Importance: The absence or deficiency of sexual desire leading to distress or interpersonal difficulty
defines ‘hypoactive sexual desire disorder’ (HSDD). Despite being the most common female sexual
health complaint worldwide, current treatment options for 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.
Objective: To test the hypothesis that kisspeptin enhances sexual and attraction brain processing in
women with HSDD.
Design: A randomized, double-blind, two-way crossover, placebo-controlled clinical trial. 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).
Setting: The trial was conducted in a university research setting from October 2020 to April 2021. Data
were analyzed from May to December 2021.
Participants: 32 premenopausal women with HSDD for at least 6 months’ duration.
Interventions: 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate
placebo infusion.
Main Outcome and Measures: Blood 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.
Results: Of the 40 participants who were randomized, 32 women completed both kisspeptin and
placebo visits, and the mean (SEM) age was 29.2 (1.2) years. Kisspeptin administration resulted in
modulations in sexual and facial attraction brain processing (all P<.05). Furthermore, positive
correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic
videos, and baseline distress relating to sexual function (P<.01). In addition, kisspeptin’s enhancement
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of posterior cingulate cortex activity in response to attractive male faces correlated with reduced
sexual aversion (P<.01), providing additional functional significance. Kisspeptin was well-tolerated
with no reported side-effects.
Conclusions and Relevance: These findings lay the foundations for clinical applications for kisspeptin
in women with HSDD.
Trial Registration: ISRCTN Trial Registry: ISRCTN17271094.