Kisspeptin-54
The full-length kisspeptin, trialled as a trigger for egg maturation in IVF because it does not appear to cause ovarian hyperstimulation
Kisspeptin-54 is the long form of kisspeptin, the hypothalamic peptide that drives GnRH release. Its furthest-developed use is a single injection to trigger egg maturation in IVF: in 60 women at high risk of ovarian hyperstimulation syndrome, eggs matured in 95% and nobody developed a moderate or worse case. It is investigational.
What is it?
Kisspeptin acts on the hypothalamus to release GnRH, which in turn releases luteinising hormone (LH) and follicle-stimulating hormone. Kisspeptin-54 is its full-length circulating form, and because it works upstream of GnRH it produces a hormone surge closer to a natural cycle than the hCG injection ordinarily used to trigger egg maturation in IVF.
The response depends on context. In healthy women it was small early in the cycle and large just before ovulation, and in healthy men GnRH itself released about twice as much LH as kisspeptin-54. That gentler, cycle-dependent push is the rationale for IVF: enough to trigger eggs, less likely to overstimulate.
In 53 women having IVF, a single injection at 1.6 to 12.8 nmol/kg matured eggs at every dose and 23% had a clinical pregnancy. A phase 2 trial then gave it to 60 women at high risk of ovarian hyperstimulation syndrome: eggs matured in 95%, live birth followed 45% of transfers, and nobody developed moderate or worse hyperstimulation. A second dose 10 hours later helped women whose first response was weak.
Hypothalamic amenorrhoea, where periods stop because the brain's signal fails, was another target. A single injection raised LH strongly, but twice-daily injections lost their effect within two weeks; twice-weekly dosing desensitised only partly and kept hormones up for eight weeks, and infusion restored LH pulses. None of this has become a treatment.
Outside fertility it has been used as a test of the hypothalamus: given to 21 men with congenital hypogonadotropic hypogonadism and 21 healthy men, a 6.4 nmol/kg bolus separated the groups completely. Older men responded as well as younger ones. It did not change blood pressure. It is approved nowhere, its trials are small and mostly from one London group, and WADA names it.
Mechanism of Action
Kisspeptin-54 activates the kisspeptin receptor (KISS1R, also called GPR54) on GnRH neurons, which release GnRH and so drive LH and FSH from the pituitary.
Upstream of GnRH
Acts on the hypothalamus rather than the pituitary; men with congenital GnRH deficiency barely respond, which is why it works as a diagnostic test.
Cycle-dependent LH release
In women the LH response is far larger just before ovulation than early in the cycle.
Tachyphylaxis
Twice-daily injections lose effect within about two weeks; twice-weekly dosing desensitises only partly.
Published Research
The studies behind kisspeptin-54, read from their PubMed abstracts.
Phase 2: 60 women at high risk of hyperstimulation
A single injection of 3.2 to 12.8 nmol/kg triggered egg maturation in 95% of women. Across doses, 53% had a clinical pregnancy and 45% a live birth per transfer. No woman developed moderate, severe or critical ovarian hyperstimulation syndrome.
First IVF trigger trial: 53 women
A single injection of 1.6 to 12.8 nmol/kg after superovulation matured eggs at every dose, with more mature eggs at higher doses. Embryos were transferred in 92% of patients; 23% had a clinical pregnancy.
Telling the hypothalamus apart from the pituitary: 42 men
21 men with congenital hypogonadotropic hypogonadism and 21 healthy men received 6.4 nmol/kg. Peak LH was 12.5 IU/L in healthy men and 0.4 in affected men, separating the groups better than GnRH did.
A week of twice-daily injections: 10 healthy women
6.4 nmol/kg twice daily on days 7 to 14 of the cycle, against saline. Menstrual cycles continued in everyone and the response to a later injection was not blunted; cycles were about two days shorter and the LH peak came earlier.
Ovarian cells after a kisspeptin trigger: 48 women
Granulosa lutein cells from women triggered with kisspeptin-54 expressed more of the genes behind ovarian steroid production, including the FSH and LH receptors and aromatase, than cells from women triggered with hCG or a GnRH agonist.
A second dose rescues weak responders
In 62 women at high risk of hyperstimulation, a second kisspeptin-54 injection 10 hours after the first raised the share with at least 60% of follicles yielding eggs from 45% to 71%, without more over-response.
Daily injections wear off
In women with hypothalamic amenorrhoea, a first injection raised LH by 24.0 IU/L, but after two weeks of twice-daily injections the rise was only 2.5 IU/L; the pituitary still responded to GnRH.
Twice weekly works better
In women with hypothalamic amenorrhoea, twice-daily injections produced near-complete tolerance while twice-weekly injections desensitised only partly, and eight weeks of twice-weekly treatment raised reproductive hormones against saline without adverse effects.
Restoring LH pulses by infusion
In women with hypothalamic amenorrhoea, intravenous infusion tripled LH pulses (5.0 against 1.6 per 8 hours) and raised pulse size about sixfold, with the best dose differing between women.
Strongest just before ovulation
In healthy women, doses of 0.2 to 6.4 nmol/kg raised LH in a dose-dependent way, with a far bigger response in the preovulatory phase (20.6 IU/L) than the follicular phase (0.1).
Against kisspeptin-10 and GnRH
In healthy men given equal infusions, GnRH raised LH about twice as much as kisspeptin-54 and three times as much as kisspeptin-10.
Older men still respond
Healthy older men had at least as large an LH response to kisspeptin-54 as young men, but a smaller testosterone rise, pointing to an ageing testis rather than hypothalamus.
No effect on blood pressure
Kisspeptin-54 injection did not change heart rate or blood pressure in healthy men or women, and plasma kisspeptin did not differ in hypertensive disorders of pregnancy.
Dosing Data
There is no approved dose. Trials used single subcutaneous injections of 1.6 to 12.8 nmol/kg to trigger egg maturation in IVF, and 6.4 nmol/kg as a diagnostic bolus.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the human trials above.
Contraindications & Cautions
Kisspeptin-54 has no label. These cautions follow from what the trials did and did not test.
Legal Status
Kisspeptin-54 is investigational, and prohibited in sport.
Frequently Asked Questions
?What is kisspeptin-54?
The full-length form of kisspeptin, the hypothalamic peptide that triggers GnRH release and, through it, LH and FSH.
?Why is it studied in IVF?
As a trigger for egg maturation it acts upstream of GnRH, and in 60 women at high risk of ovarian hyperstimulation syndrome nobody developed a moderate or worse case.
?What dose did the trials use?
A single subcutaneous injection of 1.6 to 12.8 nmol/kg as an IVF trigger, and a 6.4 nmol/kg bolus as a hypothalamic test.
?Is it approved?
No. Drugs@FDA holds no application for it, as of September 30, 2026, and WADA prohibits kisspeptin in sport.
?Why can it not simply be injected daily?
Because the body stops responding. In women with hypothalamic amenorrhoea, twice-daily injections lost almost all their effect on LH within two weeks, while twice-weekly injections kept working partially for eight weeks.
References
- [fda] FDA. Drugs@FDA (openFDA): no application for kisspeptin. Read September 30, 2026.
- [pubmed] Abbara A, et al. "Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy." J Clin Endocrinol Metab, 2015;100(9):3322-31. PMID: 26192876.
- [pubmed] Jayasena CN, et al. "Kisspeptin-54 triggers egg maturation in women undergoing in vitro fertilization." J Clin Invest, 2014;124(8):3667-77. PMID: 25036713.
- [pubmed] Abbara A, et al. "Kisspeptin-54 Accurately Identifies Hypothalamic Gonadotropin-Releasing Hormone Neuronal Dysfunction in Men with Congenital Hypogonadotropic Hypogonadism." Neuroendocrinology, 2021;111(12):1176-1186. PMID: 33227799.
- [pubmed] Jayasena CN, et al. "Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual cyclicity in healthy female volunteers." J Clin Endocrinol Metab, 2013;98(11):4464-74. PMID: 24030945.
- [pubmed] Owens LA, et al. "The direct and indirect effects of kisspeptin-54 on granulosa lutein cell function." Hum Reprod, 2018;33(2):292-302. PMID: 29206944.
- [pubmed] Dhillo WS, et al. "Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males." J Clin Endocrinol Metab, 2005;90(12):6609-15. PMID: 16174713.
- [pubmed] Abbara A, et al. "A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial." Hum Reprod, 2017;32(9):1915-1924. PMID: 28854728.
- [pubmed] Jayasena CN, et al. "Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis." J Clin Endocrinol Metab, 2009;94(11):4315-23. PMID: 19820030.
- [pubmed] Jayasena CN, et al. "Twice-weekly administration of kisspeptin-54 for 8 weeks stimulates release of reproductive hormones in women with hypothalamic amenorrhea." Clin Pharmacol Ther, 2010;88(6):840-7. PMID: 20980998.
- [pubmed] Jayasena CN, et al. "Increasing LH pulsatility in women with hypothalamic amenorrhoea using intravenous infusion of Kisspeptin-54." J Clin Endocrinol Metab, 2014;99(6):E953-61. PMID: 24517142.
- [pubmed] Dhillo WS, et al. "Kisspeptin-54 stimulates gonadotropin release most potently during the preovulatory phase of the menstrual cycle in women." J Clin Endocrinol Metab, 2007;92(10):3958-66. PMID: 17635940.
- [pubmed] Jayasena CN, et al. "Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men." Hum Reprod, 2015;30(8):1934-41. PMID: 26089302.
- [pubmed] Abbara A, et al. "Hypothalamic Response to Kisspeptin-54 and Pituitary Response to Gonadotropin-Releasing Hormone Are Preserved in Healthy Older Men." Neuroendocrinology, 2018;106(4):401-410. PMID: 29544222.
- [pubmed] Nijher GM, et al. "The effects of kisspeptin-54 on blood pressure in humans and plasma kisspeptin concentrations in hypertensive diseases of pregnancy." Br J Clin Pharmacol, 2010;70(5):674-81. PMID: 21039761.
Sources & Citations
Studies were read from their PubMed abstracts; there is no approved label. Read October 6, 2026.
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