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A network analysis of female sexual function: comparing symptom networks in women with decreased, increased, and stable sexual desire.

ABSTRACT: Problems related to low sexual desire in women are common clinical complaints, and the aetiology is poorly understood. We investigated predictors of change in levels of sexual desire using a novel network approach, which assumes that mental disorders arise from direct interactions between symptoms. Using population-based data from 1,449 Finnish women, we compared between-subject networks of women whose sexual desire decreased, increased, or remained stable over time. Networks were estimated and analyzed at T1 (2006) and replicated at T2 (2013) using R. Domains included were, among others, sexual functions, sexual distress, anxiety, depression, body dissatisfaction, and relationship status. Overall, networks were fairly similar across groups. Sexual arousal, satisfaction, and relationship status were the most central variables, implying that they might play prominent roles in female sexual function; sexual distress mediated between general distress and sexual function; and sexual desire and arousal showed different patterns of relationships, suggesting that they represent unique sexual function aspects. Potential group-differences suggested that sex-related pain and body dissatisfaction might play roles in precipitating decreases of sexual desire. The general network structure and similarities between groups replicated well; however, the potential group-differences did not replicate. Our study sets the stage for future clinical and longitudinal network modelling of female sexual function.

SUBMITTER: Gunst A

PROVIDER: S-EPMC6202312 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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A network analysis of female sexual function: comparing symptom networks in women with decreased, increased, and stable sexual desire.

Gunst Annika A Werner Marlene M Waldorp Lourens J LJ Laan Ellen T M ETM Källström Marianne M Jern Patrick P

Scientific reports 20181025 1

Problems related to low sexual desire in women are common clinical complaints, and the aetiology is poorly understood. We investigated predictors of change in levels of sexual desire using a novel network approach, which assumes that mental disorders arise from direct interactions between symptoms. Using population-based data from 1,449 Finnish women, we compared between-subject networks of women whose sexual desire decreased, increased, or remained stable over time. Networks were estimated and ...[more]

PMID: 30361518

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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.

Project description:BackgroundFor the treatment of female sexual dysfunction, the most relevant outcome measures are patient-reported treatment effects and changes in symptoms, underscoring the need for reliable, validated patient-reported outcome (PRO) instruments. The aim of this study was to evaluate the psychometric characteristics (validity and reliability) of the Female Sexual Distress Scale-Desire/Arousal/Orgasm (FSDS-DAO) PRO measure, which was adapted from the validated FSDS-Revised (FSDS-R) questionnaire and added 2 questions involving arousal and orgasm.MethodsPsychometric analyses were based on the data from a multicenter phase 2b dose-finding study that compared the safety and efficacy of bremelanotide versus placebo and were conducted in the evaluable modified intent-to-treat population (N = 325) from that study. Psychometric evaluation of the new items in the FSDS-DAO included confirmatory factor analyses, tests of internal consistency and test-retest reliability, examinations of convergent and discriminant validity, and determination of responsiveness. The validity of the FSDS-DAO was evaluated based on previously developed instruments, including the Female Sexual Function Index (FSFI), General Assessment Questionnaire (GAQ), Women's Inventory of Treatment Satisfaction (WITS-9), and Female Sexual Encounter Profile-Revised (FSEP-R).ResultsConfirmatory factor analyses demonstrated that the FSDS-DAO items fit very well (Bentler's comparative fit index of 0.929). Cronbach's α for the FSDS-DAO total score was ≥ 0.91 at Visits 1, 2, 5, and 12, demonstrating adequate internal consistency reliability. Test-retest reliability was acceptable with an intra-class coefficient of 0.61 and a Spearman's correlation coefficient score of 0.62 between Visits 1 and 2 (4 weeks). Acceptable construct validity was demonstrated by significant correlations with related PRO scales in the expected directions and magnitude. For example, participants reporting the worst levels of sexual function on the FSFI also showed the worst FSDS-DAO scores at Visits 5 and 12. The FSDS-DAO total score was responsive to change.ConclusionsEvidence supports the validity and reliability of the FSDS-DAO for assessing sexually related distress in women with female sexual arousal disorder and/or hypoactive sexual desire disorder; the addition of the arousal and orgasm items did not impact the validity and reliability of the measure. Clinical Trial Registration ClinicalTrials.gov NCT01382719.

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).

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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A network analysis of female sexual function: comparing symptom networks in women with decreased, increased, and stable sexual desire.

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A network analysis of female sexual function: comparing symptom networks in women with decreased, increased, and stable sexual desire.

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