Key papers ✓ 6~ 4

• ✓ Positive human RCTEur J Endocrinol · 2026

  Chronic subcutaneous kisspeptin-10 stimulates gonadotropin secretion for 12 days in healthy men.

  Humans15 peopleRandomizedPlacebo-controlledUp to 12 days

  Randomized, single-blinded, placebo-controlled study of subcutaneous kisspeptin-10: acute dose-response, 5-day continuous, 12-day intermittent (8 h on, 16 h off)

  15 healthy men (12 controls), single-blind placebo-controlled: subcutaneous kisspeptin-10 dose-dependently raised LH, FSH and testosterone; with continuous 5-day infusion gonadotropins returned to vehicle levels (testosterone stayed raised), while daily 8-hour infusions sustained LH rises for 12 days.

  Key resultDaily 8 h infusions over 12 days sustained gonadotropin rises (mean LH increase: vehicle -0.16 ± 0.19; day 1 +1.68 ± 0.25; day 12 +1.14 ± 0.33, P = .003 vs vehicle); continuous 5-day infusion did not sustain gonadotropins

  Study details

  Studied

  Healthy men

  Compared with

  Vehicle

  Main outcome

  LH, FSH and testosterone

  Sample

  15 healthy men (study 1: 7, study 2: 4, study 3: 7); 12 men served as controls

  Authors' conclusion

  Chronic subcutaneous kisspeptin-10 sustains gonadotropin and testosterone secretion in healthy men for 12 days and can inform chronic protocols for reproductive disorders.

  Limitations

  Small groups.

  DOI 10.1093/ejendo/lvag134PubMed 42549827
• ✓ Positive human RCTJ Clin Endocrinol Metab · 2016

  Interactions Between Neurokinin B and Kisspeptin in Mediating Estrogen Feedback in Healthy Women.

  Humans10 peopleRandomizedSham/vehicle control7-hour infusion

  Two-way crossover of kisspeptin-10 vs vehicle infusion during estradiol, with NK3R antagonist (AZD4901) pretreatment

  Healthy women, randomized crossover: a 7-hour kisspeptin-10 infusion increased LH secretion during the estrogen-inhibitory phase; the study mainly examined interaction with neurokinin B signaling.

  Key resultNK3R antagonist decreased LH pulse frequency (0.5 ± 0.2 vs 0.7 ± 0.2 pulses/h, P < .05); LH at 48 hours was lower (7.5 ± 4.8 vs 15.0 ± 11.4 IU/L, P < .05)

  Study details

  Studied

  Healthy women with regular menses

  Compared with

  Vehicle infusion; no-treatment controls

  Main outcome

  Plasma gonadotropin secretion

  Sample

  10 women on NK3R antagonist, with 10 no-treatment controls

  Authors' conclusion

  NKB signaling regulates GnRH/LH secretion in normal women, predominantly proximal to kisspeptin in mediating estrogenic positive and negative feedback.

  Limitations

  Small sample.

  DOI 10.1210/jc.2016-2132PubMed 27636018Free full text
  Figure 3. Figure 2.
• ~ Mixed human trialHum Reprod · 2012

  Kisspeptin-10 stimulation of gonadotrophin secretion in women is modulated by sex steroid feedback.

  Humanssize not reported60 minutes of sampling

  Experimental study of IV kisspeptin-10 (0.3 µg/kg) bolus

  IV kisspeptin-10 (0.3 µg/kg) raised LH in follicular-phase women, postmenopausal women and progestogen users, but not in women on the combined pill; FSH rose only in postmenopausal women.

  Key resultLH ΔAUC: follicular 2.3 ± 0.8 IU/l h (P = 0.009), post-menopausal 5.3 ± 0.9 (P 0.002), combined pill 0.9 ± 0.4 (P 0.13, not significant)

  Study details

  Studied

  Women in early follicular phase, post-menopausal women, and women on sex-steroid contraceptives

  Compared with

  Between sex-steroid milieus

  Main outcome

  LH and FSH area under the curve

  Sample

  Follicular-phase women, 6 post-menopausal women, and 8 women on contraceptives (combined pill 4, progestogen implants 4)

  Authors' conclusion

  Kisspeptin-10 stimulates gonadotrophin secretion in women, and the pituitary gonadotrope appears to be an important locus of estrogen feedback.

  Limitations

  Only acute responses to a single IV bolus assessed.

  DOI 10.1093/humrep/des326PubMed 22956346
• ~ Mixed human trialAndrologia · 2019

  Age-dependent changes in the reproductive axis responsiveness to kisspeptin-10 administration in healthy men.

  Humanssize not reported30 min before to 120 min after injection

  Single IV bolus of kisspeptin-10 (1 µg/kg) with serial sampling

  Single IV bolus (1 µg/kg) in healthy young, middle-aged and older men: LH rose in all groups, but testosterone rose significantly only in the younger adult group.

  Key resultLH rose significantly (p < 0.05) in all groups; testosterone rose significantly (p < 0.05) only in the adult group

  Study details

  Studied

  Healthy adult, middle-aged and older men

  Compared with

  Pre-injection baseline across age groups

  Main outcome

  Plasma LH and testosterone

  Authors' conclusion

  The central hypothalamic-pituitary axis stays responsive to kisspeptin across life, but Leydig cell responsiveness to kisspeptin-induced LH decreases with age.

  Limitations

  Sample size not stated in the abstract.

  DOI 10.1111/and.13219PubMed 30590872
• ✓ Positive animalProc Natl Acad Sci U S A · 2005

  Increased hypothalamic GPR54 signaling: a potential mechanism for initiation of puberty in primates.

  Animalssize not reported

  Kisspeptin-10 injection with LH measurement; hypothalamic KiSS-1 and GPR54 mRNA expression

  In juvenile male monkeys, IV or intracerebroventricular kisspeptin-10 triggered robust GnRH-driven LH release, abolished by a GnRH-receptor antagonist.

  Key resultHypothalamic GPR54 mRNA increased approximately 3-fold from juvenile to midpubertal stage in intact females

  Study details

  Studied

  Agonadal juvenile male monkeys and peripubertal monkeys

  Compared with

  GnRH-receptor antagonist pretreatment

  Main outcome

  LH secretion (GnRH release); KiSS-1 and GPR54 mRNA

  Authors' conclusion

  GPR54 signaling in the primate hypothalamus may be activated at the end of the juvenile phase and contribute to pubertal resurgence of pulsatile GnRH release.

  Limitations

  Monkey study.

  DOI 10.1073/pnas.0409822102PubMed 15684075Free full text
• ✓ Positive animalHorm Metab Res · 2014

  Primate HPT axis response to the peripheral kisspeptin challenge under different time periods of food restriction in monkeys.

  Animals5 animalsSham/vehicle control3-hour post-injection period

  IV boluses of vehicle and human kisspeptin-10 (50 μg) in each condition

  In adult male rhesus monkeys, IV kisspeptin-10 stimulated testosterone in fed and fasted states, but the response was smaller and slower after 18-24 hours of fasting.

  Key resultMean testosterone in the 3-h post-KP10 period was significantly lower in 18- and 24-h fasted monkeys than in 12-h fasted and fed monkeys (p<0.01)

  Study details

  Studied

  Adult male rhesus monkeys fasted 12, 18 or 24 h, or fed ad libitum

  Compared with

  Fed and vehicle conditions

  Main outcome

  Testosterone response

  Sample

  5 sexually mature male rhesus monkeys

  Authors' conclusion

  18- and 24-h fasting suppressed the testosterone response to kisspeptin in onset and amount, which may partly involve attenuated responsiveness to endogenous kisspeptin.

  Limitations

  Five monkeys.

  DOI 10.1055/s-0033-1363263PubMed 24500987
• ✓ Positive human trialJ Clin Endocrinol Metab · 2011

  Kisspeptin-10 is a potent stimulator of LH and increases pulse frequency in men.

  Humanssize not reportedSham/vehicle controlUp to 22.5 h infusion

  Dose-response of IV bolus kisspeptin-10 vs vehicle, then infusion for up to 22.5 h

  First kisspeptin-10 study in men: IV boluses of kisspeptin-10 raised LH dose-dependently (peak 1 microgram/kg, LH 4.1 to 12.4 IU/L), and infusion raised testosterone, LH pulse frequency and pulse size.

  Key resultAt 30 min, LH rose from 4.1 +/- 0.4 to 12.4 +/- 1.7 IU/liter (P < 0.001, n = 6) at 1 microgram/kg; 22.5-h infusion raised testosterone from 16.6 to 24.0 nmol/liter (P < 0.001).

  Study details

  Studied

  Healthy men

  Compared with

  Vehicle

  Main outcome

  LH concentration, pulse frequency and testosterone

  Authors' conclusion

  Kisspeptin-10 boluses potently evoke LH secretion in men and continuous infusion increases testosterone, LH pulse frequency and size; analogues have therapeutic potential.

  Limitations

  Very small groups (n = 4-6 per experiment).

  DOI 10.1210/jc.2011-0089PubMed 21632807Free full text
• ✓ Positive human trialClin Endocrinol (Oxf) · 2013

  Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism.

  Humans12 peopleNo control group

  Proof-of-concept physiology study, bolus and 11 h infusion

  Proof-of-concept in 5 men with type 2 diabetes and low testosterone: IV kisspeptin-10 raised LH, LH pulse frequency and testosterone (8.5 to 11.4 nmol/L during infusion); healthy men responded similarly.

  Key resultInfusion raised LH from 3.9 to 20.7 IU/l (P = 0.03) and testosterone from 8.5 to 11.4 nmol/l (P = 0.002).

  Study details

  Studied

  Hypotestosteronaemic men with type 2 diabetes; healthy men

  Main outcome

  LH and testosterone

  Sample

  5 men with type 2 diabetes and low testosterone plus 7 age-matched healthy men

  Authors' conclusion

  Kisspeptin-10 increased LH pulse frequency and secretion and testosterone in men with T2DM; suggests a possible role for kisspeptin agonists in central hypogonadism.

  Limitations

  Five patients, uncontrolled infusion experiment.

  DOI 10.1111/cen.12103PubMed 23153270
• ~ Mixed human trialHum Reprod · 2015

  Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men.

  Humanssize not reportedPlacebo-controlled3 h infusions on separate study days

  Single-blinded placebo-controlled physiological study of kisspeptin-10, kisspeptin-54 and GnRH

  Five men per dose group: IV kisspeptin-10 and kisspeptin-54 raised LH and FSH similarly but GnRH was about 3-fold more potent than kisspeptin-10; small single-blinded study.

  Key resultMean LH AUC 10.81 +/- 1.73 h.IU/l (kisspeptin-10), 14.43 +/- 1.27 (kisspeptin-54), 34.06 +/- 5.18 (GnRH) at 1.0 nmol/kg/h.

  Study details

  Studied

  Healthy men, 5 per dosing group

  Compared with

  Vehicle and GnRH

  Main outcome

  Serum LH and FSH

  Authors' conclusion

  The two kisspeptin isoforms gave similar gonadotrophin secretion at the doses tested; GnRH was more potent than either.

  Limitations

  Small sample size, as the authors note.

  DOI 10.1093/humrep/dev143PubMed 26089302Free full text
  Figure 3 Figure 4
• ~ Mixed human trialHormones (Athens) · 2026

  Dynamic modulation of LH secretion by continuous kisspeptin infusion in healthy men.

  Humans3 peopleNo control group24 hours

  Uncontrolled physiological study of continuous intravenous kisspeptin-10

  Three healthy men on a 24-hour continuous kisspeptin-10 infusion: LH rose 5-8 fold then declined 13-47% from peak by end of infusion, suggesting partial attenuation; FSH and testosterone rose modestly.

  Key resultLH rose from 2.8-3.8 to 17.5-30.6 mIU/mL, then fell 13-47% from maximum to end of infusion.

  Study details

  Studied

  Healthy adult men

  Main outcome

  LH, FSH, testosterone

  Sample

  3 healthy men

  Authors' conclusion

  Continuous kisspeptin infusion is a complementary physiologic tool for studying GnRH-induced LH secretion; further studies are needed on receptor response to non-pulsatile ligand.

  Limitations

  Only 3 participants, no control.

  DOI 10.1007/s42000-026-00795-yPubMed 42230485Free full text

Reported side effects

The kisspeptin-10 study abstracts report hormone responses but no adverse-event data; longer-term human safety is unstudied.

22 registered human trials (5 active)

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.