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A Qualitative Study of Women's Experiences with Hypoactive Sexual Desire Disorder in the United States
Abstract
Introduction
Hypoactive Sexual Desire Disorder (HSDD) significantly impacts a woman's daily functioning and well-being (health-related quality of life, HRQoL) and is often undetected by the medical profession and dismissed by society. As a result, the profound and extensive impact of HSDD on the lives of women and their partners is underappreciated.
Objective
This qualitative study was conducted to identify defining symptoms and HRQoL impacts among women with HSDD.
Methods
Six virtual focus groups (90-minutes each) were conducted with 30 adult women to understand HSDD symptoms and HRQoL impacts. Two trained focus group moderators utilized a semi-structured interview guide to capture spontaneous and stated symptoms and impacts. All focus groups were transcribed verbatim, anonymized, coded by two independent researchers using Atlas.ti 9, and then analyzed employing a combination of semi-quantitative and qualitative data analytic methods to evaluate saturation. Elicited content was used to further refine a literature-derived HRQoL conceptual model of HSDD.
Results
A total of 15 pre-menopausal and 15 post-menopausal women participated in the focus groups between October 14 and 21, 2020. Participants reported a total of 10 symptom concepts during the focus group, including loss of spontaneous desire, sexual distress, disinterest in initiating sex, disinterest in engaging in sex, absence of pleasure, little to no sexy feelings, feeling asexual, sexual avolition, vaginal pain, and insomnia. The most frequently reported symptoms were loss of spontaneous desire (n=30, 100%) and sexual distress (n=23, 77%). A total of 41 impact concepts associated with HSDD across 9 domains were reported: partner impact, mental well-being, role functioning, social functioning, familial relationships, appearance, concentration, and overall quality of life and satisfaction with life. Women reported impairment to their mental well-being (n=30, 100%), partner relationship (n=29, 97%), overall quality of life (n=29, 97%), and life satisfaction (n=29, 97%), as well as described feeling stigmatized by healthcare providers, friends, and society as a whole (n=27, 90%). A literature-based conceptual model for HSDD was updated to reflect focus group results.
Conclusions
Women with HSDD report many relevant, important, and meaningful concepts that are inadequately evaluated in research and drug trials. HSDD profoundly and negatively impacts women's HRQoL. Greater awareness of these concepts, and the availability of HRQoL measures that accurately reflect symptoms and impacts are needed to “destigmatize” and improve medical care for women with HSDD.
Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: AMAG Pharmaceuticals, Inc., Astellas, Dare, Duchesnay, Ovoca, Field Trip, Palatin Technologies, Pfizer, Materna, Maddora, TherapeuticsMD, Strategic Science Technologies, and Lupin.
ResearchGate has not been able to resolve any citations for this publication.
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.
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).
Objective:
To evaluate the long-term safety and efficacy of bremelanotide as treatment for hypoactive sexual desire disorder in premenopausal women.
Methods:
Women who completed the 24-week double-blind core phase of RECONNECT, composed of two parallel phase 3 trials (301 and 302) examining the safety and efficacy of bremelanotide compared with placebo in premenopausal women with hypoactive sexual desire disorder, could enroll in the 52-week open-label extension, provided they had not experienced serious adverse events during the core phase. Efficacy was assessed using the coprimary endpoints from the core phase, and all adverse events were collected during the open-label extension. All statistical analyses were descriptive.
Results:
The study 301 open-label extension began on July 17, 2015, and concluded on July 13, 2017; the study 302 open-label extension began on October 5, 2015, and concluded on June 29, 2017. Of the 856 eligible patients who completed the core phase, 684 elected to participate in the open-label extension, and 272 completed it. The most common treatment-emergent adverse events considered related to study drug were nausea (40.4%), flushing (20.6%), and headache (12.0%), and the only severe treatment-emergent adverse event experienced by more than one participant in both studies was nausea during the open-label extension. The change in Female Sexual Function Index-desire domain score and Female Sexual Distress Scale-Desire/Arousal/Orgasm item 13 from baseline to end of the open-label extension ranged from 1.25 to 1.30 and -1.4 to -1.7, respectively, for patients who received bremelanotide during the core phase, and 0.70-0.77 and -0.9, respectively, for patients who received placebo during the core phase.
Conclusion:
During the 52-week open-label extension of RECONNECT, no new safety signals were observed, and premenopausal women treated with bremelanotide exhibited sustained improvements in hypoactive sexual desire disorder symptoms.
Clinical trial registration:
ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302).
Funding source:
Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.
Objective:
To evaluate the safety and efficacy of bremelanotide for the treatment of premenopausal women with hypoactive sexual desire disorder.
Methods:
Two identical phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trials (RECONNECT) evaluated the safety and efficacy of bremelanotide 1.75 mg administered subcutaneously as needed in premenopausal women with hypoactive sexual desire disorder. Patients were randomized 1:1 to 24 weeks of treatment with bremelanotide or placebo. Sample size was estimated based on simulations from key endpoints in patients with hypoactive sexual desire disorder from a prior trial. Coprimary efficacy endpoints were change from baseline to end-of-study in the Female Sexual Function Index-desire domain score and Female Sexual Distress Scale-Desire/Arousal/Orgasm item 13.
Results:
Study 301 began on January 7, 2015, and concluded on July 26, 2016. Study 302 began on January 28, 2015, and concluded on August 4, 2016. Of the 1,267 women randomized, 1,247 and 1,202 were in the safety and efficacy (modified intent-to-treat) populations, respectively. Most participants were white (85.6%), from U.S. sites (96.6%), and had a mean age of 39 years. From baseline to end-of-study, women taking bremelanotide had statistically significant increases in sexual desire (study 301: 0.30, P<.001; study 302: 0.42, P<.001; integrated studies 0.35, P<.001) and statistically significant reductions in distress related to low sexual desire (study 301: -0.37, P<.001; study 302: -0.29, P=.005; integrated studies -0.33, P<.001) compared with placebo. Patients taking bremelanotide experienced more nausea, flushing, and headache (10% or more in both studies) compared with placebo.
Conclusions:
Both studies demonstrated that bremelanotide significantly improved sexual desire and related distress in premenopausal women with hypoactive sexual desire disorder. The safety profile was favorable. Most treatment-emergent adverse events were related to tolerability and the majority were mild or moderate in intensity.
Clinical trial registration:
ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302).
Funding source:
Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.
Background:
Efficacy of on-demand drugs for women with hypoactive sexual desire disorder or female sexual interest/arousal disorder (FSIAD) should be assessed using a validated instrument that assesses the discrete sexual events during which the on-demand drug is taken, because this type of assessment is more proximate to an on-demand drug's efficacy compared to instruments that assess sexual function over longer periods of time.
Aim:
The aim of this study was to assess the psychometric properties of the Dutch translation of the previously validated 11-item Sexual Event Diary (SED) for measuring sexual satisfaction and sexual functioning during discrete sexual events.
Methods:
Psychometric assessment was performed on data of 1,840 SEDs from 139 women with hypoactive sexual desire disorder/FSIAD, collected during a randomized clinical cross-over trial conducted in the Netherlands.
Outcomes:
Item scores of the SED at the event level, and at subject level, summarized item scores during the placebo run-in period (PRI) and active treatment period, and score changes from PRI to active treatment period.
Results:
Reliability and convergent validity were confirmed. All item scores showed the ability to discriminate between known groups. Larger mean score changes from PRI were observed in groups with known benefit from the medication, as compared to those with no benefit. Guyatt effect sizes ranged from 0.51-1.02, thereby demonstrating ability to detect change.
Clinical translation:
The Dutch version of the SED is an excellent instrument for assessing female sexual functioning and sexual satisfaction during discrete sexual events and for assessing these concepts over longer periods of time.
Conclusions:
Data were collected in a randomized, well-controlled trial. The large number of data points gave high statistical power, and the results confirmed previous findings. However, care is needed when generalizing the SED's validity to other areas of research, eg, recreational drug use and sexual risky behaviors, since the current validation study has not used such data. Consistent with the US-English version, the Dutch version of the SED is a reliable, valid, and responsive instrument, and suitable for use in evaluating effects of on-demand drugs in women with FSIAD. van Nes Y, Bloemers J, Kessels R, et al. Psychometric Properties of the Sexual Event Diary in a Sample of Dutch Women With Female Sexual Interest/Arousal Disorder. J Sex Med 2018;15:722-731.
PurposeThe original COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was developed to assess the methodological quality of single studies on measurement properties of Patient-Reported Outcome Measures (PROMs). Now it is our aim to adapt the COSMIN checklist and its four-point rating system into a version exclusively for use in systematic reviews of PROMs, aiming to assess risk of bias of studies on measurement properties. Methods
For each standard (i.e., a design requirement or preferred statistical method), it was discussed within the COSMIN steering committee if and how it should be adapted. The adapted checklist was pilot-tested to strengthen content validity in a systematic review on the quality of PROMs for patients with hand osteoarthritis. ResultsMost important changes were the reordering of the measurement properties to be assessed in a systematic review of PROMs; the deletion of standards that concerned reporting issues and standards that not necessarily lead to biased results; the integration of standards on general requirements for studies on item response theory with standards for specific measurement properties; the recommendation to the review team to specify hypotheses for construct validity and responsiveness in advance, and subsequently the removal of the standards about formulating hypotheses; and the change in the labels of the four-point rating system. Conclusions
The COSMIN Risk of Bias checklist was developed exclusively for use in systematic reviews of PROMs to distinguish this application from other purposes of assessing the methodological quality of studies on measurement properties, such as guidance for designing or reporting a study on the measurement properties.
Background:
Hypoactive sexual desire disorder (HSDD) is a common sexual disorder in younger and older women. Flibanserin is approved for the treatment of acquired generalized HSDD in premenopausal women only. The efficacy of flibanserin for postmenopausal women with HSDD was demonstrated in the first of two North American randomized, double-blinded, placebo-controlled trials (SNOWDROP).
Aim:
To evaluate the safety and efficacy of flibanserin in postmenopausal women with HSDD in a second randomized, double-blinded, placebo-controlled trial (PLUMERIA).
Methods:
Naturally postmenopausal women were randomly assigned to receive flibanserin (100 mg/d) or placebo. Efficacy outcomes were assessed using the last-observation-carried-forward imputation method.
Outcomes:
Safety assessment included incidence of adverse events. Primary efficacy outcomes were the number of satisfying sexual events and the Female Sexual Function Index desire domain (FSFI-d) score.
Results:
The study population (flibanserin, n = 376; placebo, n = 369) included primarily white women (84.7%), with a mean age of 56.1 years and a mean HSDD duration of 5.0 years. When the study was discontinued early by the sponsor, 45.3% of randomly assigned patients had completed week 16 (which served as the primary analysis time point). The most common adverse events in flibanserin-treated patients were insomnia (7.7%), somnolence (6.9%), and dizziness (6.4%). Improvement from baseline to week 16 (last-observation-carried-forward) in FSFI-d score was significantly greater for flibanserin compared with placebo (P = .011); however, the between-group comparison for satisfying sexual events did not reach statistical significance.
Clinical implications:
Considered with the findings of the previous randomized controlled trial (SNOWDROP), the results of this study support the safety and efficacy of flibanserin in postmenopausal women.
Strengths and limitations:
This was a well-designed randomized, placebo-controlled trial. A key limitation was early discontinuation by the study sponsor, which decreased the sample size. In addition, the validity of satisfying sexual events as a primary outcome measurement in HSDD studies has been called into question (but was required by the US Food and Drug Administration as a primary end point in studies of female sexual dysfunction at the time this study was conducted).
Conclusion:
Flibanserin was generally well tolerated in this population of naturally postmenopausal women. Despite the greatly decreased power to detect improvement compared with placebo on the efficacy measurements used, results suggest that flibanserin could be efficacious in postmenopausal women with HSDD. Portman DJ, Brown L, Yuan J, et al. Flibanserin in Postmenopausal Women With Hypoactive Sexual Desire Disorder: Results of the PLUMERIA Study. J Sex Med 2017;14:834-842.
Purpose of Review
The dual control model of sexual response aims to explain sexual behavior and response through two factors, labeled sexual excitation and sexual inhibition. Sexual dysfunctions are common among women and men and pose a threat to the sexual health of both genders. The main objective of this paper was to review the latest findings concerning the predictive value of sexual excitation and sexual inhibition for sexual function and dysfunction in men and women.
Recent Findings
Most relevant studies have been conducted in North America and Europe using non-clinical samples. Women and men with high sexual inhibition related to performance concerns and distractibility during sex report lower sexual function. In addition, high sexual excitation is associated with higher sexual function in both genders.
Summary
Sexual excitation and sexual inhibition are predictors of sexual function in women and men. More prospective and clinical studies are needed to evaluate the usefulness of both propensities as predictors or moderators of treatment success.
Introduction
Although impaired sexual function is relatively common, not all sexual impairments are associated with distress. To date, most studies on protective and risk factors for sexual distress have asked about distress in a more general manner and have failed to distinguish different dimensions of sexual distress.
Aim
To examine the association of several intra- and interpersonal factors with personal, perceived partner, and interpersonal distress due to an impairment in sexual functioning in women.
Methods
This study is a cross-sectional representative population-based survey with a two-level random selection of Flemish women 14 to 80 years old from the Belgian National Register. The data of 520 sexually active heterosexual women with a partner (weighted N) and impairment in sexual desire (n = 291) and/or sexual arousal (n = 273) were used for analysis.
Main Outcome Measures
Demographic information was obtained, and the five-item Mental Health Inventory, the Marital Adjustment subscale of the Maudsley Marital Questionnaire, and the four-item Dyadic Sexual Communication Questionnaire were used. Presence and severity of sexual impairments and associated sexual distress were assessed using the Sexual Functioning Scale.
Results
Severity and number of sexual impairments were predictive of all types of sexual distress. Also, for desire and arousal impairments, lower mental well-being predicted personal distress, and lower relationship satisfaction predicted perceived partner distress. For desire impairments, lower relationship satisfaction and less communication about sexual needs were predictive of interpersonal distress. For impairments in sexual arousal, lower mental well-being and lower relationship satisfaction were predictive of interpersonal distress.
Conclusion
Personal, perceived partner, and interpersonal distress due to sexual impairments have different types of predictors. Clinical assessment and treatment could benefit from differentiating between different types of distress and the intra- and interpersonal factors that are associated with them.
Aim:
Evaluate efficacy/safety of bremelanotide (BMT), a melanocortin-receptor-4 agonist, to treat female sexual dysfunctions in premenopausal women.
Methods:
Patients randomized to receive placebo or BMT 0.75, 1.25 or 1.75 mg self-administered subcutaneously, as desired, over 12 weeks. Primary end point was change in satisfying sexual events/month. Secondary end points included total score changes on female sexual function index and female sexual distress scale-desire/arousal/orgasm.
Results:
Efficacy data, n = 327. For 1.25/1.75-mg pooled versus placebo, mean changes from baseline to study end were +0.7 versus +0.2 satisfying sexual events/month (p = 0.0180), +3.6 versus +1.9 female sexual function index total score (p = 0.0017), -11.1 versus -6.8 female sexual distress scale-desire/arousal/orgasm total score (p = 0.0014). Adverse events: nausea, flushing, headache.
Conclusion:
In premenopausal women with female sexual dysfunctions, self-administered, as desired, subcutaneous BMT was safe, effective, and well tolerated (NCT01382719).
Purpose:
Patient-reported data are playing an increasing role in health care. In oncology, data from quality of life (QoL) assessment tools may be particularly important for those with limited survival prospects, where treatments aim to prolong survival while maintaining or improving QoL. This paper examines the use and impact of using QoL measures on health care of cancer patients within a clinical setting, particularly those with brain cancer. It also examines facilitators and challenges, and provides implications for policy and practice.
Design:
We conducted a systematic literature review, 15 expert interviews and a consultation at an international summit.
Results:
The systematic review found no relevant intervention studies specifically in brain cancer patients, and after expanding our search to include other cancers, 15 relevant studies were identified. The evidence on the effectiveness of using QoL tools was inconsistent for patient management, but somewhat more consistent in favour of improving patient-physician communication. Interviews identified unharnessed potential and growing interest in QoL tool use and associated challenges to address.
Conclusion:
Our findings suggest that the use of QoL tools in cancer patients may improve patient-physician communication and have the potential to improve care, but the tools are not currently widely used in clinical practice (in brain cancer nor some other cancer contexts) although they are in clinical trials. There is a need for further research and stakeholder engagement on how QoL tools can achieve most impact across cancer and patient contexts. There is also a need for policy, health professional, research and patient communities to strengthen information exchange and debate, support awareness raising and provide training on tool design, use and interpretation.
How a woman responds to sexual cues is highly dependent on a number of distinct, yet related, factors. Researchers have attempted to explain the female sexual response for decades, but no single model reigns supreme. Proper female sexual function relies on the interplay of somatic, psychosocial and neurobiological factors; misregulation of any of these components could result in sexual dysfunction. The most common sexual dysfunction disorder is hypoactive sexual desire disorder (HSDD). HSDD is a disorder affecting women across the world; a recent in-person diagnostic interview study conducted in the USA found that an estimated 7.4 % of US women suffer from HSDD. Despite the disorder's prevalence, it is often overlooked as a formal diagnosis. In a survey of primary care physicians and obstetrics/gynaecology specialists, the number one reason for not assigning an HSDD diagnosis was the lack of a safe and effective therapy approved by the US Food and Drug Administration (FDA). This changed with the recent FDA approval of flibanserin (Addyi™) for the treatment of premenopausal women with acquired, generalized HSDD; there are still, however, no treatments approved outside the USA. HSDD is characterized by a marked decrease in sexual desire, an absence of motivation (also known as avolition) to engage in sexual activity, and the condition's hallmark symptom, marked patient distress. Research suggests that HSDD may arise from an imbalance of the excitatory and inhibitory neurobiological pathways that regulate the mammalian sexual response; top-down inhibition from the prefrontal cortex may be hyperactive, and/or bottom-up excitation to the limbic system may be hypoactive. Key neuromodulators for the excitatory pathways include norepinephrine, oxytocin, dopamine and melanocortins. Serotonin, opioids and endocannabinoids serve as key neuromodulators for the inhibitory pathways. Evolving treatment strategies have relied heavily on these crucial research findings, as many of the agents currently being investigated as treatment options for HSDD target and influence key players within these excitatory and inhibitory pathways, including various hormone therapies and centrally acting drugs, such as buspirone, bupropion and bremelanotide.
Background:
Systematic reviews of outcome measurement instruments are important tools for the selection of instruments for research and clinical practice. Our aim was to assess the quality of systematic reviews of health-related outcome measurement instruments and to determine whether the quality has improved since our previous study in 2007.
Methods:
A systematic literature search was performed in MEDLINE and EMBASE between July 1, 2013, and June 19, 2014. The quality of the reviews was rated using a study-specific checklist.
Results:
A total of 102 reviews were included. In many reviews the search strategy was considered not comprehensive; in only 59 % of the reviews a search was performed in EMBASE and in about half of the reviews there was doubt about the comprehensiveness of the search terms used for type of measurement instruments and measurement properties. In 41 % of the reviews, compared to 30 % in our previous study, the methodological quality of the included studies was assessed. In 58 %, compared to 55 %, the quality of the included instruments was assessed. In 42 %, compared to 7 %, a data synthesis was performed in which the results from multiple studies on the same instrument were somehow combined.
Conclusion:
Despite a clear improvement in the quality of systematic reviews of outcome measurement instruments in comparison with our previous study in 2007, there is still room for improvement with regard to the search strategy, and especially the quality assessment of the included studies and the included instruments, and the data synthesis.
Sexual dysfunction in women is a common and often distressing problem that has a negative impact on quality of life and medication compliance. The problem is often multifactorial, necessitating a multidisciplinary evaluation and treatment approach that addresses biological, psychological, sociocultural, and relational factors. Criteria for sexual interest/arousal disorder require the presence of at least three specific symptoms lasting for at least six months. Lifelong anorgasmia may suggest the patient is unfamiliar or uncomfortable with self-stimulation or sexual communication with her partner. Delayed or less intense orgasms may be a natural process of aging due to decreased genital blood flow and dulled genital sensations. Genito-pelvic pain/penetration disorder includes fear or anxiety, marked tightening or tensing of the abdominal and pelvic muscles, or actual pain associated with attempts toward vaginal penetration that is persistent or recurrent for at least six months. Treatment depends on the etiology. Estrogen is effective for the treatment of dyspareunia associated with genitourinary syndrome of menopause. Testosterone, with and without concomitant use of estrogen, is associated with improvements in sexual functioning in naturally and surgically menopausal women, although data on long-term risks and benefits are lacking. Bupropion has been shown to improve the adverse sexual effects associated with antidepressant use; however, data are limited. Psychotherapy or sex therapy is useful for management of the psychological, relational, and sociocultural factors impacting a woman's sexual function. Clinicians can address many of these issues in addition to providing education and validating women's sexual health concerns.
The Female Sexual Function Index (FSFI) has been validated for use in many countries. It has been used for clinical and research purposes in Sweden, but the reliability and validity of the Swedish version have never been tested.
The aim of this study was to investigate the psychometric properties of the Swedish version of the FSFI.
After informed consent, 50 women with a diagnosis of hypoactive sexual desire disorder (HSDD) and 58 age-matched healthy volunteers completed the questionnaires.
Reliability was tested by Cronbach's alpha and test-retest by Pearson's correlation, convergent validity by correlation of the FSFI and the Sexual Function Questionnaire (SFQ), divergent validity by correlation of FSFI and the Symptoms Checklist-90-Revised (SCL-90-R), and discriminant validity by Student's t-test and chi-square test to assess differences between women with and without HSDD.
Cronbach's alpha was 0.90-0.96 and test-retest reliability was good (r = 0.86-0.93) for all domains in the whole sample; reliability was low for lubrication and pain in the control group. Correlations between all corresponding domains of the FSFI and the SFQ were high for the whole sample (r = 0.74-0.87) and moderate to high for both the clinical and the control group. There was no correlation between most FSFI domains and the SCL-90-R. Discriminant validity was very good for each of the FSFI domains (P = 0.001, t = 7.05-15.58), although the controls reported relatively low scores on the desire domain. The total FSFI score was 31.37 (standard deviation [SD] 2.66) for the clinical group and 17.47 (SD 5.33) for the controls (P = 0.001, t = 15.99).
The Swedish version of the FSFI can be used as a validated and reliable instrument for assessing sexual function in women with HSDD. Ryding EL and Blom C. Validation of the Swedish version of the Female Sexual Function Index (FSFI) in women with hypoactive sexual desire disorder. J Sex Med **;**:**-**.
© 2014 International Society for Sexual Medicine.
Background: Sexuality constitutes an important part of women’s life. Healthy and proper sexual functioning is one of the signs of physical and mental health. The present study aimed to identify the effect of education on sexual health of women with hypoactive sexual desire disorder.
Methods: In this randomized clinical trial, 80 married women at reproductive age were randomly divided into a control and an education group. These women participated in this study based on self-reporting of having hypoactive sexual desire disorder. After six weekly educational sessions regarding sexual health, percentage of changes in sexual desire was assayed using Hurlbert index of sexual desire. Independent and paired t-test and Chi-square test were used to analyze the data.
Results: After the intervention, a significant difference was found between the two groups regarding the sexual desire score (P<0.001). The results also showed a significant difference within groups in this regard (P<0.001).
Conclusion: According to the results of this study, it seems that educational intervention regarding sexual health was effective for the women with hypoactive sexual desire disorder. Thus, establishing sexual health education units in different health centers is highly necessary. These centers can help couples to promote their sexual knowledge and treat their sexual dysfunctions.
Trial Registration Number: IRCT2012101911032N2
Tribulus terrestris as a herbal remedy has shown beneficial aphrodisiac effects in a number of animal and human experiments. This study was designed as a randomized double-blind placebo-controlled trial to assess the safety and efficacy of Tribulus terrestris in women with hypoactive sexual desire disorder during their fertile years. Sixty seven women with hypoactive sexual desire disorder were randomly assigned to Tribulus terrestris extract (7.5 mg/day) or placebo for 4 weeks. Desire, arousal, lubrication, orgasm, satisfaction, and pain were measured at baseline and after 4 weeks after the end of the treatment by using the Female Sexual Function Index (FSFI). Two groups were compared by repeated measurement ANOVA test.
Thirty women in placebo group and thirty women in drug group completed the study. At the end of the fourth week, patients in the Tribulus terrestris group had experienced significant improvement in their total FSFI (p < 0.001), desire (p < 0.001), arousal (p = 0.037), lubrication (p < 0.001), satisfaction (p < 0.001) and pain (p = 0.041) domains of FSFI. Frequency of side effects was similar between the two groups.
Tribulus terrestris may safely and effectively improve desire in women with hypoactive sexual desire disorder. Further investigation of Tribulus terrestris in women is warranted.
Evaluation of: Burri A, Corina G, Myriam L, Timothy S, Qazi R. A multivariate twin study of female sexual dysfunction. J. Sex. Med. 9, 2671-2681 (2012). This study highlights the complicated nature of female sexual dysfunction (FSD), demonstrating both genetic and environmental factors involved in its etiology. The authors gathered the Female Sexual Function Index scores in a twin population, and examined which dimensions of FSD may be genetically determined or environmentally shared. The results indicate that approximately one-third of the covariance between FSD dimensions was genetic, with one identified loci influencing all phases of the sexual response cycle, whereas the other loci influenced only arousal and orgasm function. They also show that specific types of sexual problems may be related more to nonshared environmental factors. Overall, the results suggest FSD is multifactorial.
This article describes the results of an independent small-scale trial with the centrally acting agent bupropion for female hypoactive sexual desire disorder. The main goals were to gain insight into the intrapsychic and interpersonal barriers to improvement associated with the pharmacological treatment of this common disorder. Eligible subjects entered a 2-week run-in period and a 4-week placebo phase, followed by a 20-week treatment phase. In addition to semi-structured clinical interviews and a set of standardized questionnaires, we used 2 self-developed questionnaires, addressing the period between visits and the week preceding each visit. Participants were 16 women who entered the placebo phase and 10 who completed the medication period. Analyses of pre-post scores and of the questionnaire addressing the time between visits yielded no significant changes. The questionnaire focusing on the week preceding each visit indicated improvements in sexual desire, arousability, and orgasmic ease after Week 8. In the clinical interviews, half of the women reported subjective improvements of sexual desire and arousability that could not be transferred to the sexual relationship as a result of individual and dyadic barriers. Overall, a centrally acting agent such as bupropion may be a viable option for female sexual dysfunction, but it seems mandatory to embed it in a psychotherapeutic approach.
While clinical care is frequently directed at making patients "feel better," patients' reports on their functioning and well-being (patient-reported outcomes [PROs]) are rarely collected in routine clinical practice. The International Society for Quality of Life Research (ISOQOL) has developed a User's Guide for Implementing Patient-Reported Outcomes Assessment in Clinical Practice. This paper summarizes the key issues from the User's Guide.
Using the literature, an ISOQOL team outlined considerations for using PROs in clinical practice; options for designing the intervention; and strengths, weaknesses, and resource requirements associated with each option.
Implementing routine PRO assessment involves a number of methodological and practical decisions, including (1) identifying the goals for collecting PROs in clinical practice, (2) selecting the patients, setting, and timing of assessments, (3) determining which questionnaire(s) to use, (4) choosing a mode for administering and scoring the questionnaire, (5) designing processes for reporting results, (6) identifying aids to facilitate score interpretation, (7) developing strategies for responding to issues identified by the questionnaires, and (8) evaluating the impact of the PRO intervention on the practice.
Integrating PROs in clinical practice has the potential to enhance patient-centered care. The online version of the User's Guide will be updated periodically.
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. J Sex Med 2020;XX:XXX–XXX.
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.
Introduction:
Prior medication treatment for hypoactive sexual desire disorder (HSDD) in women has left about half the subjects without benefit. Lorexys (LOR), a proprietary combination of the stimulating/excitatory dopamine-norepinephrine reuptake inhibitor bupropion (BUP) and the sedating/inhibitory serotonergic agonist-antagonist trazodone (TRZ), was developed as a multifunctional solution for this problem.
Aim:
Test efficacy, safety, and tolerability of LOR in a range of doses in a combined phase IB/IIA study in premenopausal outpatients with HSDD.
Methods:
Otherwise healthy premenopausal women from 25-50 years of age with HSDD were tested in an open-label, active-control, one-way crossover study, with three 4-week treatments of extended-release TRZ and/or sustained-release BUP. Evaluations were made before and after each treatment. A washout of at least a week followed each treatment. The order of treatments was a standard dose of BUP; a subtherapeutic dose of BUP and TRZ (LOR-low); and a threshold-therapeutic dose of BUP and TRZ (LOR-mod). A midpoint interim analysis was planned to consider adapting doses for efficacy or safety.
Main outcome measure:
The primary efficacy measure was the Female Sexual Function Index, Desire domain; the main secondary efficacy measures included the Female Sexual Distress Scale-Revised 13th item, on bother about low desire, and a Patient's Global Impression of Change. The main outcome comparison was the proportions of responders. Safety measures were elicited adverse events, Epworth Sleepiness Scale, Columbia Suicide Severity Rating Scale 6-item SCREEN version, vital signs, electrocardiograms, and standard laboratory tests.
Results:
Interim analysis did not require altering doses. Most evaluable subjects responded to LOR-mod (at the standard thresholds for response based on minimum clinically relevant difference from baseline, 79% on Female Sexual Function Index, Desire domain, 87% on Female Sexual Distress Scale-Revised Item 13, and 79% on Patient's Global Impression of Change; each P < .05 vs BUP). As expected, close to half responded to BUP (38%, 45%, and 52%, respectively). Response to LOR-low was intermediate (not significant vs BUP). Sensitivity analyses to compensate for carryover effects supported the efficacy of LOR-mod. Elicited adverse events showed the expected profile of TRZ, but led to no sedative-type dropouts or worsening on the Epworth Sleepiness Scale.
Clinical implications:
The open-label 1-way crossover design of this phase IB/IIA study limits conclusions, but the consistency of responder analyses showing superiority of LOR-mod dose over control, and the lack of central depressant dropouts, favor further development in double-blind placebo-control trials.
Strength & limitations:
Strengths include large margins of efficacy over control agent, rapid onset of action, and rigorous safety assessment. Limitations are open-label, cross-over design/lack of placebo control and 1-month duration of exposure.
Conclusion:
Moderate-dose LOR was generally well-tolerated and was significantly more effective than BUP (active control). The results seem highly favorable compared to previously tested agents. Pyke RE, Clayton AH. Dose-Finding Study of Lorexys for Hypoactive Sexual Desire Disorder in Premenopausal Women. J Sex Med 2019;XX:XXX-XXX.
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.
Background:
To evaluate the safety of flibanserin in premenopausal and naturally postmenopausal women with hypoactive sexual desire disorder (HSDD) in an open-label extension (OLE) study.
Aim:
To examine the safety and tolerability of flibanserin 100 mg once daily at bedtime in the treatment of premenopausal and naturally postmenopausal women with HSDD in a multicenter 28-week OLE study.
Methods:
Patients entering this study received flibanserin or placebo in the double-blinded, placebo-controlled trials of premenopausal and postmenopausal women and in a pharmacokinetic study of postmenopausal women.
Outcomes:
The primary end point of this OLE study was the incidence of adverse events (AEs). Secondary exploratory efficacy measures included the Female Sexual Distress Scale-Revised (FSDS-R) total score and FSDS-R item 13 (distress owing to low desire) score and the Female Sexual Function Index (FSFI) total score. Because the sponsor terminated the study early at discontinuation of the development of flibanserin, only descriptive statistics were calculated.
Results:
Of the 595 patients receiving study medication, 346 and 249 patients were premenopausal and postmenopausal, respectively. The mean number of days of exposure to flibanserin was 72.8 (SD = 41.6). AEs were reported by 352 patients (59.2%), and most AEs (93.8%) were mild or moderate. The most common AEs (≥5%) were dizziness (9.6%), somnolence (8.6%), insomnia (6.2%), and nausea (5.7%). There were no flibanserin-related serious AEs and no instances of suicidal ideation. The safety profile of flibanserin was similar for premenopausal and postmenopausal women. The FSDS-R total scores and FSDS-R item 13 scores were numerically lower at weeks 4, 12, and 20 than at baseline (decrease in distress owing to low desire) for premenopausal and postmenopausal women. Mean FSFI total scores were numerically higher at weeks 4, 12, and 20 than at baseline, irrespective of menopausal status of the patients.
Clinical implications:
The results of this study support the safety and tolerability of flibanserin for the treatment of HSDD in premenopausal and naturally postmenopausal women.
Strengths and limitations:
Although this open-label study was designed to be 28 weeks long, it was discontinued early by the sponsor, and patients' maximum duration of exposure to flibanserin was 23.9 weeks. The open-label design and lack of a placebo-controlled arm are other study limitations.
Conclusion:
In this open-label study, flibanserin 100 mg once daily at bedtime was generally safe and well tolerated by premenopausal and naturally postmenopausal women with HSDD. Simon JA, Derogatis L, Portman D, et al. Flibanserin for Hypoactive Sexual Desire Disorder: An Open-Label Safety Study. J Sex Med 2018;15:387-395.
Background:
The Female Sexual Function Index-desire subscale is the standard measure for clinical trials of hypoactive sexual desire disorder (HSDD), but lacks items assessing sexually related behaviors and attitudes toward partner. Counting satisfying sexual events is criticized, but sexual behavior remains important. Mean treatment differences cannot define clinical significance; responder and remitter analyses help. We reviewed measures on sexual desire and sexual behavior relevant to HSDD, and how to assess clinical significance.
Methods:
We conducted a literature review of measures of sexual desire comparing expert-proposed criteria for dysfunctional desire, expert-developed scales, and scales from patient input. Commonly recognized symptoms of HSDD were identified. Results of HSDD trials and scale validation studies were evaluated to extract responder and remitter values. The utility of distribution-based measures of responders and remitters was assessed.
Outcomes:
Symptom relevance was evaluated as the proportion of symptom sets that included the item; responder and remitter cut points were determined by distribution-based methods.
Results:
12 Validated rating scales, 5 scales primarily derived from expert recommendations and 7 scales initially from patient input, and 5 sets of diagnostic criteria for conditions like HSDD were compared. Content varied highly between scales despite compliance with U.S. Food and Drug Administration recommendations for patient-reported outcomes. This disunity favors an expert-recommended scale such as the Elements of Desire Questionnaire with each of the common items, plus a measure of frequency of sexual activity, eg, item in the Patient Reported Outcomes Measurement Information System. Registrational drug trials, but not psychological treatment trials, usually give responder/remitter analyses, using dichotomized global impressions or anchor-based definitions. Distribution-based methods are more uniformly applicable to define responder and remitter status.
Conclusions:
The Female Sexual Function Index-desire subscale measures the most relevant element of sexual desire, but it would be meaningful to include 4 or 5 more sexual symptoms as end points: sexual thoughts/fantasies, frequency of sexual activity, receptivity, initiations, and possibly avoidance of sexual situations. The Elements of Desire Questionnaire and a measure of sexual frequency may suffice. Responder and remitter analyses show the clinical relevance of a treatment and enable comparisons across trials. Pyke RE, Clayton AH. Assessment of Sexual Desire for Clinical Trials of Women With Hypoactive Sexual Desire Disorder: Measures, Desire-Related Behavior, and Assessment of Clinical Significance. Sex Med Rev 2017;XX:XXX-XXX.
Background:
The efficacy of on-demand drugs for hypoactive sexual desire disorder (HSDD) or female sexual interest/arousal disorder (FSIAD) should be assessed using a validated instrument that assesses the discrete sexual events during which the on-demand drug is taken.
Aim:
To develop and validate an event log for measuring sexual satisfaction and sexual functioning of discrete sexual events.
Methods:
Psychometric assessment was carried out on data of 10,959 Sexual Event Diaries (SEDs) collected during three clinical trials in a total of 421 women with HSDD. Cognitive debriefing interviews were held with 16 women with HSDD.
Outcomes:
Item scores of the SED at the event level and at the subject level, summarized item scores of women during the baseline establishment and active treatment periods, and score changes in women from baseline establishment to active treatment.
Results:
Several items of the initial 16-item SED items showed weak validity. The 16-item SED was refined to the 11-item SED. The reliability, content, and convergent validity of the 11-item SED were confirmed. For most 11-item SED item scores, the ability to discriminate between known groups was confirmed. Larger mean score changes from the baseline establishment period were found in those with than in those without known benefit from the medication, and Guyatt effect sizes ranged from 0.73 to 1.58, thereby demonstrating the ability to detect change.
Clinical translation:
The SED is a good tool for assessing sexual function during a discrete sexual event and for assessing the sexual function of women over longer periods.
Strengths and limitations:
The validation of the SED was performed on data from nearly 11,000 sexual events, gathered as part of a drug development program for HSDD and FSIAD. This amount of data provides very robust results when related to drug use for HSDD and FSIAD, but caution is advised when generalizing the validity of the SED directly to other areas of research (eg, recreational drug use and sexual risky behaviors), because such data were not used in this validation.
Conclusions:
The 11-item SED is a reliable, valid, and responsive instrument and suitable for use in evaluating the effects of on-demand drugs in women with HSDD or FSIAD. van Nes Y, Bloemers J, van der Heijden PGM, et al. The Sexual Event Diary (SED): Development and Validation of a Standardized Questionnaire for Assessing Female Sexual Functioning During Discrete Sexual Events. J Sex Med 2017;XX:XXX-XXX.
Introduction:
Current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) definitions of sexual dysfunction do not identify all sexual problems experienced clinically by women and are not necessarily applicable for biologic or biopsychosocial management of female sexual dysfunction. A unified nomenclature system enables clinicians, researchers, and regulatory agencies to use the same language and criteria for determining clinical end points, assessing research results, and managing patients.
Aim:
To develop nomenclature with classification systems for female sexual desire, arousal, and orgasm disorders with definitions pertinent to clinicians and researchers from multiple specialties who contribute to the field of sexual medicine.
Methods:
Key national and international opinion leaders diverse in gender, geography, and areas of expertise met for 2 days to discuss and agree to definitions of female sexual desire, arousal, and orgasm disorders and persistent genital arousal disorder. The attendees consisted of 10 psychiatrists and psychologists; 12 health care providers in specialties such as gynecology, internal medicine, and sexual medicine; three basic scientists; and one sexuality educator, representing an array of societies working within the various areas of sexual function and dysfunction.
Main outcome measure:
A unified set of definitions was developed and accepted for use by the International Society for the Study of Women's Sexual Health (ISSWSH) and members of other stakeholder societies participating in the consensus meeting.
Results:
Current DSM-5 definitions, in particular elimination of desire and arousal disorders as separate diagnoses and lack of definitions of other specific disorders, were adapted to create ISSWSH consensus nomenclature for distressing sexual dysfunctions. The ISSWSH definitions include hypoactive sexual desire disorder, female genital arousal disorder, persistent genital arousal disorder, female orgasmic disorder, pleasure dissociative orgasm disorder, and female orgasmic illness syndrome.
Conclusion:
Definitions for female sexual dysfunctions that reflect current science provide useful nomenclature for current and future management of women with sexual disorders and development of new therapies.
Objective:
The objective of this study was to evaluate the efficacy of Tribulus terrestris for the treatment of hypoactive sexual desire disorder in postmenopausal women and evaluate its effect on the serum levels of testosterone.
Methods:
We performed a prospective randomized, double-blinded, placebo-controlled study, during 18 months. A total of 45 healthy sexually active postmenopausal women reporting diminished libido were selected to participate in the study and were randomly assigned to receive 750 mg/d of T terrestris or placebo for 120 days. Randomization was performed using sealed envelopes. All participants answered the Female Sexual Function Index and the Sexual Quotient-female version questionnaires and had their serum levels of prolactin, thyroid-stimulating hormone, total testosterone, and sex hormone-binding globulin measured.
Results:
A total of 36 participants completed the study, because 3 from each group were excluded due to side effects and 3 dropped out due to personal reasons. FSFI questionnaire results demonstrated an improvement in all domains in both groups (P < 0.05) except for lubrication which was improved only in the study group. QS-F results showed a significant improvement in the domains of desire (P < 0.01), arousal/lubrication (P = 0.02), pain (P = 0.02), and anorgasmia (P < 0.01) in women who used T terrestris, whereas no improvement was observed in the placebo group (P > 0.05). Moreover, free and bioavailable testosterone levels showed a significant increase in the T terrestris group (P < 0.05).
Conclusions:
Tribulus terrestris might be a safe alternative for the treatment of hypoactive sexual desire disorder in postmenopausal women, because it was effective in reducing symptoms with few side effects. Its probable mechanism of action involves an increase in the serum levels of free and bioavailable testosterone.
Introduction
Hypoactive Sexual Desire Disorder (HSDD) is defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Revised (DSM-IV-TR) as persistent deficient sexual fantasies and desire for sexual activity that causes marked distress or interpersonal difficulty. In the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), HSDD has been subsumed by Female Sexual Interest/Arousal Disorder. However, decades of research based on DSM-IV-TR HSDD criteria form the foundation of our understanding of the essential symptom of distressing low sexual desire, its epidemiology, clinical management, and treatment.
Aim
This publication reviews the state of knowledge about HSDD.
Methods
A literature search was performed using terms HSDD and female sexual dysfunction (FSD).
Main Outcome Measures
Physicians acknowledge that FSD is common and distressing; however, they infrequently address it, citing low confidence, time constraints, and lack of treatment as barriers.
Results
HSDD is present in 8.9% of women ages 18 to 44, 12.3% ages 45 to 64, and 7.4% over 65. Although low sexual desire increases with age, distress decreases; so prevalence of HSDD remains relatively constant across age. HSDD is associated with lower health-related quality of life; lower general happiness and satisfaction with partners; and more frequent negative emotional states. HSDD is underdetected and undertreated. Less than half of patients with sexual problems seek help from or initiate discussions with physicians. Patients are inhibited by fear of embarrassing physicians and believe that physicians should initiate discussions. The Decreased Sexual Desire Screener, a tool for detecting and diagnosing HSDD, is validated for use in general practice.
Conclusion
Women can benefit from intervention in primary care, behavioral health and sexual medicine settings. Psychotherapeutic and pharmacological interventions aim to enhance sexual excitatory process and decrease inhibitory processes. Flibanserin, the first centrally acting daily medication for HSDD, was recently approved in the US for premenopausal women.
IntroductionHypoactive Sexual Desire Disorder (HSDD) is characterized by low sexual desire that causes marked distress or interpersonal difficulty. AimThe aim of this study was to assess the efficacy and safety of the 5-HT1A agonist/5-HT2A antagonist flibanserin in premenopausal women with HSDD. Methods
This was a randomized, placebo-controlled trial in which premenopausal women with HSDD (mean age: 36.6 years) were treated with flibanserin 100 mg once daily at bedtime (qhs) (n = 542) or placebo (n = 545) for 24 weeks. Main Outcome MeasuresCoprimary end points were the change from baseline to study end in Female Sexual Function Index (FSFI) desire domain score and in number of satisfying sexual events (SSE) over 28 days. Secondary end points included the change from baseline in FSFI total score, Female Sexual Distress Scale-Revised (FSDS-R) total score, and FSDS-R Item 13 score. ResultsCompared with placebo, flibanserin led to increases in mean (standard deviation) SSE of 2.5 (4.6) vs. 1.5 (4.5), mean (standard error [SE]) FSFI desire domain score of 1.0 (0.1) vs. 0.7 (0.1), and mean (SE) FSFI total score of 5.3 (0.3) vs. 3.5 (0.3); and decreases in mean (SE) FSDS-R Item 13 score of −1.0 (0.1) vs. −0.7 (0.1) and mean (SE) FSDS-R total score of −9.4 (0.6) vs. −6.1 (0.6); all P ≤ 0.0001. The most frequently reported adverse events in the flibanserin group were somnolence, dizziness, and nausea, with adverse events leading to discontinuation in 9.6% of women receiving flibanserin vs. 3.7% on placebo. Conclusion
In premenopausal women with HSDD, flibanserin 100 mg qhs resulted in significant improvements in the number of SSE and sexual desire (FSFI desire domain score) vs. placebo. Flibanserin was associated with significant reductions in distress associated with sexual dysfunction (FSDS-R total score) and distress associated with low sexual desire (FSDS-R Item 13) vs. placebo. There were no significant safety concerns associated with the use of flibanserin for 24 weeks. Katz M, DeRogatis LR, Ackerman R, Hedges P, Lesko L, Garcia M, and Sand M. Efficacy of flibanserin in women with Hypoactive Sexual Desire Disorder: Results from the BEGONIA trial. J Sex Med 2013;10:1807–1815.
IntroductionSeveral tools for the assessment of sexuality-related distress are now available. The Female Sexual Distress Scale (FSDS) and its revised version (FSDS-R) are extensively validated and among the most widely used tools to measure sexually related personal distress. AimThe aim of the study was to determine the psychometric properties of the Iranian version of the FSDS-R in a population sample of Iranian women. MethodsA total of 2,400 married and potentially sexually active women were recruited and categorized into three groups including (i) a healthy control group; (ii) a group of women with hypoactive sexual desire disorder (HSDD); and (iii) a group of women suffering from other female sexual dysfunction (FSD). Participants were asked to complete a set of questionnaires including the Iranian version of the Female Sexual Function Index (FSFI-IV), the FSDS-R, and the Hospital Anxiety and Depression Scale. Main Outcome MeasuresSexuality-related distress and FSD as assessed by the Iranian version of the FSDS-R and the FSFI-IV are the main outcome measures. ResultsInternal consistencies and test–retest reliability of the FSDS-R across the three assessments points for the three groups were >0.70. The FSDS-R correlated significantly with anxiety, depression, and the FSFI total score. Significant differences in the FSDS-R scores were found between healthy women, women with HSDD, and women with other types of FSD. Factor analysis of the FSDS-R yielded a single-factor model with an acceptable fit. Conclusions
The Persian version of the FSDS-R is a valid and reliable instrument for the assessment of sexuality-related distress in Iranian women and can be used to screen patients with HSDD. Azimi Nekoo E, Burri A, Ashrafti F, Fridlund B, Koenig HG, Derogatis LR, and Pakpour AH. Psychometric properties of the Iranian version of the Female Sexual Distress Scale-Revised in women. J Sex Med **;**:**–**.
This study aimed to assess the efficacy and safety of flibanserin, a serotonin receptor 1A agonist/serotonin receptor 2A antagonist, in postmenopausal women with hypoactive sexual desire disorder (HSDD).
Naturally postmenopausal women with HSDD received flibanserin 100 mg once daily at bedtime (n = 468) or placebo (n = 481) for 24 weeks. Co-primary endpoints were changes from baseline to week 24 in the number of satisfying sexual events (SSEs) across 28 days and in the Female Sexual Function Index (FSFI) desire domain score. Secondary endpoints included change from baseline in Female Sexual Distress Scale-Revised (FSDS-R) Item 13 score (which assesses distress due to low sexual desire), FSDS-R total score, and FSFI total score. The Patient Benefit Evaluation was asked on treatment discontinuation.
There were significant improvements with flibanserin versus placebo in the mean (SE) changes in the number of SSEs (1.0 [0.1] vs 0.6 [0.1]), FSFI desire domain score (0.7 [0.1] vs 0.4 [0.1]), FSDS-R Item 13 score (-0.8 [0.1] vs -0.6 [0.1]), FSDS-R total score (-8.3 [0.6] vs -6.3 [0.6]), and FSFI total score (4.2 [0.4] vs 2.7 [0.4]; all P < 0.01). More women on flibanserin (37.6%) than women on placebo (28.0%) reported experiencing meaningful benefits from the study medication on treatment discontinuation. The most frequent adverse events associated with flibanserin were dizziness, somnolence, nausea, and headache.
In naturally postmenopausal women with HSDD, flibanserin, compared with placebo, has been associated with improvement in sexual desire, improvement in the number of SSEs, and reduced distress associated with low sexual desire, and is well tolerated.
The concept of sexually related personal distress, central to the diagnosis of all female sexual dysfunction (FSD), is currently a subject of scientific debate. Several psychometric instruments have been used to measure sexually related personal distress in women, including the Female Sexual Distress Scale (FSDS) and its revised version (FSDS-R).
To develop a Polish version of the FSDS-R (PL-FSDS-R).
In total, 210 women aged 18–55 years were included in the study. Seventy-five were diagnosed with hypoactive sexual desire disorder (HSDD), 31 were diagnosed with another FSD, and 104 were control. All subjects completed the PL-FSDS-R at baseline (day 0), day 7, and day 28. Internal consistencies were evaluated by Cronbach's α. Intraclass correlation coefficient was used to assess test–retest reliability. Discriminant validity was assessed by comparing mean scores of the FSD and control groups in a between-groups analysis of variance. Receiver operating characteristic (ROC) analysis was performed to determine optimal cutoff values of the PL-FSDS-R.
To measure the validity and reliability of the PL-FSDS-R and to determine optimal cutoff values.
Mean total PL-FSDS-R score was statistically higher in women with HSDD and other FSD compared to healthy individuals, showing the test had discriminant validity. The frequency of sexual intercourse and quality of relationship with sexual partner but not other sexual behaviors were statistically correlated with the PL-FSDS-R score. ROC analysis confirmed these findings. All domains of the PL-FSDS-R demonstrated satisfactory internal consistencies, with a Cronbach's α-value of >0.70 for the entire sample. Test–retest coefficients were between 0.86–0.92, with the best reliability for a 7-day recall period.
The PL-FSDS-R is a reliable questionnaire with good psychometric and discriminative validity, and can be used to measure sexually related personal distress in Polish women with FSD with a cutoff score of ≥13.
The Decreased Sexual Desire Screener is a brief diagnostic instrument for generalized acquired Hypoactive Sexual Desire Disorder in women. During the screening visit of 2 clinical trials, the authors assessed sensitivity of the Decreased Sexual Desire Screener in premenopausal women presenting with decreased sexual desire. The authors compared diagnoses of generalized acquired Hypoactive Sexual Desire Disorder made by clinicians who were not trained or specialized in the diagnosis of female sexual dysfunction using the Decreased Sexual Desire Screener with diagnoses made by expert clinicians after an extensive diagnostic interview. The sensitivity of the Decreased Sexual Desire Screener was 0.946 in a North American trial and 0.960 in a European trial.
Introduction:
Among other causes, low sexual desire in women may result from dysfunctional activation of sexual inhibition mechanisms during exposure to sex. Administration of sublingual 0.5 mg testosterone (T) increases the sensitivity of the brain to sexual cues, which might amplify sexual inhibitory mechanisms further in women already prone to sexual inhibition. Sexual stimulation might elicit a prefrontal cortex (PFC)-mediated phasic increase in sexual inhibition, in which activity of 5-hydroxytryptamine (5-HT, serotonin) is involved. A single dose of 5-HT receptor agonist (5-HT(1A)ra) might reduce the sexual stimulation induced PFC-mediated sexual inhibition during a short period after administration. Consequently, treatment with a single dose of T+5-HT(1A)ra might enhance sexual responsiveness, particularly in women exhibiting sexual inhibition.
Aim:
To investigate if treatment with a single dosage of T+5-HT(1A)ra will produce improvement in sexual functioning in women with Hypoactive Sexual Desire Disorder (HSDD) as the result of dysfunctional high sexual inhibition.
Methods:
Fifty-four women were divided on the basis of their excitatory or inhibitory responses during T+phosphodiesterase type 5 inhibitor (PDE5i) in low (N = 26) and high inhibitors (N = 28). Physiological and subjective indices of sexual functioning were measured in a participant-controlled ambulatory psychophysiological experiment at home (the first week of each drug treatment). In a bedroom experiment (the subsequent 3 weeks), sexual functioning was evaluated by event, week, and monthly diaries.
Main outcome measures:
Subjective: sexual satisfaction, experienced genital arousal, sexual desire. Physiological: vaginal pulse amplitude.
Results:
Women with high inhibition show a marked improvement in sexual function in response to treatment with T+5-HT ra relative to placebo and relative to T+PDE5i.
Conclusions:
The present study demonstrated that on-demand T+5-HT ra is a potentially promising treatment for women with HSDD, particularly for those women who are prone to sexual inhibition.
Introduction
Hypoactive Sexual Desire Disorder (HSDD) is a common form of Female Sexual Dysfunction characterized by low sexual desire that causes distress or interpersonal difficulty.
Aim
This 52-week open-label extension study aimed to assess the safety and tolerability of flibanserin, a postsynaptic 5-HT1A agonist/5-HT2A antagonist, in women with HSDD.
Methods
Women with HSDD who had completed a trial of flibanserin or flibanserin placebo received flexible-dose flibanserin (50 or 100 mg once daily at bedtime [qhs] or 25 or 50 mg twice daily [bid]) for 52 weeks.
Main Outcome Measures
Primary end points were: proportions of women with somnolence, sedation, fatigue, dizziness, nausea, and vomiting (adverse events [AEs] known to be associated with flibanserin); discontinuations due to AEs; and serious AEs. Secondary end points included change from baseline in Female Sexual Distress Scale-Revised total and Item 13 scores and Female Sexual Function Index (FSFI) total and desire domain score scores. FSFI total scores were used to classify women into FSFI remitters (FSFI score >26.55, indicating no clinical sexual dysfunction) and FSFI non-remitters (FSFI score <26.55).
Results
Of the 1723 women who received flibanserin, 962 (55.8%) completed 12 months’ treatment, and 883 women were exposed to flibanserin 100 mg qhs for ≥180 days. Somnolence, sedation, fatigue, dizziness, nausea, and vomiting were reported by 15.8, 1.6, 7.6, 6.9, 6.3, and 1.4% of participants, respectively. A total of 185 participants (10.7%) discontinued due to AEs. Serious AEs were reported by 1.2% of participants. At study end, 42% of baseline non-remitters had improved their FSFI score to remission level. The proportion of baseline FSFI remitters in remission rose from 83% at week 4 to a stable value of ∼90%.
Conclusion
Flibanserin was well tolerated. Sexual function improved in women who were not FSFI remitters at baseline, and was maintained in those who were remitters at baseline.
Introduction:
Current methods for diagnosing hypoactive sexual desire disorder (HSDD) can be complicated and time-consuming. A previous study reported validity and reliability of a structured diagnostic method created for clinical trials that can be performed in approximately 1 hour.
Methods:
A more succinct tool is needed for incorporation into busy physician practices. Therefore, a brief HSDD screening tool was developed consisting of four self-report questions with an interpretable cut-score and concise confirmatory physician interview.
Main outcome measures:
Accuracy of the HSDD screener cut-score alone, and in combination with physician interview, was then separately evaluated when compared with in-depth interview diagnosis. RESULTS. The results showed good agreement between the two diagnoses (kappa of 0.669 and 0.562 for cut-score alone and cut-score in combination with physician interview, respectively).
Conclusions:
The HSDD screener can reliably detect the likely presence of HSDD in postmenopausal women.
Introduction:
Approximately one out of four sexually active women in the United States uses some form of hormonal contraceptive method because they provide the most effective reversible method of birth control available. However, little attention has been paid to possible adverse effects of combined oral contraceptives (COCs) on sexual functioning.
Aim:
The aim of this study was to examine the potential effects of COCs on women with hypoactive sexual desire disorder (HSDD). It was hypothesized that female patients with generalized, acquired HSDD on COCs have lower androgen levels than those not on COCs.
Methods:
The patients were healthy premenopausal women with HSDD, aged 22-50 years. Subjects had a history of adequate sexual desire, interest, and functioning. Participants were required to be in a stable, monogamous, heterosexual relationship and were screened for any medication or medical or psychiatric disorders that impact desire. The patients met operational criteria for global, acquired HSDD. The 106 patients were divided into two groups: those on COCs (N = 43) and those not on COCs (N = 63). A two-tailed t-test comparison was made between the two groups comparing free and total testosterone and sex hormone-binding globulin (SHBG).
Main outcome measures:
The main outcome measures are the differences between the two groups comparing free testosterone, total testosterone, and SHBG.
Results:
These patients with HSDD on COCs had significantly lower free and total testosterone levels compared with those who were not on COCs. The SHBG was significantly higher in the group on COCs compared with those who were not on COCs.
Conclusion:
The result of this study suggests that COCs in premenopausal women with HSDD are associated with lower androgen levels than those not on COCs. Further research is required to determine if low androgen levels secondary to COCs impact female sexual desire.
Introduction:
Hypoactive sexual desire disorder (HSDD) is the most common sexual complaint in women. Currently there are no validated instruments for specifically assessing HSDD severity, or change in HSDD severity in response to treatment, in premenopausal women. The Sexual Interest and Desire Inventory-Female (SIDI-F) is a clinician-administered instrument that was developed to measure severity and change in response to treatment of HSDD. Seventeen items were included in a preliminary version of the SIDI-F, including 10 items related to desire, and seven items related to possible comorbid factors (e.g., other kinds of sexual dysfunction, general relationship satisfaction, mood, and fatigue).
Aim:
The aim of the study was to use the outcome of item response analyses of blinded data from two randomized, placebo-controlled trials, to assist in the revision of the scale.
Methods:
A nonparametric item response (IRT) model was used to assess the relation between item functioning and HSDD severity on this preliminary version of the SIDI-F.
Results:
Results show that the majority of SIDI-F items demonstrated good sensitivity to differences in overall HSDD severity. That is, there was an orderly relation between differences in option selection for an item and differences in overall HSDD severity. The IRT analyses further indicated that revisions were warranted for a number of these items. Five items were not sensitive to differences in HSDD severity and were removed from the scale.
Conclusion:
The SIDI-F is a brief, clinician-administered rating scale designed to assess severity of HSDD symptoms in women. IRT analyses show that majority of the items of the SIDI-F function well in discriminating individual differences in HSDD severity. A revised 13-item version of the SIDI-F is currently undergoing further validation.
Introduction:
Recently, there has been much discussion in the literature about how to determine the meaningfulness of results generated from a patient-reported outcome measure. A number of reviews have shown that there are two main approaches: anchor- and distribution-based approaches for determining the minimum important difference (MID) for a new measure. There are issues with calculating an MID using each method: Will the two approaches give the same estimate? If the estimates differ, how do you decide on one estimate? Would asking patients directly be more beneficial?
Aim:
A case study was presented to address these issues based on a newly developed diary assessing number of satisfactory sexual events (SSEs) per week in women with hypoactive sexual desire disorder (HSDD).
Methods:
Anchor- and distribution-based estimates were generated from data gathered in two double-blind, placebo-controlled, parallel group trials for the treatment of HSDD (N = 788). A novel interview study was used to ask women directly about an MID for SSEs (N = 77).
Main outcome measures:
Defining the MID for an SSE diary in women with HSDD.
Results:
The estimates varied, producing a range of mean MID estimates between 0.04 and 0.46 SSEs per week.
Conclusion:
We recommend that rather than defining the MID, a range should be selected from the set of estimates formed by the limits of the 95% confidence intervals.
Introduction. The assessment and diagnosis of female sexual dysfunction (FSD) are in a state of transition because of evolving concepts of female sexuality and suggested changes to the FSD diagnostic framework.
Aim. To review the problems with current FSD diagnosis.
Methods. Multidisciplinary experts from five countries were assembled to convene a “Postmenopausal FSD Roundtable on specific topics related to FSD.”
Main Outcome Measure. Expert opinion was based on a review of evidence-based medical literature, presentation, and internal discussion.
Results. Current FSD diagnosis is challenging because of poorly defined distinctions between normal and abnormal, a limited ability to integrate subjective and objective findings and an inability to incorporate contextual factors that play a significant role in sexual behavior. The availability of self-administered questionnaires (SAQs) that assess various domains of female sexual function, as well as those developed specifically for postmenopausal women, suggests that a more structured approach to assessment and diagnosis may be possible. Several SAQs reflecting proposed changes to the FSD diagnostic framework by the American Foundation for Urologic Disease (AFUD), including the Sexual Function Questionnaire (SFQ) and the Female Sexual Distress Scale (FSDS), have been introduced and recently incorporated into a Structured Diagnostic Method (SDM). Recent regulatory decisions and events affecting the development of FSD interventions have highlighted the lack of consensus with regard to clinically meaningful FSD outcomes, as well as shortcomings in a U.S. Food and Drug Administration draft document that provides the primary guidance for conducting FSD clinical studies in the United States.
Conclusions. Given the high cost and inherent risk of clinical studies, continued development efforts toward FSD therapies are unlikely to proceed in the absence of significant changes in regulatory guidance that reflect the current understanding of FSD and incorporate validated assessment tools. Althof SE, Dean J, Derogatis LR, Rosen RC, and Sisson M. Current perspectives on the clinical assessment and diagnosis of female sexual dysfunction and clinical studies of potential therapies: a statement of concern. J Sex Med 2005;2(suppl 3):146–153.
The Sexual Desire Relationship Distress Scale (SDRDS) was developed to address the need for a patient-reported outcome (PRO) measure of sexual distress associated with hypoactive sexual desire disorder (HSDD). The SDRDS is a 17-item PRO that includes items related to personal distress and distress related to relationship with partner.
The aim of this article was to evaluate the psychometric properties of the SDRDS among women with HSDD.
Pre- and post-menopausal women with HSDD or with no sexual dysfunction completed the SDRDS, Sexual Activity Questions, Female Sexual Distress Scale-Revised (FSDS-R), and desire domain of the Female Sexual Function Index (FSFI) at baseline and 2 and 4 weeks later.
The main outcome measures of this article were item performance, internal consistency, test-retest reliability, construct validity, known groups validity, and responsiveness of the SDRDS.
Data from 260 women were analyzed: 101 in each of the pre- and post-menopausal HSDD groups and 29 in each of the pre- and post-menopausal control groups. No differences emerged between pre- and post-menopausal women. Least-squares mean (±standard errors [SE]) SDRDS score was higher in women with HSDD than in women with no sexual dysfunction (43.1 ± 0.9 vs. 6.1 ± 1.7; P < 0.0001), supporting known groups validity. Individual item scores correlated with total scores (r = 0.7-0.9; P < 0.0001). Internal consistency was high, with a Cronbach's alpha of 0.973 at baseline. Test-retest reliability was good, with an intraclass correlation coefficient of 0.89. SDRDS scores correlated strongly with other measures of sexual distress and sexual function including the FSDS-R and FSFI desire domain items. Preliminary analyses suggested that the SDRDS was sensitive to changes in clinical status.
The SDRDS provides a comprehensive and reliable assessment of distress due to decreased sexual desire in women with HSDD and may be a useful measure of treatment effects in clinical trials in women with this condition.
Introduction. The Sexual Function Questionnaire (SFQ) is a self-report outcome measure of female sexual function. It has recently been refined to create a 28-item version (SFQ28) including the addition of a new arousal-cognitive domain.
Aim. This study aimed to validate the SFQ28 in female sexual arousal disorder (FSAD) and hypoactive sexual desire disorder (HSDD) populations and to develop a screening cut-score for the arousal-cognitive domain.
Methods. Women with FSAD (n = 222) and HSDD (n = 114) and 303 women without female sexual dysfunction (FSD) completed the SFQ28, the Female Sexual Distress Scale (FSDS), and the Sexual Quality of Life-Female (SQOL-F) at a clinic visit. Retests were performed within FSD groups only (FSAD: n = 92, HSDD: n = 183), using postal questionnaires 7–14 days later. The optimal cut-score for the arousal-cognitive domain was based on diagnostic tests of sensitivity and specificity from a receiver operating characteristic curve.
Main Outcome Measures. Psychometric analyses.
Results. The factor analysis confirmed the domain structure of the SFQ28. The SFQ28 demonstrated excellent internal consistency, test retest reliability and known groups validity, and good convergent validity with the FSDS and SQOL-F for all domains except pain. The sensitivity/specificity analysis determined a screening cut-score of 5 for the arousal-cognitive domain.
Conclusion. Given the replication of the psychometric data and the cut-scores for each domain, the SFQ28 is a robust measure that can be used in women with either FSAD or HSDD. Symonds T, Abraham L, Bushmakin AG, Williams K, Martin M, and Cappelleri JC. Sexual function questionnaire: Further refinement and validation. J Sex Med **;**:**–**.
Hypoactive sexual desire disorder (HSDD) is the most common form of female sexual dysfunction and is characterized by low sexual desire that causes distress.
The aim of this study was to assess the efficacy and safety of flibanserin, a postsynaptic 5-HT(1A) agonist/5-HT(2A) antagonist, in premenopausal women with HSDD.
North American premenopausal women with HSDD were randomized to 24 weeks' treatment with placebo (N = 295), flibanserin 50 mg (N = 295), or flibanserin 100 mg (N = 290), once daily at bedtime.
Coprimary endpoints were change from baseline to study end in number of satisfying sexual events (SSE) and sexual desire score measured daily using an electronic diary (eDiary). Secondary endpoints included change from baseline to study end in female sexual function index (FSFI) desire domain and total scores, female sexual distress scale-revised (FSDS-R) Item 13 and total scores, and patient's global impression of improvement.
Flibanserin 50 mg and 100 mg led to increases in SSE (P < 0.05 and P < 0.01 vs. placebo, respectively). There was a numerical trend toward improvement in eDiary desire score on flibanserin 100 mg, but statistical significance was not reached (P = 0.07 vs. placebo). FSFI desire domain and total scores increased with both flibanserin regimens (P < 0.05). FSDS-R total and Item 13 scores decreased with flibanserin 100 mg (P < 0.001), indicating reduced sexual distress. More women receiving flibanserin 50 mg and 100 mg considered their HSDD to have improved than women receiving placebo (39.6% and 50.0% vs. 30.3%, respectively) (P < 0.05).
In premenopausal women with HSDD, flibanserin 50 mg and 100 mg once daily at bedtime were well tolerated and associated with statistically significant improvements in SSE, sexual desire (FSFI desire domain score but not eDiary desire score) and overall sexual function, and reduction of sexual distress, vs. placebo.
Hypoactive Sexual Desire Disorder (HSDD) is characterized by low sexual desire that causes marked distress or interpersonal difficulty.
To assess the efficacy and tolerability of flibanserin, a postsynaptic 5-HT1A agonist/5-HT2A antagonist, in the treatment of premenopausal women with HSDD.
North American premenopausal women with HSDD (mean age 35 years) were randomized to 24 weeks' treatment with flibanserin 25 mg twice daily (N=396), 50 mg twice daily (N=392), 100 mg once daily at bedtime (N=395), or placebo (N=398).
Co-primary endpoints were changed from baseline to study end in number of satisfying sexual events (SSE) and sexual desire score, measured daily using an eDiary. Secondary endpoints included change in Female Sexual Distress Scale-Revised (FSDS-R) total score and Item 13 score (distress due to low sexual desire), Female Sexual Function Index (FSFI) total and desire domain scores, and Patient's Global Impression of Improvement.
Flibanserin 100 mg once daily was associated with an increase in SSE (P<0.01 vs. placebo) but the 25 mg and 50 mg twice daily doses were not. No group showed a significant increase in eDiary desire score vs. placebo. All flibanserin regimens improved FSDS-R total, FSDS-R Item 13, FSFI total, and FSFI desire domain scores vs. placebo (P<0.05, for all). More women receiving flibanserin 50 mg twice daily and 100 mg once daily considered their HSDD to have improved than women receiving placebo (44.1% and 47.0% vs. 30.3%, respectively) (P<0.000, 1 vs. placebo). The most frequently reported adverse events in women receiving flibanserin were somnolence (11.8%), dizziness (10.5%), and fatigue (10.3%).
In premenopausal women with HSDD, flibanserin 100 mg once daily was well tolerated and associated with statistically significant improvements in SSE, sexual desire (FSFI desire domain score but not eDiary desire score), sexual function, and decrease in sexual distress vs. placebo.
Flibanserin is a 5-HT(1A) agonist/5-HT(2A) antagonist that has been shown to increase sexual desire and reduce distress in premenopausal women with Hypoactive Sexual Desire Disorder (HSDD).
To assess the efficacy and safety of flibanserin over 24 weeks of double-blind treatment vs. placebo in premenopausal women with HSDD who showed a predefined response after 24 weeks of open-label treatment with flibanserin.
Women (N = 738) were treated with open-label, flexible-dose flibanserin (50 mg or 100 mg/day) for 24 weeks. At week 24, women who showed a predefined response, measured using an eDiary, were randomized to 24 weeks of continued flibanserin therapy at optimized dosage (N = 163) or placebo (N = 170). The criteria for entering the double-blind phase were an increase from baseline to weeks 21-24 of ≥2 satisfying sexual events (SSE) and/or ≥4 "desire days." A "desire day" was one in which a woman reported more than "no" desire.
Coprimary endpoints were change from randomization to study end in SSE and desire score. Secondary measures included change in Female Sexual Function Index (FSFI) total and desire domain scores and Female Sexual Distress Scale-Revised (FSDS-R) total and Item 13 scores.
During the open-label period, mean SSE and desire score approximately doubled, and FSFI, FSDS-R total, and Item 13 scores improved. At the end of the double-blind period, flibanserin was superior to placebo in change from randomization in SSE, desire score, FSFI desire domain and total scores, and FSDS-R total and Item 13 scores (P < 0.05, for all). Flibanserin was well tolerated, and withdrawal reactions were not observed.
At the end of the 24-week randomized withdrawal phase of a 48-week trial in premenopausal women with HSDD, flibanserin was superior to placebo on measures of SSE, sexual desire, overall sexual function, and sexual distress. Flibanserin was well tolerated, and no withdrawal reactions were observed following discontinuation.
Distress associated with low sexual desire is a key feature of hypoactive sexual desire disorder (HSDD). Accurate, reliable, and easy-to-use diagnostic tools to measure such distress are required. The Female Sexual Distress Scale-Revised (FSDS-R) has been shown to have good discriminant validity, test-retest reliability, and internal consistency in measuring sex-related personal distress in women with HSDD. However, the content validity (relevance, clarity, comprehensiveness) of the scale must also be established.
The aim of this study was to assess the content validity of the FSDS-R and to examine the potential of Item 13 as a stand-alone measure of distress associated with decreased sexual desire.
A single-visit content validation study was conducted in three centers in the United States. Women were screened for HSDD; those with HSDD completed the FSDS-R and then underwent debriefing to capture information on their perceptions of the instrument. Participants also rated the relevancy of every FSDS-R item, from 0 ("not at all relevant") to 4 ("extremely relevant").
Female HSDD patients' ratings of the relevance and ease of understanding of the 13 items of the FSDS-R.
Twenty-five women with HSDD were interviewed. Mean relevancy ratings ranged from 1.96 (Item 9) to 3.33 (Item 13). Most participants (76-100%) found every item clear and easy to understand. Item 13 alone demonstrated good content validity, and 56% of participants felt that it covered all of their feelings about their low sexual desire.
This study established the content validity of the FSDS-R and demonstrated that the FSDS-R total score is a relevant endpoint for women with HSDD. The tool's one item specific to low sexual desire (Item 13) was given the highest score and highest relevancy of all items, and over half the sample felt that it covered all of their feelings about their low sexual desire.