Kisspeptin-10

Overview

Kisspeptin-10 (KP-10) is the 10-amino-acid C-terminal fragment of kisspeptin (the KISS1 gene product, also called metastin) that retains full biological activity. It is an investigational signaling peptide that sits at the top of the reproductive axis and is studied for fertility, hypogonadism, and as a diagnostic challenge. It is not FDA-approved.

Mechanism of Action

Kisspeptin-10 binds KISS1R (GPR54) on GnRH neurons in the hypothalamus, triggering pulsatile GnRH release. GnRH then drives LH and FSH secretion from the anterior pituitary, which stimulates downstream gonadal sex hormone production. Kisspeptin signaling is recognized as the upstream regulator of HPG-axis onset at puberty.

Research Summary

Clinical research (largely from the Dhillo group at Imperial College London) shows IV kisspeptin-10 boluses or infusions stimulate LH pulses in healthy men and in men with hypogonadotropic hypogonadism, and kisspeptin-54 has been studied as an IVF oocyte-maturation trigger with lower OHSS risk than hCG. Ongoing trials explore hypoactive sexual desire disorder (HSDD), unexplained infertility, and delayed puberty. Widely sold grey-market SubQ use (~200 mcg 2x/week for libido or as an HRT-style boost) is not clinically validated.

Dosing Information

Reported Side Effects

• Transient flushing
• Mild headache
• Injection site discomfort
• Generally well tolerated at research doses

Research References

• Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men (George et al., JCEM) (2011)
• Kisspeptin restores pulsatile LH secretion in patients with neurokinin B signaling deficiencies (Young et al., Neuroendocrinology) (2012)
• The GPR54 gene as a regulator of puberty (Seminara et al., NEJM) (2003)