Brain activation patterns in women with acquired hypoactive sexual desire disorder and women with normal sexual function: a cross-sectional pilot study.
Ontology highlight
ABSTRACT: Objective
To examine and compare brain activation patterns of premenopausal women with normal sexual function and those with hypoactive sexual desire disorder (HSDD) during viewing of validated sexually explicit film clips.Design
Cross-sectional pilot study.Setting
University-based clinical research center.Patient(s)
Premenopausal women.Intervention(s)
None.Main outcome measure(s)
Areas of brain activation during viewing of sexually explicit film clips.Result(s)
Women with normal sexual function showed significantly greater activation of the right thalamus, left insula, left precentral gyrus, and left parahippocampal gyrus in comparison with women with HSDD, who exhibited greater activation of the right medial frontal gyrus and left precuneus regions.Conclusion(s)
Women with HSDD may have alterations in activation of limbic and cortical structures responsible for acquiring, encoding, and retrieving memory, the processing and memory of emotional reactions, and areas responsible for heightened attention to one's own physical state.
SUBMITTER: Woodard TL
PROVIDER: S-EPMC3828051 | biostudies-literature | 2013 Oct
REPOSITORIES: biostudies-literature
Publications
Brain activation patterns in women with acquired hypoactive sexual desire disorder and women with normal sexual function: a cross-sectional pilot study.
Woodard Terri L TL Nowak Nicole T NT Balon Richard R Tancer Manuel M Diamond Michael P MP
Fertility and sterility 20130702 4
<h4>Objective</h4>To examine and compare brain activation patterns of premenopausal women with normal sexual function and those with hypoactive sexual desire disorder (HSDD) during viewing of validated sexually explicit film clips.<h4>Design</h4>Cross-sectional pilot study.<h4>Setting</h4>University-based clinical research center.<h4>Patient(s)</h4>Premenopausal women.<h4>Intervention(s)</h4>None.<h4>Main outcome measure(s)</h4>Areas of brain activation during viewing of sexually explicit film c ...[more]
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Project description:INTRODUCTION:Female sexual dysfunction affects up to 43% of women in the United States and hypoactive sexual desire disorder (HSDD) is the most common type; however, we lack treatment options showing improvement for this condition. AIMS:To investigate whether acupuncture therapy could improve HSDD. METHODS:Premenopausal women with a primary diagnosis of HSDD were included in a single-arm prospective pilot study that was approved by the institutional review board. After providing informed consent, subjects completed validated questionnaires. Participants underwent 25-minute twice-weekly acupuncture sessions for 5 weeks with one certified acupuncturist. Questionnaires were completed again 6 weeks after onset of treatment. MAIN OUTCOME MEASURES:Based on a statistically significant change in the desire domain of the Female Sexual Function Index from 2.0 (at baseline) to 2.4 (after intervention with a specialist) in our population of patients diagnosed with HSDD, a sample of 13 was determined, with 90% power and ? 0.05. RESULTS:Fifteen women were enrolled and 13 completed the study. Mean age was 36.9 ± 11.4 years. Most were white (n = 9, 60%), heterosexual (n = 15, 100%), and non-smokers (n = 14, 93%). Most were sexually active more than four times per month (n = 8, 53%) and none had a history of sexual abuse (n = 15, 100%). Participants received a mean acupuncture needle application of 17 ± 2 at each session. Sexual function improved after intervention, particularly desire (2.1 ± 0.6 to 3.3 ± 1.2, P < .0001), arousal (P < .0001), lubrication (P = .03), and orgasm (P = .005). CONCLUSION:In this cohort of premenopausal women with HSDD, 5 weeks of acupuncture therapy was associated with significant improvements in sexual function, particularly desire. This supports a role for acupuncture as a therapeutic option for women with low desire.
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Project description: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.
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Project description:BACKGROUNDHypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress and interpersonal difficulty. It is the most prevalent female sexual health problem globally, affecting approximately 10% of women, but has limited treatment options. Melanocortin 4 receptor (MC4R) agonists have emerged as a promising therapy for women with HSDD, through unknown mechanisms. Studying the pathways involved is crucial for our understanding of normal and abnormal sexual behavior.METHODSUsing psychometric, functional neuroimaging, and hormonal analyses, we conducted a randomized, double-blinded, placebo-controlled, crossover clinical study to assess the effects of MC4R agonism compared with placebo on sexual brain processing in 31 premenopausal heterosexual women with HSDD.RESULTSMC4R agonism significantly increased sexual desire for up to 24 hours after administration compared with placebo. During functional neuroimaging, MC4R agonism enhanced cerebellar and supplementary motor area activity and deactivated the secondary somatosensory cortex, specifically in response to visual erotic stimuli, compared with placebo. In addition, MC4R agonism enhanced functional connectivity between the amygdala and the insula during visual erotic stimuli compared with placebo.CONCLUSIONThese data suggest that MC4R agonism enhanced sexual brain processing by reducing self-consciousness, increasing sexual imagery, and sensitizing women with HSDD to erotic stimuli. These findings provide mechanistic insight into the action of MC4R agonism in sexual behavior and are relevant to the ongoing development of HSDD therapies and MC4R agonist development more widely.TRIAL REGISTRATIONClinicalTrials.gov NCT04179734.FUNDINGThis is an investigator-sponsored study funded by AMAG Pharmaceuticals Inc., the Medical Research Council (MRC) (MR/T006242/1), and the National Institute for Health Research (NIHR) (CS-2018-18-ST2-002 and RP-2014-05-001).
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Project description:BackgroundThe 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.MethodsParticipants 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.ResultsAt 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).ConclusionsThe 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 registrationNCT02338960 and NCT02333071 (RECONNECT studies).
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Project description:PurposeData on the role of prolactin (PRL) in the physiologic range in the female sexual response are scanty. We aimed at investigating the association between PRL and sexual function as assessed by the Female Sexual Function Index (FSFI). We explored the presence of a cut-off level of PRL able to identify Hypoactive Sexual Desire Disorder (HSDD).Methods277 pre- and post-menopausal women consulting for Female Sexual Dysfunction (FSD) and sexually active were enrolled in an observational, retrospective study. 42 women were used as no-FSD controls. A clinical, biochemical and psychosexual evaluation was performed. The main outcome measures were: FSFI, Female Sexual Distress Scale-Revised, Middlesex Hospital Questionnaire and Sexual excitation/sexual inhibition scale (SIS/SES).ResultsNormo-PRL FSD women (n = 264) showed lower FSFI Desire score than controls (n = 42), and higher than hyper-PRL FSD women (n = 13). These differences emerged both in pre-menopausal and post-menopausal subjects. In the normo-PRL FSD group, those with PRL in the higher quintile reported higher FSFI Desire scores than those with PRL in the lowest quintile. Women with HSDD presented a lower PRL level than those without (p = 0.032). A ROC curve analysis for PRL showed an accuracy of 0.610 ± 0.044 (p = 0.014) in predicting HSDD. With a threshold of < 9.83 μg/L, sensitivity and specificity for HSDD were 63% and 56%, respectively. Subjects with PRL < 9.83 μg/L also reported lower sexual inhibition (p = 0.006) and lower cortisol levels (p = 0.003) than those with PRL > = 9.83 μg/L.ConclusionsHyper-PRL is associated with low desire; however, among normo-PRL FSD women, those with the lowest levels demonstrated a poorer desire than those with the highest levels. PRL < 9.83 μg/L predicted HSDD and a lower sexual inhibitory trait.
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Project description:Abstract Introduction Hypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress or interpersonal difficulty. It is the most prevalent female sexual health problem worldwide, affecting approximately 1 in 10 women, but has limited treatment options despite its substantial health, social, and economic burden. Melanocortin-4 receptor (MC4R) agonists have emerged as a promising therapy for women with HSDD, although, to date, their mechanism of action is unknown. This study aims to use functional MRI to delineate the reproductive neuroendocrine pathways involved and elucidate how MC4R agonists treat HSDD in women. Methods We conducted a randomized, double-blinded, placebo-controlled, crossover clinical study, using psychometric, functional neuroimaging and hormonal analyses, to assess the effects of MC4R agonism on sexual brain processing in 31 premenopausal women with HSDD. Participants attended on two occasions, receiving either a subcutaneous injection of an MC4R agonist (Bremelanotide 1.75 mg), or placebo, at each study visit, thereby acting as their own controls. Results 31 randomized women were included (mean age 32 years, mean duration of HSDD 41 months). MC4R agonism significantly increased self-reported sexual desire for up to 24-hours post administration, compared to placebo (P=0.007). During functional neuroimaging, MC4R agonism enhanced cerebellar and supplementary motor area activity, as well as deactivating the secondary somatosensory cortex, specifically in response to visual erotic videos, compared to placebo (Z=2.3, P<0.05). In addition, MC4R agonism enhanced functional connectivity between the amygdala-insula and amygdala-thalamus during prolonged visual erotic stimuli, compared to placebo (P=0.025). MC4R agonism resulted in a mean increase in LH of 1.1 iU/L (F [1,58] = 13.38, P=0.0005), and FSH of 0.35 iU/L (F [1,60] = 10.97, P=0.0016) across the 300-minute duration of the study, with no effect observed on circulating estradiol or progesterone levels. Interpretation of results and conclusions:We demonstrate that MC4R agonism deactivates the secondary somatosensory cortex which can reduce the detrimental self-monitoring process often observed in HSDD, thereby increasing sexual desire. Furthermore, cerebellar and supplementary motor area activation by MC4R agonism are associated with increased sexual arousal and sexual motor imagery respectively. Finally, MC4R agonism enhanced functional connectivity between key limbic structures which can be disrupted in HSDD. In summary, these data identify the previously undescribed neural substrates and connections through which MC4R agonism modulates sexual brain processing to increase sexual desire. These findings provide mechanistic insight for the action of MC4R agonism in sexual behaviour and are relevant to ongoing therapeutic development for HSDD and for MC4R agonist development more widely. Trial registration: ClinicalTrials.gov identifier NCT04179734.Funding: Investigator-sponsored study funded by AMAG Pharmaceuticals Inc, MRC and NIHR. Presentation: Saturday, June 11, 2022 1:00 p.m. - 1:05 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
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Project description:Sexuality is a basic human need, which is expressed in the context of intimate personal relations. However, in studies of women's sexuality, men's attitudes are often overlooked. Health care providers can benefit from the examination of how both women and men perceive women's sexual desire and what are the most acceptable avenues for treatment for women's hypoactive sexual desire disorder (HSDD). This research aimed to explore differences between women and men on the factors affecting women's sexual desire and the appropriate avenues for treatment. Data were collected using an online questionnaire from 233 heterosexual adults who had a dyadic, steady intimate relationship over most of the previous year. A theory-based questionnaire of 28 items was developed to explore the factors associated with women's sexual desire. One quarter (7/28) of the items affecting women's sexual desire were ranked significantly differently between women and men. Among women, interpersonal issues and physical attraction, and among men, physical attraction and daily hassles were the significant predictors of women's sexual desire. Women more than men endorsed psychological help such as a sex therapist or psychologist as a more appropriate treatment for HSDD, while both men and women viewed the internet as a reasonable way to gain treatment information. Both women and men viewed gynecologists as a more acceptable source of treatment than a family doctor. Religious authorities were the least likely source of treatment advice for both women and men. The results support a multi-dimensional model of women's sexual desire and suggest that psychological interventions to treat HSDD may be preferred by women more than men.
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Project description:ImportanceDespite being the most common female sexual health complaint worldwide, current treatment options for hypoactive sexual desire disorder (HSDD) are limited in their safety and effectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonal axis with additional emerging roles in sexual and emotional behavior; however, its effects in women with HSDD are unknown.ObjectiveTo test the hypothesis that kisspeptin enhances sexual and attraction brain processing in women with HSDD.Design, setting, and participantsThis randomized clinical trial was double-masked and placebo controlled with a 2-way crossover. The trial was conducted in a university research setting in the UK from October 2020 to April 2021. Eligible participants were premenopausal women with HSDD. Functional neuroimaging, psychometric, and hormonal analyses were employed to investigate the effects of kisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facial attraction (face images of varying attractiveness). Data were analyzed from May to December 2021.InterventionsA 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion.Main outcomes and measuresBlood oxygen level-dependent responses across the whole brain and regions of interest during kisspeptin vs placebo administration in response to erotic and facial attraction stimuli.ResultsOf the 40 participants who were randomized, 32 women completed both kisspeptin and placebo visits, with a mean (SE) age of 29.2 (1.2) years. Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P < .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02). Furthermore, positive correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic videos, and baseline distress relating to sexual function (r = 0.469; P = .007). Kisspeptin's enhancement of posterior cingulate cortex activity in response to attractive male faces also correlated with reduced sexual aversion, providing additional functional significance (r = 0.476, P = .005). Kisspeptin was well-tolerated with no reported adverse effects.Conclusions and relevanceThese findings lay the foundations for clinical applications for kisspeptin in women with HSDD.Trial registrationISRCTN trial registry identifier: ISRCTN17271094.
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Project description:IntroductionCounts of satisfying sexual events (SSEs) per month have been criticized as an end point in treatment trials of women with hypoactive sexual desire disorder (HSDD) but grounding improvement in sexual desire by assessing changes in sexual behavior remains of some importance.MethodsWe conducted a literature review to find validated measurements that are specific sexual behavioral correlates of low sexual desire. We compared expert-proposed criteria for dysfunctional desire, expert-developed sets of scale items, and self-rated scales developed before issuance of, or in accordance with, the Food and Drug Administration's guidance on developing patient-reported outcomes. Behavioral measurements of HSDD were isolated from these sets of criteria or scales.Main outcome measuresWe outline a plan to evaluate such behavioral measurements of HSDD with reference to SSEs.ResultsEleven rating scales, four expert-originated and seven self-rated scales mainly derived from patient input were identified as well validated and relevant to HSDD. Three recent sets of diagnostic criteria for conditions such as HSDD were compared with the scales. Twenty-four different symptoms were found in the scales. Content found relevant to HSDD during development of the rating scales varied highly among measurements, including the self-rated scales developed in conformity with current recommendations for patient-reported outcome measurements. The only item on all sets was desire for sexual activity. Four other items were in approximately at least half the sets: sexual thoughts or fantasies, frequency of sexual activity, receptivity, and initiations. Sexual thoughts or fantasies were in every expert-derived set but in only three of the seven patient-derived sets. Receptivity was in five of the seven expert-derived sets vs two of the seven patient-derived sets. Frequency of sexual activity was in one of the seven expert-derived sets but in five of the patient-derived sets. Initiation was in approximately half the two sets. All other items were on one to three sets each. We identified three sexual behaviors of validated specificity for female HSDD: frequency of sexual activity, receptivity, and initiations. Six or seven items are relevant and informative. The item on frequency of sexual activity in the Changes in Sexual Functioning-Female scale is the only item that covers frequency of dyadic and solitary sexual activity. An item in the Female Sexual Desire Questionnaire (FSDQ) covers the intuitively relevant topic of frequency of sexual activity motivated by the woman's desire. Three FSDQ items on initiations and two items on receptivity reflect expert opinion on the sexual behaviors of most relevance to HSDD, but the FSDQ has not been validated in women with HSDD.ConclusionsSSEs have been discredited as the primary measurement in clinical trials of women with HSDD, but it would be meaningful to include at least one sexual behavioral symptom specific to HSDD as an end point. Expert-recommended sexual behaviors specifically related to HSDD are irregularly represented in self-rating scales whether developed as in the Food and Drug Administration guidance on patient-reported outcomes or not. Six or seven items on sexual behavior in self-rated scales can be recommended for relevance to women with HSDD in clinical trials. Items on female sexual behavior should be tested in comparison with SSEs in women with HSDD for relevance and for treatment sensitivity, and responder and functional and dysfunctional cutoffs should be determined before incorporation into large-scale clinical trials. Pyke R and Clayton A. What Sexual Behaviors Relate to Decreased Sexual Desire in Women? A Review and Proposal for End Points in Treatment Trials for Hypoactive Sexual Desire Disorder. Sex Med 2017;5:e73-e83.
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Project description:ObjectiveTo evaluate the long-term safety and efficacy of bremelanotide as treatment for hypoactive sexual desire disorder in premenopausal women.MethodsWomen 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.ResultsThe 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.ConclusionDuring 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 registrationClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302).Funding sourcePalatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.
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