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Endocrine Abstracts (2022) 81 P445 | DOI: 10.1530/endoabs.81.P445

1Imperial College London, Endocrinology and Investigative Medicine, London, United Kingdom; 2Invicro, London, United Kingdom; 3Imperial College Healthcare NHS Trust, Sexual Medicine, London, United Kingdom; 4Imperial College Healthcare NHS Trust, Endocrinology, London, United Kingdom

Introduction: Sexual desire is a key component of the sexual response model. Absence or deficiency of sexual desire can lead to marked distress or interpersonal difficulty, termed ‘hypoactive sexual desire disorder’ (HSDD). HSDD is the most common female sexual health complaint worldwide, affecting up to 10% of women. Despite its detrimental impact on psychological well-being and quality of life, treatment options are currently limited. The hormone kisspeptin is a key endogenous activator of the hypothalamic-pituitary-gonadal axis, with emerging roles in sexual and emotional behaviour, and thus could serve as a novel treatment option in women with HSDD.

Methods: We performed a randomized, double-blind, two-way crossover, placebo-controlled study in 32 premenopausal women with HSDD. We used psychometric, functional neuroimaging, and hormonal analyses to investigate the effects of kisspeptin administration on brain activity, in response to erotic stimuli (erotic videos) and facial attraction (images of faces of varying attractiveness).

Results: Kisspeptin administration resulted in an increase in self-reported ratings of feeling ‘sexy’, compared to placebo, measured using the Sexual Arousal and Desire Inventory (t[32]=2.27, P=0.03). On functional MRI, kisspeptin administration deactivated the left inferior frontal gyrus and activated the postcentral and supramarginal gyrus in response to erotic videos (Z=2.3, P<0.05). Kisspeptin administration deactivated the secondary somatosensory cortex (Z=2.3, P<0.05) and enhanced activation in the posterior cingulate cortex on viewing male faces, which correlated with a reduction in self-reported sexual aversion (r=0.476, P=0.005). Kisspeptin resulted in a mean increase in LH of 2.75 iU/l (F(1, 62)=6.084, P=0.02) and FSH of 0.37 iU/l (F(1, 62)=4.030, P=0.05) across the 75-minute duration of the study as expected, with no effect observed on downstream circulating estradiol, progesterone or testosterone levels.

Discussion: Our results demonstrate that kisspeptin administration to women with HSDD increases their self-reported ratings of feeling ‘sexy’. Our brain activity changes provide mechanistic insight for this, with deactivation of the left inferior frontal gyrus, likely serving to reduce internal monologue and response inhibition. Furthermore, kisspeptin’s deactivation of the secondary somatosensory cortex can reduce a woman’s focus on herself, her body image, and related negative thoughts, thus augmenting her judgement of male facial attractiveness. Finally, kisspeptin’s actions in the posterior cingulate cortex can serve to increase feelings of romantic love and reward processing, thereby reducing sexual aversion and increasing sexual desire. These behavioural and mechanistic findings in women with HSDD lay the foundations for clinical applications for kisspeptin in psychosexual disorders.

Volume 81

European Congress of Endocrinology 2022

Milan, Italy
21 May 2022 - 24 May 2022

European Society of Endocrinology 

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