The hormone kisspeptin could possibly be used to treat men and women distressed by their low sexual desire, in accordance with two recent studies.

The studies, each published in JAMA Network Open, found that giving kisspeptin can boost sexual responses in men and women who’ve hypoactive sexual desire disorder (HSDD) – a condition characterised by low sexual desire that’s distressing to the person. HSDD affects up 10 percent of girls and eight percent of men worldwide and might have devastating psychological and social impacts.

The studies were led by clinicians and scientists at Imperial College London and Imperial College Healthcare NHS Trust. They were funded by the National Institute for Health and Care Research (NIHR) Imperial Biomedical Research Centre (NIHR-Imperial BRC) and the Medical Research Council, a part of UK Research and Innovation.

Kisspeptin is a naturally-occurring hormone that stimulates the discharge of other reproductive hormones contained in the body. The team have previously shown in men with intact sexual desire that kisspeptin can enhance responses to sexual stimuli, and boost attraction brain pathways, independent of other reproductive hormones like testosterone. Now, they investigated the consequences in men and women with low sexual desire for the primary time.

These two clinical trials involved 32 pre-menopausal women and 32 men with HSDD. In each studies, patients underwent scanning of the brain using MRI, in addition to blood and behavioral tests. Kisspeptin administration improved sexual brain processing in each men and women, leading to positive effects on sexual behavior in comparison with placebo. These are the primary clinical studies to explore the power of kisspeptin to spice up sexual pathways in men and women distressed by their low sexual desire.

Kisspeptin-based treatments

The researchers imagine that the outcomes lay the foundations for kisspeptin-based treatments for men and women with HSDD.

Dr Alexander Comninos, from the Department of Metabolism, Digestion and Reproduction at Imperial College London, Consultant Endocrinologist at Imperial College Healthcare NHS Trust and co-senior writer of the study, said:

“Low sexual desire will be distressing and so end in HSDD. This may have a serious detrimental impact on relationships, mental health, and fertility. Regardless that it is comparatively common, treatment options in women are limited, carry significant side-effects and in some cases will be harmful to even try. And unfortunately, these treatments have limited effectiveness. In men there are currently no licensed treatments and none on the horizon. Due to this fact, there’s an actual unmet need to seek out recent, safer and simpler therapies for this distressing condition for each men and women looking for treatment.

“Our two studies provide proof-of-concept for the event of kisspeptin treatments, as we offer the primary evidence that kisspeptin is a potentially protected and effective therapy for each men and women with distressing low sexual desire. Moreover in men, we show that kisspeptin can have positive effects not only within the brain but in addition within the penis by increasing rigidity. Moreover, kisspeptin was well-tolerated by each men and women with no side-effects reported, which is crucial from a drug development standpoint. We now plan to take things forward to hopefully realize the potential of kisspeptin therapeutics in psychosexual disorders – sexual problems that are psychological in origin, similar to unexplained low libido.”

Next steps

Professor Waljit Dhillo, an NIHR Senior Investigator, also from the Department of Metabolism, Digestion and Reproduction at Imperial College London, Consultant Endocrinologist at Imperial College Healthcare NHS Trust and co-senior writer of the study, added:

“Our studies construct on our previous work to evaluate the effectiveness of kisspeptin and its boosting effects when it comes to arousal and attraction. It is extremely encouraging to see the identical boosting effect in each men and women, although the precise brain pathways were barely different as may be expected.

“Collectively, the outcomes suggest that kisspeptin may offer a protected and much-needed treatment for HSDD that affects hundreds of thousands of individuals around the globe and we stay up for taking this forward in future larger studies and in other patient groups.”

Boosting effect

The study in women involved a randomized, double-blind, two-way crossover, placebo-controlled trial at Invicro and Hammersmith Hospital (a part of Imperial College Healthcare NHS Trust), between October 2020 and April 2021. Data evaluation was carried out by Imperial College London researchers.

32 pre-menopausal heterosexual women with HSDD (aged 19-48 years) accomplished two study visits, one for administration of kisspeptin and one other visit for placebo. Participants accomplished psychometric questionnaires before and towards the tip of kisspeptin or placebo administration to evaluate their mood and behavior. During kisspeptin or placebo administration, participants underwent functional MRI while watching erotic videos and viewing male faces to see how brain activity was affected. Non-erotic exercise videos were used as a control.

The team found that kisspeptin improved sexual and attraction brain activity in key brain areas in women. Additionally they found that ladies who were more distressed by their sexual function showed greater kisspeptin-enhanced brain activity within the hippocampus (a key structure implicated in female sexual desire). Moreover, the more kisspeptin activated the posterior cingulate cortex – a key behavioral brain area – in response to attractive male faces, the less sexual aversion was reported by participants. Crucially, the psychometric analyses revealed that the ladies reported feeling ‘more sexy’ during kisspeptin, in comparison with placebo.

Improved sexual desire

Within the second study, which was also a randomized, double-blind, two-way crossover trial, 32 heterosexual men with HSDD (aged 21-52 years) underwent an identical study with the addition of the measurement of penile rigidity, between January and September 2021.

The study demonstrated that kisspeptin significantly boosted brain activity in key structures of the sexual brain network while also increasing penile rigidity by as much as 56 per cent in comparison with placebo, while viewing an erotic video. Similarly to the study in women, kisspeptin also had greater effects in key brain regions in men more distressed with their low sexual desire. Moreover, psychometric analyses revealed that kisspeptin improved ‘happiness about sex’ reported by the boys.

Dr Comninos and Professor Dhillo now plan to take this forward with larger scale studies, studies in numerous populations and collaborations to develop kisspeptin as a sensible treatment for each men and women with distressing psychosexual disorders.