Endocrine Abstracts

Successful reproduction in humans at a population level, is reliant on the careful co-ordination of reproductive hormones with associated behaviours. Kisspeptin is a neuropeptide that is critical for normal hypothalamic function of the reproductive hormonal axis. However beyond its hormonal effects, non-human data suggests an emerging role for kisspeptin in a range of animal behaviours through extra-hypothalamic downstream neuroendocrine pathways. Until recently, the roles of kisspeptin in human behaviour were unknown. Investigating this through a multi-method approach employing behavioural, neuroimaging and hormonal analyses has revealed several novel neuroendocrine actions of kisspeptin in human behaviour, ultimately with clinical potential. We have shown that kisspeptin administration to healthy men enhances limbic brain activity (the main behavioural system), specifically in response to sexual stimuli. Furthermore, these changes in brain activity correlate with associated behavioural parameters such as reward, mood, and sexual aversion, providing key functional significance. In addition, attraction is a key initiator of sexual behaviour in humans and so was examined in a further study. Here, kisspeptin increases brain activity specifically in ‘attraction and beauty centres’ in direct response to olfactory and visual attraction cues. The next step in this series of studies was to translate these findings into patients for the first time. Hypoactive Sexual Desire Disorder (HSDD) is characterised by a deficiency of sexual desire with marked distress and affects up to 10% of men and women. Current treatment options are limited in safety and effectiveness. Kisspeptin administration to men with HSDD (n=32) potently increases penile tumescence (by 56%,P=0.002) and sexual desire (P=0.02), through modulations of sexual brain processing. In women with HSDD (n=32), kisspeptin administration increases self-reported ratings of feeling ‘sexy’ (P=0.03), with associated sexual brain processing changes. Collectively, these studies lay the foundation for future clinical applications of kisspeptin in patients with psychosexual disorders.