Kisspeptin-10

Kisspeptins are made by neurons in the hypothalamus and are the main switch for the reproductive axis: they stimulate the neurons that release GnRH, which in turn drives the pituitary to release LH and FSH. People born with loss-of-function variants in the kisspeptin receptor do not go through puberty [5][6]. The kisspeptin gene produces peptides of 54, 14, 13 and 10 amino acids that share the same C-terminal ten; kisspeptin-10 is that shared end (sequence YNWNSFGLRF-amide) [2][7].

Men. The first dose-finding study in healthy men found that intravenous boluses raised LH within 30 minutes, most strongly at 1 µg/kg (4.1 to 12.4 IU/L); 3 µg/kg gave a smaller rise. A 22.5-hour infusion raised testosterone from 16.6 to 24.0 nmol/L, and a lower-dose infusion increased the number and size of LH pulses [1]. In five obese men with type 2 diabetes and low testosterone, the LH response to a bolus was similar to that of healthy men, and an 11-hour infusion raised testosterone from 8.5 to 11.4 nmol/L [3]. The authors proposed kisspeptin agonists as a way to raise the body's own testosterone in such men [3].

Longer use. A 2026 randomised, single-blind study tested ways of giving it under the skin by pump. Continuous infusion for 5 days kept testosterone up, but LH and FSH fell back to placebo levels. Eight hours a day for 12 days, however, kept LH raised throughout, and a bolus on day 12 still worked, showing that the receptor had not shut down [8]. A 24-hour intravenous infusion in three men raised LH five- to eightfold, peaking at 12–20 hours and then drifting down 13–47% while the infusion continued [9].

Women. Responses depend on the menstrual cycle. Early in the follicular phase, even large intravenous or subcutaneous doses of kisspeptin-10 did not change LH or FSH, while the same dose worked in the preovulatory phase [4]. Another study found LH pulses after a bolus in every woman in the luteal and preovulatory phases but in only half of those in the early follicular phase [10].

Upstream defects. In four patients whose puberty failed because of mutations in neurokinin B or its receptor, a continuous kisspeptin-10 infusion restored LH pulses and raised sex steroids, showing that kisspeptin acts downstream of neurokinin B [11].

What kisspeptin-10 has not been tested for. The trials of kisspeptin for sexual desire and arousal, IVF egg maturation and hypothalamic amenorrhoea all used the longer kisspeptin-54, which lasts longer in the blood [12][13][14]. In 32 men with low sexual desire, a 75-minute kisspeptin-54 infusion increased penile rigidity in response to erotic video by up to 56% over placebo and changed activity in sexual-processing brain regions [12]; a matching trial in 32 women changed brain responses to erotic and attraction cues [15]. Earlier imaging work in healthy men found kisspeptin-54 enhanced limbic responses to sexual and couple-bonding images [16][17][18]. As an IVF trigger, kisspeptin-54 matured eggs in 95% of 60 women at high risk of hyperstimulation, none of whom developed moderate or severe OHSS [13]. Reviews see a therapeutic future for kisspeptins in these areas [5][6][19], but whether kisspeptin-10 shares these effects is untested.

Kisspeptin-10 binds the kisspeptin receptor (KISS1R, also called GPR54) on GnRH neurons, which release GnRH into the pituitary portal blood; LH follows within minutes [1][5]. Continuous infusion increased LH pulse frequency in healthy men, so kisspeptin speeds up the GnRH pulse generator rather than only triggering single releases [1], and it restored pulsatility in patients who lack neurokinin B signalling [11]. Testosterone follows the rise in LH over hours [1].

Why kisspeptin-10 is weaker than kisspeptin-54 in the body is partly explained by pharmacokinetics: in mice, kisspeptin-10 had a half-life of about 4 minutes against 32 minutes for kisspeptin-54, and only kisspeptin-54 activated GnRH neurons behind the blood-brain barrier after injection. Repeated injections of kisspeptin-10 every 10 minutes still did not reproduce the long LH release, suggesting that clearance is not the whole story [2].

With continuous exposure the receptor response fades: LH returned to baseline after 5 days of continuous subcutaneous infusion, and declined within the first day of intravenous infusion, while intermittent 8-hour exposure preserved it [8][9].

No adverse events were reported in the first dose-finding study in men [1]. The published human studies are small and short, so there is no evidence either way on long-term use. The kisspeptin-54 trials in men and women with low sexual desire reported no side effects or adverse events [12][15].

The expected effects come from the hormones it raises: LH, FSH and testosterone. Continuous exposure desensitises the LH response within days [8]. In women, the effect varies with the menstrual cycle [4]. Kisspeptin-10 is not approved for any medical use.