Effects of Kisspeptin Administration in Postmenopausal Women with Low Sexual Desire
Lead Research Organisation:
Imperial College London
Department Name: Metabolism, Digestion and Reproduction
Abstract
Context: Menopausal symptoms have a marked impact on women's lives with approximately 50% suffering from low sexual desire (LSD) with a large proportion distressed by this and seeking medical help. Indeed, the WHO strongly recognises the crucial positive influences of fulfilling sexual experiences on well-being throughout life. In the UK, menopause has been placed at the forefront of the healthcare agenda by the Department of Health following its publication of the Women's Health Strategy in 2022. This identified research into menopause treatments and psychosexual wellbeing as a key priority. Collectively, this aligns with priority 5.1 of the UKRI Strategy: 'Securing better health, ageing and wellbeing'.
Challenge: Despite the high global health and social burden of menopausal LSD, the available therapeutic approaches are unsatisfactory due to their very limited efficacy and side-effect profiles. Crucially, a significant number of women suffer with persistent LSD despite first-line hormone replacement therapy (HRT), which only consistently improves pain during sex, but not sexual desire and arousal. Taken together, there is a significant unmet need to identify novel, safer, and more effective treatments to address the considerable burden of LSD in postmenopausal women.
Kisspeptin and our pilot data: We have recently shown that administration of the reproductive neuropeptide kisspeptin to men and premenopausal women with LSD robustly modulates sexual brain processing with associated improvements in sexual desire/arousal (independent of downstream sex-steroids). To explore the potential benefit of kisspeptin in postmenopausal women with LSD (despite HRT) and provide mechanistic insight, we have undertaken an in vivo pilot study in ovariectomised (OVX) female mice with oestradiol (E2) replacement (as a rodent model to mimic the postmenopausal state on HRT treatment). This demonstrated that whereas E2 alone does not restore sexual motivation (akin to human sexual desire) in OVX mice, the addition of kisspeptin fully restored sexual motivation. Collectively, this pilot data in animals and our previous clinical findings suggests that kisspeptin administration may augment sexual behaviour in postmenopausal women with LSD and so serves as the timely research theme for this application.
Challenge: Despite the high global health and social burden of menopausal LSD, the available therapeutic approaches are unsatisfactory due to their very limited efficacy and side-effect profiles. Crucially, a significant number of women suffer with persistent LSD despite first-line hormone replacement therapy (HRT), which only consistently improves pain during sex, but not sexual desire and arousal. Taken together, there is a significant unmet need to identify novel, safer, and more effective treatments to address the considerable burden of LSD in postmenopausal women.
Kisspeptin and our pilot data: We have recently shown that administration of the reproductive neuropeptide kisspeptin to men and premenopausal women with LSD robustly modulates sexual brain processing with associated improvements in sexual desire/arousal (independent of downstream sex-steroids). To explore the potential benefit of kisspeptin in postmenopausal women with LSD (despite HRT) and provide mechanistic insight, we have undertaken an in vivo pilot study in ovariectomised (OVX) female mice with oestradiol (E2) replacement (as a rodent model to mimic the postmenopausal state on HRT treatment). This demonstrated that whereas E2 alone does not restore sexual motivation (akin to human sexual desire) in OVX mice, the addition of kisspeptin fully restored sexual motivation. Collectively, this pilot data in animals and our previous clinical findings suggests that kisspeptin administration may augment sexual behaviour in postmenopausal women with LSD and so serves as the timely research theme for this application.
