ECE2022 Poster Presentations Reproductive and Developmental Endocrinology (61 abstracts)
Intranasal kisspeptin administration stimulates reproductive hormone secretion in healthy volunteers and patients with hypogonadism
Edouard Mills 1 , Magda Swedrowska 2 , Layla Thurston 1 , Maria Phylactou 1 , Bijal Patel 1 , Lisa Yang 1 , Sophie Clarke 1 , Beatrice Muzi 1 , Emma Alexander 1 , Muhammad Choudhury 1 , Paul Bech 1 , Ali Abbara 1 , Ben Forbes 2 , Alexander Comninos 1 & Waljit Dhillo 1
1Imperial College London, Hammersmith Campus, Section of Endocrinology and Investigative Medicine, London, United Kingdom; 2King’s College London, Institute of Pharmaceutical Science, London, United Kingdom
Background: Kisspeptin is a critical activator of hypothalamic gonadotrophin releasing hormone (GnRH) neurons and has significant potential to treat common reproductive disorders. To date, kisspeptin has solely been administered to humans via the intravenous or subcutaneous routes, however intranasal administration could offer a novel non-invasive delivery route. We therefore sought to determine the effects of intranasal kisspeptin on reproductive hormone release in humans for the first time.
Methods: Randomised, double-blinded, placebo-controlled, cross-over study in 12 healthy men (mean±SEM age 28.3±1.7 years; BMI 24.5±0.7 kg/m2). After monitored self-administration of intranasal kisspeptin-54 (3.2, 6.4, 12.8 and 25.6 nmol/kg) or 0.9% saline, serum reproductive hormone levels were measured every 15 minutes for four h. Subsequently, four women (mean age 29.8±3.7 years; BMI 21.2±1.1 kg/m2) with hypothalamic amenorrhoea (HA) attended for the same protocol comparing intranasal kisspeptin-54 (12.8 nmol/kg) and 0.9% saline. Mean±SEM was presented. Time profiles of hormone levels were compared using two-way ANOVA, and multiple means using one-way ANOVA.
Results: In healthy men, intranasal kisspeptin dose-dependently increased mean luteinising hormone (LH) levels at doses between 3.2-12.8 nmol/kg (P=0.008 and <0.0001 for 6.4 and 12.8 nmol/kg vs saline, respectively), with the maximal rises occurring 30-45 minutes post-administration. The maximal LH change from baseline was significantly elevated following all kisspeptin doses vs saline (saline: 1.54±0.30 IU/l; 3.2 nmol/kg: 2.46±0.30 IU/l [p=0.01]; 6.4 nmol/kg: 3.08±0.48 IU/l [p=0.04]; 12.8 nmol/kg: 4.45±0.59 IU/l [p=0.002]; 25.6 nmol/kg: 4.07±0.66 IU/l [p=0.003]). Follicle stimulating hormone (FSH) levels followed a similar trajectory to LH. Kisspeptin at 12.8 nmol/kg increased serum testosterone from 120 minutes onwards (P=0.02), with a maximal change from baseline of 4.9±0.7 nmol/l (P=0.03). In women with HA, intranasal kisspeptin increased mean LH (P=0.002 vs saline), with the peak levels occurring 30-45 minutes post-administration. The maximal LH change from baseline was 4.06±0.89 IU/l, compared with 0.20±0.38 IU/l for saline (P=0.03). Intranasal kisspeptin increased mean FSH (P=0.01 vs saline). No significant changes in downstream serum oestradiol or progesterone were observed during the acute four-h study.
Conclusion: We report the first investigation of the effects of intranasal kisspeptin delivery on reproductive hormone release. Our results demonstrate that intranasal kisspeptin robustly and dose-dependently stimulates reproductive hormone release in healthy men and in a patient-group of women with hypogonadism. Given the ongoing development of kisspeptin therapeutics, intranasal kisspeptin offers a novel, safe, effective and non-invasive route of administration for the management of reproductive disorders that would be preferred by patients and clinicians alike.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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