Kisspeptin-10

Kisspeptin-10 is a truncated form of the endogenous neuropeptide kisspeptin, a master upstream regulator of the hypothalamic-pituitary-gonadal (HPG) axis. It plays a critical role in puberty onset, reproductive function, and hormone regulation. It is actively investigated as a diagnostic tool for reproductive disorders and a potential fertility treatment.

Kisspeptin-10 binds the KISS1R (GPR54) receptor on GnRH neurons in the hypothalamus, stimulating pulsatile GnRH release. This triggers LH and FSH secretion from the pituitary, subsequently driving testosterone or estrogen production. Unlike GnRH agonists, kisspeptin stimulates GnRH release physiologically, preserving pulsatility. Also has metastasis-suppressor activity via KISS1R in certain cancers.

No approved indications. Research: hypothalamic amenorrhea, IVF protocols, hypogonadism diagnosis, low libido, GnRH neuron function assessment.

Human studies at Imperial College London demonstrated that kisspeptin infusion restores LH pulsatility in women with hypothalamic amenorrhea. Shown to stimulate LH/FSH release in both men and women. Phase II trials for IVF oocyte maturation showed promising results with lower OHSS risk than hCG trigger. Active research programs ongoing.

Generally well-tolerated in clinical trials. Very short half-life limits systemic exposure. Possible flushing, headache. Theoretical concern about tachyphylaxis with continuous administration (may suppress HPG axis paradoxically). No serious adverse events reported in published trials.

Investigational. Active clinical research programs. Potential for FDA approval as a diagnostic agent or IVF adjunct. No approved formulations.

Drug Interactions: May interact with GnRH agonists/antagonists, hormonal contraceptives. Monitoring: LH, FSH, testosterone/estradiol, GnRH response. Research Gaps: Optimal dosing for therapeutic (vs. diagnostic) use. Long-acting analogs needed for practical therapy. Cancer metastasis suppression potential unexplored clinically.