Investigating the effects of kisspeptin administration on sexual brain processing in women and men with Hypoactive Sexual Desire Disorder (HSDD)

Abstract

Background Hypoactive sexual desire disorder (HSDD) refers to a loss of desire for sexual activity causing marked distress. The disorder affects up to 10% of women and 8% of men, making it among the most common sexual health complaints. Kisspeptin is an endogenous neuropeptide which plays a vital role in the downstream signalling of reproductive hormones. Kisspeptin receptors are expressed primarily in the hypothalamus but also in limbic regions, suggesting kisspeptin may play a role in behaviour as well as reproduction.

Aims To investigate the effects of kisspeptin on sexual brain processing using fMRI in women and men with HSDD.

Method Two randomised, cross-over, double-blinded placebo-controlled studies were conducted with 32 women and 32 men with HSDD. Both studies followed the same protocol. Sexual brain processing was assessed using a ‘short video’ block design task, a ‘long video’ naturalistic design task and a ‘facial attractiveness’ event-related design task. Hormonal and psychometric questionnaire data were also collected. In the male study, an additional penile tumescence measure was used to assess objective sexual arousal during the long video task.

Results In both male and female participants kisspeptin deactivated brain regions which are thought to be hyperactive in HSDD in response to visual sexual stimuli. Brain data correlated with changes in psychometric scores, providing behavioural relevance, and in the male participants, kisspeptin significantly enhanced the penile tumescent response.

Conclusions The pathology of HSDD may be related to hyperactivity in cortical brain regions which are associated with introspective self-monitoring, leading to a top-down inhibition of the sexual response. Kisspeptin may act to deactivate these brains regions, thereby blocking this ‘top-down’ effect. These proof-of-concept studies suggest further research of kisspeptin analogues may provide a useful treatment for HSDD in both sexes.