An infusion of the hormone kisspeptin helped improve low sexual desire in both men and women, two small trials found.

In the 37-participant study of heterosexual men with hypoactive sexual desire disorder (HSDD), IV kisspeptin-54 significantly increased activity in key sexual-processing structures of the brain in response to viewing sexual videos compared with placebo (mean absolute change Cohen d 0.81, 95% CI 0.41-1.21, P=0.003), reported Alexander Comninos, MD, PhD, of Imperial College London, and colleagues.

This was mainly driven by significantly enhanced activation in the left middle frontal gyrus, left anterior cingulate cortex, and deactivation in the bilateral parahippocampus measured by functional MRI (fMRI), the researchers wrote in JAMA Network Open.

“We demonstrate that kisspeptin can have positive effects not only in the brain but also in the penis by increasing rigidity,” Comninos said in a statement. The treatment increased penile tumescence up to 56% more than placebo in response to sexual stimuli (mean difference 0.28 units, 95% CI 0.04-0.52, P=0.02).

Meeting another secondary outcome, kisspeptin significantly increased behavioral measures of sexual desire, particularly happiness about sex (mean difference 0.63 points, 95% CI 0.10-1.15, P=0.02).

Men more distressed by low sexual desire at baseline tended to see greater kisspeptin-enhanced brain activity in the posterior cingulate cortex at the start of the trial.

“The neuropeptide kisspeptin is a crucial endogenous activator of the reproductive system, with extensive distribution throughout the rodent and human brain,” the researchers explained in their study, adding that animal studies have suggested the hormone can play a role in modulating reproductive behavior.

“Low sexual desire can be distressing and so result in HSDD,” Comninos said. “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,” he said. And for men, “there are currently no licensed treatments and none on the horizon.”

Kisspeptin in Women

Back in October 2022, Comninos’ group published the results of a 40-participant trial of the same IV kisspeptin therapy in premenopausal women with HSDD.

In findings that also appeared in JAMA Network Open, kisspeptin therapy similarly affected certain regions of the brain related to sexual and facial attraction brain processing. This included deactivation of the left inferior frontal gyrus (Z max 3.76, P=0.01), activation of the right postcentral and supramarginal gyrus (Z max 3.73, P<0.001), and deactivation of the right temporoparietal junction (Z max 4.08, P=0.02).

There was also a positive correlation between kisspeptin-enhanced hippocampal activity in response to erotic videos and baseline distress relating to sexual function (r 0.469, P=0.007). There was also a correlation seen between reduced sexual aversion and enhancement of posterior cingulate cortex activity in response to attractive male faces (r 0.476, P=0.005).

Trial Details

In both double-blind crossover trials, men and women received IV infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or matching placebo.

Starting 30 minutes into the infusion, kisspeptin bioactivity was confirmed, with circulating levels rising to a steady state for the rest of the infusion at minutes 30 to 75 (increasing an average of 2,705 pmol/L for men and 1,305 pmol/L for women).

This was also paired with a significant increase in luteinizing hormone and follicle-stimulating hormone levels in both sexes. There were no changes in testosterone, cortisol, estradiol, or progesterone.

At the 30-minute mark, fMRI brain scans measured blood oxygen level-dependent activity in response to visual sexual stimuli (short videos of sexual activities alternating with control videos of people exercising).

Female participants were given a facial attraction task, involving male and female faces of medium and high attractiveness. Men watched 12 minutes of the alternating short videos, followed by a continuous 8-minute video of a heterosexual couple engaging in sexual activities where objective arousal (measured using penile tumescence) and subjective arousal (using a magnetic resonance-compatible scroll wheel) were recorded. The biggest proerectile effects were seen at the end of the 8-minute video task.

A week later, participants crossed over interventions, receiving treatment if they previously received placebo. The average age of females was 29.2 and of males was 37.9.

Kisspeptin treatment was safe and well-tolerated without any significant adverse events reported for either sex, “which is crucial from a drug development point of view,” said Comninos. There also wasn’t any impact seen on blood pressure or heart rate.

“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,” he said, emphasizing the large unmet need for new and effective therapies for both men and women experiencing HSDD.

“We now plan to take things forward to hopefully realize the potential of kisspeptin therapeutics in psychosexual disorders — sexual problems which are psychological in origin, such as unexplained low libido,” he concluded, stating plans for larger scale studies of kisspeptin.

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