SFEIES24 Poster Presentations Neuroendocrinology (30 abstracts)
Kisspeptin does not induce anxiety in humans
Edouard G. Mills 1,2 , Layla Thurston 1 , Lisa Yang 1 , Sofiya Suladze 1 , Tia Hunjan 1 , Maria Phylactou 1,2 , Bijal Patel 1 , Sophie A. Clarke 1,2 , Amar J. Shah 1 , Chioma Izzi-Engbeaya 1,2 , Jovanna Tsoutsouki 1 , Megan Young 1 , Paul Bech 1 , Natalie Ertl 1,3 , Lysia Demetriou 1,3 , Matthew B. Wall 1,3 , David Goldmeier 2 , Ali Abbara 1,2 , Alexander N. Comninos 1,2 & Waljit S. Dhillo 1,2
1Imperial College London, London, United Kingdom; 2Imperial College Healthcare NHS Trust, London, United Kingdom; 3Invicro London, London, United Kingdom
Background: The neuropeptide kisspeptin is a critical endogenous activator of the reproductive system, with escalating clinical interest as a novel therapeutic agent for reproductive and psychosexual disorders. However, conflicting animal data suggest that kisspeptin can have anxiolytic, neutral, or anxiogenic effects. Given the rapid development of kisspeptin-based therapeutics, it is important to clarify kisspeptin’s effects on psychometric measures of anxiety and associated circulating cortisol levels in humans.
Methods: Ninety-five eugonadal participants (n = 63 men, n = 32 premenopausal women) completed a double-blind, randomised, placebo-controlled, crossover study (mean age ±SEM 30.9±0.9yrs, BMI 24.0±0.4kg/m 2). Participants attended for a 75minute intravenous kisspeptin-54 infusion (1nmol/kg/h) and again for a rate-matched placebo. Blood was sampled at 15-minute intervals throughout the infusions for circulating kisspeptin, LH, sex-steroid levels, and cortisol. Participants completed a state anxiety questionnaire (‘STAI Y1-State’) before and at the end of the infusions to assess for any dynamic effects of the infusions on anxiety.
Results: Intravenous kisspeptin significantly increased serum LH to similar levels previously described using this administration protocol, confirming that the dose was biologically active (P < 0.001). As expected, kisspeptin had no significant effects on downstream sex-steroid levels during the 75minute study period, thereby excluding these as possible confounders. State anxiety was not significantly altered by kisspeptin, compared to placebo (mean difference in ‘STAI Y1-State’ scores during the infusions: kisspeptin -0.4±0.8, placebo 1.3±0.8, P = 0.09). Moreover, kisspeptin had no significant effects on circulating cortisol compared to placebo (P = 0.73).
Summary: This is the largest study demonstrating that a biologically active dose of kisspeptin to humans does not affect psychometric measures of anxiety and associated cortisol levels. Given that animal studies have yielded conflicting results, this provides important clinical data and reassurance that kisspeptin does not induce anxiety in humans and so informs the rapid development of kisspeptin-based therapeutics for reproductive and psychosexual disorders.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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