Kisspeptin

What it is

Kisspeptin is not one molecule but a small family of related signaling peptides, all cut from the same parent protein made from the KISS1 gene. Its main job in the body is to switch on nerve cells that release a hormone called GnRH, which in turn tells the pituitary gland to release two further hormones, LH and FSH, that drive the reproductive system.

Researchers use two main forms in studies, a shorter ten amino acid fragment called kisspeptin ten and a longer fifty four amino acid form called kisspeptin fifty four, which tends to stay active longer. Beyond the reproductive hormone system, separate research has looked at kisspeptin's effect on brain activity tied to sexual desire and attraction, since the same signaling pathway appears to reach brain regions involved in those processes.

How it is studied

Human studies of kisspeptin have used a nasal spray form of the longer fragment in healthy men and women and in patients with a reproductive disorder called hypothalamic amenorrhea, where periods stop because the brain signal to the ovaries is disrupted, plus slow intravenous infusions of the compound in adults diagnosed with hypoactive sexual desire disorder, a persistent, distressing lack of interest in sex. Researchers measured blood hormone levels, brain activity on functional MRI scans while participants viewed sexual or facial images, and self-reported measures of desire and arousal. All of the trials found for this entry were single-session, crossover designs comparing kisspeptin against a placebo infusion or spray in the same participants; none gave kisspeptin repeatedly over weeks or months.

What studies report

• A randomized, placebo-controlled trial of a nasal spray form of kisspeptin fifty four reported that it raised luteinizing hormone, a signal that drives the reproductive system, above placebo levels in healthy men, healthy women, and women with hypothalamic amenorrhea, with no side effects reported in any group. [1]
• A randomized, placebo-controlled trial in men diagnosed with hypoactive sexual desire disorder reported that a kisspeptin infusion changed brain activity in regions tied to sexual processing while participants viewed sexual images, compared with a placebo infusion. [2]
• That same trial in men reported a secondary finding of increased penile firmness in response to sexual images, described as up to 56 percent greater than during the placebo infusion, along with higher self-reported happiness about sex. [2]
• A companion randomized, placebo-controlled trial in women diagnosed with hypoactive sexual desire disorder reported that a kisspeptin infusion changed brain activity in regions tied to processing erotic images and attractive faces, compared with placebo. [3]

What is not known

All of the human trials located for this entry tested a single spray or a single 75 minute infusion, so it is not known whether these hormone and brain activity changes would hold up with repeated use over weeks or months. The sexual desire trials enrolled adults already diagnosed with hypoactive sexual desire disorder, so it is not known whether kisspeptin has a similar effect in people without that diagnosis. Most of the sexual desire findings involve brain imaging and secondary behavioral measures rather than a single, clear-cut symptom score, and no trial has yet tested kisspeptin as an approved treatment for either fertility or sexual desire.

Reported adverse findings

• The nasal spray trial reported no side effects or adverse events in any of the three groups tested. [1]
• The infusion trial in women reported that kisspeptin was well tolerated with no reported adverse effects. [3]

Regulatory status

Kisspeptin has not been approved as a drug by the United States Food and Drug Administration or Health Canada. It remains a research compound studied mainly in specialized fertility and endocrinology research settings.