Kisspeptin Administration Stimulates Reproductive Hormones but Does Not Affect Anxiety in Humans.

Mills EG, Thurston L, Yang L, Hunjan T, Phylactou M, Patel B, Clarke SA, Izzi-Engbeaya C, Tsoutsouki J, Young M, Bech P, Ertl N and 4 more

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Wall MB, Abbara A, Comninos AN, Dhillo WS

The Journal of clinical endocrinology and metabolism1 Oct 2025Cited by 2 (Europe PMC)

PMID40036336PMCIDPMC12527446DOI10.1210/clinem/dgaf128PepBankPUB-40036336

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Summary

ContextKisspeptin is a critical endogenous activator of the reproductive system, with escalating clinical interest as a novel therapeutic for common reproductive and psychosexual disorders. However, conflicting animal data suggest that kisspeptin can have anxiolytic, neutral, or anxiogenic effects.ObjectiveGiven the rapid development of kisspeptin-based therapeutics, it is important to comprehensively investigate the effects of kisspeptin administration on behavioral, biochemical, and physiological measures of anxiety in humans.MethodsNinety-five participants (N = 63 male, N = 32 female) completed a double-blind, randomized, placebo-controlled, crossover protocol (mean age ± SEM 30.9 ± 0.9 y, body mass index 24.0 ± 0.4), attending both for a 75-minute intravenous kisspeptin-54 infusion (1 nmol/kg/h) and rate-matched placebo (in random order). Behavioral, biochemical, and physiological measures of anxiety were compared between kisspeptin and placebo visits, using a state-anxiety psychometric questionnaire before and at the end of the infusions, and blood sampling (for reproductive hormones and cortisol) and heart rate measurements at 15-minute intervals. Blood pressure assessment took place before and at the end of the infusions.ResultsKisspeptin administration robustly increased serum luteinizing hormone to similar levels previously described using this administration protocol, confirming that the dose was biologically active (P < .001). State anxiety was not significantly altered by kisspeptin, compared to placebo (P = .13). Moreover, kisspeptin had no significant effects on circulating cortisol (P = .73), systolic (P = .74) or diastolic blood pressure (P = .90), or heart rate (P = .52).ConclusionThis is the first study demonstrating that a biologically active dose of kisspeptin to men and women does not affect behavioral, biochemical, or physiological measures of anxiety. Given that animal studies have yielded contradictory results, this provides key clinical data and reassurance that kisspeptin does not induce anxiety in humans and so informs the current development of kisspeptin-based therapeutics for common reproductive and psychosexual disorders.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

01HumanRandomized controlled trialEfficacy outcome
In healthy adults, intravenous kisspeptin‑54 increased serum luteinizing hormone versus placebo.
In plain wordsIn healthy adults, kisspeptin‑54 raised luteinizing hormone more than placebo.
Peptide
Kisspeptin-54 (metastin)
Outcome
IncreaseSerum luteinizing hormone
Study
n = 95
Comparator
Placebo
Outcome group
Sex hormones and fertility · Endocrine and hormones
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Source sentences
Summary
Kisspeptin administration robustly increased serum luteinizing hormone to similar levels previously described using this administration protocol, confirming that the dose was biologically active (P < .001).
1 context sentence(design, population, supporting numbers)
Summary · context
Ninety-five participants (N = 63 male, N = 32 female) completed a double-blind, randomized, placebo-controlled, crossover protocol (mean age ± SEM 30.9 ± 0.9 y, body mass index 24.0 ± 0.4), attending both for a 75-minute intravenous kisspeptin-54 infusion (1 nmol/kg/h) and rate-matched placebo (in random order).
Show in the study text Report a problemFND-4003633601
02HumanRandomized controlled trialEfficacy outcome
In healthy adults, kisspeptin‑54 did not significantly change state anxiety versus placebo.
In plain wordsIn healthy adults, kisspeptin‑54 did not change anxiety scores compared with placebo.
Peptide
Kisspeptin-54 (metastin)
Outcome
No significant changeState anxiety
Study
n = 95
Comparator
Placebo
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Source sentences
Summary
State anxiety was not significantly altered by kisspeptin, compared to placebo (P = .13).
1 context sentence(design, population, supporting numbers)
Summary · context
Ninety-five participants (N = 63 male, N = 32 female) completed a double-blind, randomized, placebo-controlled, crossover protocol (mean age ± SEM 30.9 ± 0.9 y, body mass index 24.0 ± 0.4), attending both for a 75-minute intravenous kisspeptin-54 infusion (1 nmol/kg/h) and rate-matched placebo (in random order).
Show in the study text Report a problemFND-4003633602
03HumanRandomized controlled trialEfficacy outcome
In healthy adults, kisspeptin‑54 had no significant effect on circulating cortisol versus placebo.
In plain wordsIn healthy adults, kisspeptin‑54 did not change cortisol compared with placebo.
Peptide
Kisspeptin-54 (metastin)
Outcome
No significant changeCirculating cortisol
Study
n = 95
Comparator
Placebo
Outcome group
Anxiety and mood · Endocrine and hormones
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Source sentences
Summary
Moreover, kisspeptin had no significant effects on circulating cortisol (P = .73), systolic (P = .74) or diastolic blood pressure (P = .90), or heart rate (P = .52).
1 context sentence(design, population, supporting numbers)
Summary · context
Ninety-five participants (N = 63 male, N = 32 female) completed a double-blind, randomized, placebo-controlled, crossover protocol (mean age ± SEM 30.9 ± 0.9 y, body mass index 24.0 ± 0.4), attending both for a 75-minute intravenous kisspeptin-54 infusion (1 nmol/kg/h) and rate-matched placebo (in random order).
Show in the study text Report a problemFND-4003633603
04HumanRandomized controlled trialEfficacy outcome
In healthy adults, kisspeptin‑54 had no significant effect on systolic blood pressure versus placebo.
In plain wordsIn healthy adults, kisspeptin‑54 did not change systolic blood pressure compared with placebo.
Peptide
Kisspeptin-54 (metastin)
Outcome
No significant changeSystolic blood pressure
Study
n = 95
Comparator
Placebo
Outcome group
Blood pressure · Cardiovascular
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Source sentences
Summary
Moreover, kisspeptin had no significant effects on circulating cortisol (P = .73), systolic (P = .74) or diastolic blood pressure (P = .90), or heart rate (P = .52).
1 context sentence(design, population, supporting numbers)
Summary · context
Ninety-five participants (N = 63 male, N = 32 female) completed a double-blind, randomized, placebo-controlled, crossover protocol (mean age ± SEM 30.9 ± 0.9 y, body mass index 24.0 ± 0.4), attending both for a 75-minute intravenous kisspeptin-54 infusion (1 nmol/kg/h) and rate-matched placebo (in random order).
Show in the study text Report a problemFND-4003633604
05HumanRandomized controlled trialEfficacy outcome
In healthy adults, kisspeptin‑54 had no significant effect on diastolic blood pressure versus placebo.
In plain wordsIn healthy adults, kisspeptin‑54 did not change diastolic blood pressure compared with placebo.
Peptide
Kisspeptin-54 (metastin)
Outcome
No significant changeDiastolic blood pressure
Study
n = 95
Comparator
Placebo
Outcome group
Blood pressure · Cardiovascular
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Measurements
P value
0.9
diastolic blood pressure
Source sentences
Summary
Moreover, kisspeptin had no significant effects on circulating cortisol (P = .73), systolic (P = .74) or diastolic blood pressure (P = .90), or heart rate (P = .52).
1 context sentence(design, population, supporting numbers)
Summary · context
Ninety-five participants (N = 63 male, N = 32 female) completed a double-blind, randomized, placebo-controlled, crossover protocol (mean age ± SEM 30.9 ± 0.9 y, body mass index 24.0 ± 0.4), attending both for a 75-minute intravenous kisspeptin-54 infusion (1 nmol/kg/h) and rate-matched placebo (in random order).
Show in the study text Report a problemFND-4003633605
06HumanRandomized controlled trialEfficacy outcome
In healthy adults, kisspeptin‑54 had no significant effect on heart rate versus placebo.
In plain wordsIn healthy adults, kisspeptin‑54 did not change heart rate compared with placebo.
Peptide
Kisspeptin-54 (metastin)
Outcome
No significant changeHeart rate
Study
n = 95
Comparator
Placebo
Outcome group
Heart function · Cardiovascular
Studied dose
1 nmol/kg/h · intravenous · 75 minutesAs given in this study (human).
Source sentences
Summary
Moreover, kisspeptin had no significant effects on circulating cortisol (P = .73), systolic (P = .74) or diastolic blood pressure (P = .90), or heart rate (P = .52).
1 context sentence(design, population, supporting numbers)
Summary · context
Ninety-five participants (N = 63 male, N = 32 female) completed a double-blind, randomized, placebo-controlled, crossover protocol (mean age ± SEM 30.9 ± 0.9 y, body mass index 24.0 ± 0.4), attending both for a 75-minute intravenous kisspeptin-54 infusion (1 nmol/kg/h) and rate-matched placebo (in random order).
Show in the study text Report a problemFND-4003633606

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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