Kisspeptin Administration Stimulates Reproductive Hormones But Does Not Affect Anxiety in Humans

Background: Kisspeptin 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. Given the rapid development of kisspeptin-based therapeutics, it is important to comprehensively investigate kisspeptin's effects on anxiety in humans.

Methods: Ninety-five participants (N=63 male, N=32 female) completed a double-blind, randomized, placebo-controlled, crossover protocol (mean age±SEM 30.9±0.9yrs, BMI 24.0±0.4kg/m2), attending for both a 75-minute intravenous kisspeptin-54 infusion (1nmol/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.

Results: Kisspeptin administration robustly increased serum LH to similar levels previously described using this administration protocol, confirming that the dose was biologically active (P<0.001). State anxiety was not significantly altered by kisspeptin, compared to placebo (P=0.13). Moreover, kisspeptin had no significant effects on circulating cortisol (P=0.73), systolic (P=0.74) or diastolic blood pressure (P=0.90), or heart rate (P=0.52).