Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder

Abstract

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

Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder

“…Therefore, circulating kisspeptin levels were stable during the fMRI and intrainfusion psychometric assessments. In parallel, kisspeptin significantly increased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to similar levels reported using this administration protocol, confirming bioactivity (eFigure 2A and B in Supplement 2). No changes in downstream testosterone or cortisol (eFigure 2C and D in Supplement 2) were observed during the 75-minute study period, in keeping with previous work …”

“…Pearson correlation was used to assess correlations between brain activity in a priori-defined ROIs with behavioral measures, in keeping with our and others' previous work. 21,24,25,27,30,31 To adjust for the number of analyses, a reduced α threshold from standard P < .05 to P < .01 identified statistical significance in the correlation analyses, in line with previous work. 21…”

“…Using these data, with an α of .05, power of 0.8, and assuming correlation between means of 0.40, a power calculation was performed, resulting in a sample size of 31. Our final sample size of 32 participants also compares favorably with our previous studies examining the effects of kisspeptin on fMRI brain activity in healthy men and women with HSDD as well as empirically derived estimates of optimal sample sizes in fMRI studies . To allow for dropouts and exclusions, 37 participants were recruited.…”

“…Differences between baseline and change in psychometric scores during kisspeptin administration compared with placebo were analyzed using paired 2-tailed t tests. Pearson correlation was used to assess correlations between brain activity in a priori–defined ROIs with behavioral measures, in keeping with our and others’ previous work . To adjust for the number of analyses, a reduced α threshold from standard P < .05 to P < .01 identified statistical significance in the correlation analyses, in line with previous work …”

Multiband acquisition sequences for fMRI: Proceed with caution

“…Our results and the sequence we implemented were broadly in accordance with others who have documented similar testing data. 6,28,33 This sequence has been successfully deployed in a number of projects [34][35][36][37][38][39][40][41] but we have also modified it on occasion to suit particular studies, for example using thinner 2 mm slices to reduce susceptibility artefacts in ventral brain regions. 42,43 My intention here is not to advocate for the use of this particular set of sequence parameters, or any other set, but to recommend that individual researchers think carefully about their use of multiband and do appropriate testing and development work.…”