The hormone kisspeptin could be used to treat women and men distressed by their low sexual desire, according to two new studies.

The studies, both published in JAMA Network Open, found that giving kisspeptin can boost sexual responses in women and men who have hypoactive sexual desire disorder (HSDD) – a condition characterised by low sexual desire that is distressing to the individual. HSDD affects up 10 percent of women and 8 percent of men worldwide and can 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, part of UK Research and Innovation.

We provide the first evidence that kisspeptin is a potentially safe and effective therapy for both women and men with distressing low sexual desire. 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 author of the study

Kisspeptin is a naturally-occurring hormone that stimulates the release of other reproductive hormones inside 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 effects in women and men with low sexual desire for the first time.

These two clinical trials involved 32 pre-menopausal women and 32 men with HSDD. In both studies, patients underwent scanning of the brain using MRI, as well as blood and behavioural tests. Kisspeptin administration improved sexual brain processing in both women and men, resulting in positive effects on sexual behaviour compared to placebo. These are the first clinical studies to explore the ability of kisspeptin to boost sexual pathways in women and men distressed by their low sexual desire.

Kisspeptin-based treatments

The researchers believe that the results lay the foundations for kisspeptin-based treatments for women and men 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 author of the study, said:

“Low sexual desire can be distressing and so result in HSDD. This can have a major detrimental impact on relationships, mental health, and fertility. Even though it is relatively common, treatment options in women are limited, carry significant side-effects and in some cases can 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. Therefore, there is a real unmet need to find new, safer and more effective therapies for this distressing condition for both women and men seeking treatment.

“Our two studies provide proof-of-concept for the development of kisspeptin treatments, as we provide the first evidence that kisspeptin is a potentially safe and effective therapy for both women and men with distressing low sexual desire. Additionally in men, we demonstrate that kisspeptin can have positive effects not only in the brain but also in the penis by increasing rigidity. Furthermore, kisspeptin was well-tolerated by both women and men with no side-effects reported, which is crucial from a drug development point of view. We now plan to take things forward to hopefully realise the potential of kisspeptin therapeutics in psychosexual disorders - sexual problems which are psychological in origin, such as 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 author of the study, added:

“Our studies build on our previous work to assess the effectiveness of kisspeptin and its boosting effects in terms of arousal and attraction. It is highly encouraging to see the same boosting effect in both women and men, although the precise brain pathways were slightly different as might be expected.

“Collectively, the results suggest that kisspeptin may offer a safe and much-needed treatment for HSDD that affects millions of people around the world and we look forward to taking this forward in future larger studies and in other patient groups.”

Boosting effect

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

32 pre-menopausal heterosexual women with HSDD (aged 19-48 years) completed two study visits, one for administration of kisspeptin and another visit for placebo. Participants completed psychometric questionnaires before and towards the end of kisspeptin or placebo administration to assess their mood and behaviour. 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. They also found that women who were more distressed by their sexual function showed greater kisspeptin-enhanced brain activity in the hippocampus (a key structure implicated in female sexual desire). Furthermore, the more kisspeptin activated the posterior cingulate cortex - a key behavioural brain area - in response to attractive male faces, the less sexual aversion was reported by participants. Crucially, the psychometric analyses revealed that the women reported feeling ‘more sexy’ during kisspeptin, compared to placebo.

Improved sexual desire

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

Collectively, the results suggest that kisspeptin may offer a safe and much-needed treatment for HSDD that affects millions of people around the world. Professor Waljit Dhillo NIHR Senior Investigator, from the Department of Metabolism, Digestion and Reproduction at Imperial College London, Consultant Endocrinologist at Imperial College Healthcare NHS Trust and co-senior author of the study

The study demonstrated that kisspeptin significantly boosted brain activity in key structures of the sexual brain network while also increasing penile rigidity by up to 56 per cent compared to 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. Furthermore, psychometric analyses revealed that kisspeptin improved ‘happiness about sex’ reported by the men.

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

ENDS  

*Peter's* story

*Peter* (age 44)

*Name changed*

“I got involved in the trial because I had previous problems with my sexual appetite and performance.

“The issue had always been detrimental to sustaining relationships. I would often make excuses as to why my sexual appetite was low. For example, I would blame stress at work or tiredness as a reason instead of being honest. I had tried other performance supporting medication like Viagra. However, this proved ineffective as the issue was simply one of low desire. It was highly embarrassing and not something I felt able to talk to my previous partners about. I feared they would confuse it with lack of attraction to them.

“I was keen to learn whether there was a solution to my problem and learn more about my condition.

“I received the kisspeptin infusion in June 2021 and I noticed a difference in terms of my sexual desire. The week I had the kisspeptin infusion we conceived our son, who was born in March 2022. I had the best possible outcome as a result of the trial. 

“I also learnt a lot more about myself and my condition. I am really pleased to have contributed to this trial, which has been life-changing for me. I’m glad that others in a similar position could benefit from the treatment. 

*Eve's* story

*Eve* (43)

*Name changed*

“I took part in the trial as I was experiencing low sexual libido. Initially, I put it down to having small children and being exhausted as a result. However, this continued and started to impact my wellbeing. I wanted to see whether there was another reason for why I was feeling this way. 

“I had two study visits in 2020 where I received the placebo and the kisspeptin infusions without knowing which one I was getting at the time. I did notice a bit of a difference once I received the kisspeptin infusion and it was fascinating to be part of the process.

“I am glad that I took part in the study as many women wouldn’t like to admit they are experiencing this and may not seek help. I’m glad to know that kisspeptin could be a treatment option for other women.”