Kisspeptin and Hypoactive Sexual Desire Disorder

Take-home points

• 37 participants with hypoactive sexual desire disorder received a 75–minute infusion of kisspeptin or placebo.
• Those who received kisspeptin observed increased activity in key sexual-processing regions in the brain.
• Kisspeptin was also increased penile tumescence by 56% compared to placebo.
• Although promising findings, longer term studies are needed to confirm its efficacy as a treatment option for hypactive sexual desire disorder.

New advances in hypoactive sexual desire disorder treatment

A new study conducted at Imperial College London was recently published in JAMA, exploring the effect of kisspeptin infusion on sexual brain processing in men with low sexual desire due to hypoactive sexual desire disorder (HSDD).¹  

Kisspeptin is a neuropeptide, a hormone that acts within the brain in the hypothalamus to regulate reproductive hormones in men and women. These hormones include gonadotrophin- hormones (GnRH) which are responsible for releasing luteinizing and follicle-stimulating hormones from the pituitary gland.  

What is luteinizing hormone?

• A hormone that stimulates the testes to make testosterone  

What is follicle-stimulating hormone?

• A hormone that binds and transports testosterone around the body – and works to control the amount of sex hormones actively working in the body

Earlier studies conducted on animals showed that infusing kisspeptin heightened sexual motivation and response to sexual stimuli, lowered sexual aversion, and increased erections. This led researchers to explore whether these effects could be reproduced in men who experience a lack of sexual desire, a condition also known as hypoactive sexual desire disorder (HSDD).

Study title:

• Kisspeptin regulates Sexual Brain Processing and Penile Tumescence in Men with Hypoactive Sexual Desire Disorder  

What did they do?

Researchers took 37 men and randomly allocated them to receive a 75-minute infusion of kisspeptin or placebo. During the infusion, participants watched a short and long video task containing sexually explicit content to measure sexual response. Blood samples were obtained to measure hormonal changes before and during the infusion of kisspeptin. Arousal, sexual desire, and penile tumescence were also recorded. The primary outcome was the change in brain response to sexual stimuli. The main secondary outcomes included changes in behavioural measures of sexual desire and arousal, mood, anxiety, nonsexual attention, and penile tumescence.  

What did they find?

During the sexual videos, kisspeptin significantly increased activity in key sexual-processing brain structures compared to the placebo. These included regions such as the globus pallidus and the posterior cingulate cortex, both involved in regulating arousal. Additionally, kisspeptin increased the tumescence of the penis by 56% more than placebo throughout the long sexual video.  

What is penile tumescence?

• An erection of the penis

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What are the study conclusions?

This trial provides clinical evidence showing kisspeptin administration in men with HSDD increases activity in key regions within the brain responsible for eliciting feelings of sexual arousal. The added benefit of increasing penile tumescence suggests kisspeptin could help with men suffering from erectile dysfunction.  

How should we interpret this data?

This study provides promising data to support the potential utility of kisspeptin in treating men with HSDD. However, several important issues need to be considered. Firstly, longer-term data is needed to determine whether or not kisspeptin can hold meaningful and long-term benefits in men with HSDD.  

Secondly, one of the main challenges of administering kisspeptin is that it rapidly degrades in the body and is, therefore, ineffective when taken orally. Researchers will need to explore how to improve the pharmacokinetics to allow for a practical and effective route of administration. Despite these limitations, kisspeptin appears to be an exciting molecule that may in future, prove to be a useful treatment for men with a variety of sexual issues.  

References

1. Mills EG, et al. JAMA 2023;6(2):e2254313. doi:10.1001/jamanetworkopen.2022.54313.