Kisspeptin-10

What the published research shows

The cited literature examined kisspeptin-10 as the C-terminal kisspeptin decapeptide^2,8. Human studies investigated circulating luteinising hormone (LH), follicle-stimulating hormone (FSH), gonadal steroids and LH pulse patterns in healthy volunteers and in patients with TAC3 or TACR3 mutations. In these studies, gonadotropin-releasing hormone (GnRH) activity was inferred from circulating LH; endogenous GnRH secretion was not measured directly^{1,2,3,4,5,6,7}.

Evidence base: Seven human studies: five physiological investigations in healthy volunteers, including one single-blind, placebo-controlled comparison^1,2,3,4,5; one open study in four patients with TAC3 or TACR3 mutations⁶; and one randomised, single-blind, placebo-controlled study in healthy men, with 15 men recruited and 12 men reported as controls⁷. An additional study examined three juvenile agonadal male rhesus monkeys⁸. The human evidence was limited to small physiological studies with hormone end points. The literature search identified no randomised placebo-controlled trial with clinical end points and no dedicated safety or toxicology study.

Key studies at a glance

Changes in LH and FSH AUC in women (George 2012)

Effects reported in the studies

• LH concentrations and pulse amplitude. In the group of six healthy men with the largest observed LH response in George 2011, serum LH rose from 4.1 ± 0.4 to 12.4 ± 1.7 IU/l (p < 0.001)¹. In Chan 2011, involving 13 healthy men, an immediate LH pulse was observed regardless of the timing of the previous endogenous pulse. Its mean amplitude was 5.0 ± 1.0 vs 2.1 ± 0.3 mIU/ml for endogenous pulses (p = 0.02)².
• LH pulse frequency and timing. In four healthy men in George 2011, LH pulse frequency rose from 0.7 ± 0.1 to 1.0 ± 0.2 pulses/h (p < 0.05), alongside a rise in mean LH from 5.2 ± 0.8 to 14.1 ± 1.7 IU/l (p < 0.01)¹. In the 13 healthy men studied by Chan 2011, the next endogenous LH pulse was delayed by an interval approximating the normal interval between pulses. The authors inferred changes in GnRH activity from the LH pulse pattern².
• Testosterone and LH concentrations. In another protocol involving four healthy men in George 2011, serum testosterone rose from 16.6 ± 2.4 to 24.0 ± 2.5 nmol/l (p < 0.001), while LH rose from 5.4 ± 0.7 to 20.8 ± 4.9 IU/l (p < 0.05). These were hormone measurements within a physiological experiment¹.
• Differences by sex, cycle phase and sex-steroid status. In healthy men and women studied by Jayasena 2011 (n = 4–5 per group), LH and FSH rose in men and preovulatory women, while no gonadotropin change was observed in follicular-phase women³. In the separate George 2012 study, women in the early follicular phase did show an LH AUC increase. Post-menopausal women had the largest LH and FSH responses, while women using the combined pill had no statistically significant LH change. A significant FSH rise was reported only in post-menopausal women⁴.
• Comparison with kisspeptin-54 and GnRH. In healthy men in Jayasena 2015 (n = 5 per group), mean LH AUC, as stated in the abstract, was 10.81 ± 1.73 h·IU/l with kisspeptin-10, 14.43 ± 1.27 h·IU/l with kisspeptin-54 and 34.06 ± 5.18 h·IU/l with GnRH. The GnRH comparison gave p < 0.001 vs kisspeptin-10 and p < 0.01 vs kisspeptin-54. The abstract also reported different plasma kisspeptin immunoreactivity AUC values: 179 ± 24 h·pmol/l for kisspeptin-10 and 6650 ± 397 h·pmol/l for kisspeptin-54⁵.
• LH pulses in patients with TAC3 or TACR3 mutations. In four patients with congenital hypogonadotropic hypogonadism, LH pulses appeared in the three patients who previously had no detectable pulses, while the fourth patient had more pulses. Mean pulse frequency was 0.5 pulses/h, compared with 0.7 pulses/h described for healthy men in the authors’ studies; pulse amplitude and LH AUC remained below those reference values. Gonadal steroids and inhibin B also rose, and FSH increased approximately 1.7-fold on average⁶.
• Differences between experimental protocols. In healthy men in Yeung 2026, LH, FSH and testosterone rose compared with vehicle (p < 0.0001). In one protocol, gonadotropin concentrations later resembled vehicle values while testosterone remained elevated; another protocol retained a gonadotropin rise. The abstract did not provide a unit for its numerical LH-change values⁷.

Adverse effects and tolerability reported

• Reported absence of related adverse events in four patients. In the open study of four patients with TAC3 or TACR3 mutations, no adverse events related to kisspeptin-10 or vehicle were reported. This observation came from the small patient study described above⁶.
• Missing adverse-event and tolerability results. In studies of healthy men and women, the available abstracts of George 2011, Chan 2011, Jayasena 2011, George 2012 and Yeung 2026 did not provide adverse-event or tolerability data^1,2,3,4,7. For the healthy men studied in Jayasena 2015, neither the abstract nor the available full text reported study-specific adverse-event results; no adverse-event section was identified⁵. Missing reporting did not establish an absence of adverse effects.
• Attenuation of the hormonal response in healthy men. In one protocol in Yeung 2026, gonadotropin concentrations later resembled vehicle values despite testosterone remaining elevated. This was a pharmacological observation; the abstract did not report adverse-event data⁷.
• Receptor desensitisation in rhesus monkeys. In three GnRH-primed juvenile agonadal male rhesus monkeys, an initial LH rise was followed by a sharp fall. Later testing produced no LH pulse in response to kisspeptin-10, although NMDA and GnRH still produced LH pulses. The authors interpreted the pattern as GPR54 desensitisation. No other safety end points were reported in the abstract⁸.

Limitations of the evidence. The human studies were small physiological investigations and were not designed or powered to establish clinical outcomes or safety^{1,2,3,4,5,6,7}. The mutation study included only four patients and used one-tailed statistical tests⁶. Six studies were summarised from abstracts only, which limited assessment of methods and reporting^1,2,3,4,7,8. The comparison study in healthy men used inconsistent protocol labels for its LH AUC values; the values above were reproduced as stated in the abstract, with kisspeptin-10 and kisspeptin-54 identified separately⁵. The primate findings concerned three juvenile agonadal animals in a specific experimental model⁸. No dedicated reproductive-safety study was identified. None of the findings established efficacy or safety outside the described research models, and none of the cited papers characterised the Kisspeptin-10 product material.

References

1. George JT, Veldhuis JD, Roseweir AK, Newton CL, Faccenda E, Millar RP, Anderson RA (2011). Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men. The Journal of Clinical Endocrinology and Metabolism. PMID 21632807 DOI human study
2. Chan YM, Butler JP, Pinnell NE, Pralong FP, Crowley WF Jr, Ren C, Chan KK, Seminara SB (2011). Kisspeptin resets the hypothalamic GnRH clock in men. The Journal of Clinical Endocrinology and Metabolism. PMID 21470997 DOI human study
3. Jayasena CN, Nijher GM, Comninos AN, Abbara A, Januszewki A, Vaal ML, Sriskandarajah L, Murphy KG, Farzad Z, Ghatei MA, Bloom SR, Dhillo WS (2011). The effects of kisspeptin-10 on reproductive hormone release show sexual dimorphism in humans. The Journal of Clinical Endocrinology and Metabolism. PMID 21976724 DOI human study
4. George JT, Anderson RA, Millar RP (2012). Kisspeptin-10 stimulation of gonadotrophin secretion in women is modulated by sex steroid feedback. Human Reproduction. PMID 22956346 DOI human study
5. Jayasena CN, Abbara A, Narayanaswamy S, Comninos AN, Ratnasabapathy R, Bassett P, Mogford JT, Malik Z, Calley J, Ghatei MA, Bloom SR, Dhillo WS (2015). Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men. Human Reproduction. PMID 26089302 DOI human study
6. Young J, George JT, Tello JA, Francou B, Bouligand J, Guiochon-Mantel A, Brailly-Tabard S, Anderson RA, Millar RP (2013). Kisspeptin restores pulsatile LH secretion in patients with neurokinin B signaling deficiencies: physiological, pathophysiological and therapeutic implications. Neuroendocrinology. PMID 22377698 DOI human study
7. Yeung AC, Phylactou M, Koysombat K, Tsoutsouki J, Nyunt SW, Young M, Patel AH, Daniels E, Pierret ACS, Mills EG, Comninos AN, Abbara A, Dhillo WS (2026). Chronic subcutaneous kisspeptin-10 stimulates gonadotropin secretion for 12 days in healthy men. European Journal of Endocrinology. PMID 42549827 DOI human study
8. Seminara SB, Dipietro MJ, Ramaswamy S, Crowley WF Jr, Plant TM (2006). Continuous human metastin 45-54 infusion desensitizes G protein-coupled receptor 54-induced gonadotropin-releasing hormone release monitored indirectly in the juvenile male Rhesus monkey (Macaca mulatta): a finding with therapeutic implications. Endocrinology. PMID 16469799 DOI

This section summarises findings published in the cited peer-reviewed literature for informational purposes. It is not a claim of efficacy or safety, contains no dosing or administration information by design, and does not constitute medical, veterinary or scientific advice. Results in cell cultures or animal models do not predict effects in humans.