug interactions with alcohol and antidepressants. Sources included peer-reviewed publications and internal data from the manufacturer. Expert opinion : Flibanserin is a well-tolerated and effective treatment that decreases distress and restores sexual desire to a level that is normative for the individual patient with HSDD. Simplification of a risk mitigation program for flibanserin in the US is likely to increase the number of prescribing clinicians if accompanied with educational efforts to clarify flibanserin's risk-benefit profile. As flibanserin is dosed daily and may be used for a decade or more in the typical premenopausal patient, long-term pharmacovigilance data will be essential. Over time, HSDD will be treated by more nonspecialist health care professionals and flibanserin will likely become established as a significant treatment option along with other medications approved for this indication in the context of a holistic biopsychosocial treatment paradigm.

Introduction: Flibanserin is approved in the United States and Canada for the treatment of hypoactive sexual desire disorder in premenopausal women., Aim: The purpose of this trial was to evaluate the safety of concomitant administration of flibanserin with alcohol., Methods: In this single-center, randomized, double-blind, single-dose, crossover study, participants were randomly assigned to 1 of 12 sequences to receive each of 7 treatments: flibanserin 100 mg or placebo with ethanol 0.2 g/kg, 0.4 g/kg, or 0.6 g/kg, or flibanserin 100 mg only. Treatments were administered using a worst-case approach that included morning dosing and consumption of alcohol within 10 minutes., Main Outcome Measure: The primary end point was the proportion of participants who experienced dizziness, syncope, or hypotension. Safety end points included orthostatic vital signs., Results: The study included 96 premenopausal women (mean age 31 ± 8 years). The incidence of dizziness for ethanol + flibanserin was 39.8% for ethanol 0.6 g/kg, 34.1% for 0.4 g/kg, and 27.4% for 0.2 g/kg compared with 31.1% for flibanserin without ethanol. Based on the available vital signs data, there was no effect of ethanol concentration on orthostatic blood pressure, vertigo, or hypotension; no instances of syncope were observed. The overall incidence of adverse events (AEs) was similar when flibanserin was administered alone (96.7%) or with ethanol (90.5-97.6%)., Clinical Implications: Consumption of the tested amounts of alcohol (0.2-0.6 g/kg) does not have an additive effect on the AE profile of flibanserin 100 mg in healthy premenopausal women., Strengths & Limitations: Strengths include the study population (premenopausal women, as indicated for flibanserin) and range of ethanol doses. Limitations include the morning dosing of study medication, which is inconsistent with the bedtime dosing recommended for flibanserin, and the method of handling missing vital sign measurements., Conclusion: Co-administration of flibanserin 100 mg with varying doses of ethanol resulted in few AEs of special interest, with no notable alcohol dose response. However, a significantly greater percentage of participants administered flibanserin with 0.6 g/kg and 0.4 g/kg of alcohol were characterized as "Participants in Whom Standing Blood Pressure Was Not Obtained" compared with participants administered flibanserin alone. Simon JA, Clayton AH, Parish SJ, et al. Effects of Alcohol Administered With Flibanserin in Healthy Premenopausal Women: A Randomized, Double-Blind, Single-Dose Crossover Study. J Sex Med 2020;17:83-93., (Copyright © 2019. Published by Elsevier Inc.)

Introduction: Flibanserin, a treatment for hypoactive sexual desire disorder, carries warnings for increased risk of severe hypotension and syncope when used with alcohol. However, these warnings are not informed by studies that used flibanserin's recommended bedtime dosing because previous alcohol studies assessed flibanserin's safety during the day., Aim: The aim of this study was to assess the effects of ethanol in a real-world context in premenopausal women taking flibanserin at bedtime., Methods: In a randomized, placebo-controlled, double-blind study, 24 healthy premenopausal women (mean age = 34.5 ± 9.9 years; mean body mass index = 25.2 ± 3.4 kg/m 2 ) were dosed with flibanserin or placebo for 3 days to achieve steady-state plasma levels. In a clinical research unit, subjects (n = 22) were provided 2 units of wine (150 mL/unit; 12% ethanol content) or a nonalcoholic beverage with a standardized 3-course evening meal. Flibanserin 100 mg or placebo was administered at bedtime 2.5 hours after the end of the evening meal. On a separate day, subjects were provided the alternative beverage (± alcohol) with the same evening meal and dosed with the same treatment (flibanserin or placebo) at bedtime. After a 5-day washout period, subjects crossed over to the other treatment arm and the protocol was repeated., Main Outcome Measure: Adverse events (AEs) and vital signs were monitored., Results: In the absence of ethanol, headaches and hypotension were the only AEs that occurred in ≥2 subjects after flibanserin dosing (placebo corrected rates were 17.4% and 8.7%, respectively). After ethanol consumption, the rate of hypotension after flibanserin dosing was no greater than with flibanserin or placebo after nonalcoholic beverage consumption. There were no instances of orthostatic hypotension or syncope and no serious AEs or AEs leading to study discontinuation., Conclusion: Flibanserin dosed at bedtime after moderate amounts of alcohol with an evening meal was well-tolerated with no evidence of clinically significant hypotension or syncope. Millheiser L, Clayton AH, Parish SJ, et al. Safety and Tolerability of Evening Ethanol Consumption and Bedtime Administration of Flibanserin in Healthy Premenopausal Female Subjects. Sex Med 2019;7:418-424., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Flibanserin is approved in the United States and Canada for the treatment of acquired, generalized, hypoactive sexual desire disorder in premenopausal women. Sedation-related side effects are among the most prevalent adverse events. Although infrequent, hypotension and syncope remain safety concerns because of possible interaction of flibanserin with alcohol., Aim: To evaluate the impact of the timing of alcohol consumption on flibanserin safety and tolerability., Methods: In this single-center, randomized, double-blind, placebo-controlled, 4-treatment crossover study, 64 healthy premenopausal women (mean age 32.5 ± 8.7 years; range 20‒52 years) received once-daily flibanserin 100 mg or placebo during each of two 10-day treatment periods. Study medication was administered on days 1-3 to achieve steady state. On days 4, 6, 8, and 10, after a standard breakfast, participants consumed 0.4 g/kg ethanol (approximately equivalent to two 5-oz glasses of wine) administered with orange juice 2, 4, or 6 hours before taking study medication or orange juice alone (no ethanol) 2 hours before taking study medication., Outcomes: The primary endpoint was percentage of participants experiencing syncope or orthostatic hypotension-associated adverse events requiring medical intervention. Secondary endpoints included the incidence of hypotension, the incidence of orthostatic hypotension, and rates of adverse events of special interest (syncope, orthostatic hypotension, dizziness, and somnolence)., Results: 1 participant experienced a primary endpoint event (syncope) during treatment with placebo taken 4 hours after ethanol consumption. Within each ethanol dose-timing treatment, there were no statistically significant differences for flibanserin compared with placebo. Rates of hypotension were 53.3-66.7% after flibanserin dosing and 57.4-63.3% after placebo dosing. Rates for orthostatic hypotension were 0.0-5.0% after flibanserin dosing and 1.7-6.6% after placebo dosing., Clinical Implications: Ethanol interaction with flibanserin was not observed in this study., Strengths & Limitations: This study provides information regarding the use of flibanserin after the consumption of moderate amounts of ethanol (0.4 g/kg). However, daytime administration of flibanserin is not consistent with the drug's indicated bedtime dosing., Conclusion: Flibanserin, at steady state taken 2, 4, or 6 hours after 0.4 g/kg of ethanol intake did not increase the incidence of hypotension, orthostatic hypotension, or syncope compared with either flibanserin alone or ethanol alone. Simon JA, Clayton AH, Kingsberg SA, et al. Effects of Timing of Flibanserin Administration Relative to Alcohol Intake in Healthy Premenopausal Women: A Randomized, Double-Blind, Crossover Study. J Sex Med 2019;16:1779-1786., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)