Evidence map›Paper›PMID 40036336›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2025

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

Edouard G Mills, Layla Thurston, Lisa Yang, Tia Hunjan, Maria Phylactou, Bijal Patel, Sophie A Clarke, Chioma Izzi-Engbeaya, Jovanna Tsoutsouki, Megan Young and 6 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Edouard G MillsSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.ORCID 0000-0002-8937-6463
Layla ThurstonSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Lisa YangSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Tia HunjanSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Maria PhylactouSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.ORCID 0000-0002-0464-5768
Bijal PatelSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Sophie A ClarkeSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Chioma Izzi-EngbeayaSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.ORCID 0000-0001-7599-0166
Jovanna TsoutsoukiSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Megan YoungSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Paul BechSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Natalie ErtlSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Matthew B WallSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.
Ali AbbaraSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.ORCID 0000-0003-2795-5256
Alexander N ComninosSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.ORCID 0000-0002-7104-2297
Waljit S DhilloSection of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.ORCID 0000-0001-5950-4316

Funding

Department of HealthMRCMRC Clinical Research Training Fellowships MR/R000484/1MRC Clinical Research Training Fellowships MR/W024144/1NHSNIHRNIHR Academic Clinical LectureshipsNIHR Clinical Research NetworkNIHR Imperial Biomedical Research CentreNIHR Imperial Clinical Research Facility
6 · The paper itself

Abstract

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.

Indexed as

AnxietyKisspeptinsAdultCross-Over StudiesDouble-Blind MethodFemaleHeart RateHumansHydrocortisoneLuteinizing HormoneMaleYoung AdultHydrocortisoneKISS1 protein, humanKisspeptinsLuteinizing Hormoneanxietybehaviorkisspeptinreproduction

Identifiers

PMID40036336
PMCPMC12527446

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.