SFEBES2021 Oral Communications Reproductive and Neuroendocrinology (6 abstracts)
Intranasal Kisspeptin Administration Stimulates Reproductive Hormone Secretion in Healthy Men
Edouard G Mills 1 , Magda Swedrowska 2 , Layla Thurston 1 , Maria Phylactou 1 , Bijal Patel 1 , Sophie A Clarke 1 , Lisa Yang 1 , Beatrice Muzi 1 , Muhammad Choudhry 1 , Emma Alexander 1 , Ali Abbara 1 , Ben Forbes 2 , Alexander N Comninos 1,3 & Waljit S Dhillo 1,3
1Imperial College London, London, United Kingdom; 2King’s College London, London, United Kingdom; 3Imperial College Healthcare NHS Trust, London, United Kingdom
Background: Kisspeptin is a critical activator of hypothalamic gonadotrophin-releasing hormone neurons, inducing release of downstream reproductive hormones. Intravenous or subcutaneous kisspeptin administration has been shown to have significant potential to treat reproductive disorders. However, intranasal administration could offer a novel non-invasive delivery route, which would be clinically preferable. We therefore sought to determine the effects of intranasal kisspeptin on reproductive hormone release in healthy men for the first time.
Methods: Randomised, double-blinded, placebo-controlled, cross-over study in 12 healthy men (mean age 28.3 years, BMI 24.5 kg/m2). After intranasal delivery of kisspeptin-54 (3.2, 6.4, 12.8 and 25.6 nmol/kg) or 0.9% saline, serum luteinising hormone (LH), follicle stimulating hormone (FSH) and testosterone were measured every 15-minutes for 4-h. Mean ± standard deviation are presented.
Results: Intranasal kisspeptin dose-dependently increased mean LH at doses from 3.2-12.8 nmol/kg (P = 0.008 and <0.0001 for 6.4 and 12.8 nmol/kg, respectively), with the maximal rises occurring 30-45 minutes post-administration. Correspondingly, the area under the LH curve was significantly elevated following all doses of kisspeptin compared to saline (3.2 nmol/kg: 172.2 ±222.6 h.IU/l [P =0.03]; 6.4 nmol/kg: 300.2 ±274.3 h.IU/l [P =0.002]; 12.8 nmol/kg: 595.7 ±340.4 h.IU/l [P =0.001]; 25.6 nmol/kg: 549.0 ±376.2 h.IU/l [P < 0.0001]). FSH levels followed a similar trajectory to LH in response to intranasal kisspeptin. Kisspeptin 12.8 nmol/kg significantly increased serum testosterone from 120-minutes onwards (P = 0.02), with a peak change from baseline of 5.5 ±5.5 nmol/l (P = 0.03).
Conclusion: We report the first investigation of the effects of intranasal kisspeptin delivery on reproductive hormone release in humans. Our results demonstrate that intranasal kisspeptin robustly and dose-dependently stimulates reproductive hormone release in healthy men. Given the ongoing development of kisspeptin therapeutics, intranasal kisspeptin delivery therefore offers a novel, effective and non-invasive administration route for the management of reproductive disorders.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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