SFEBES2025 Poster Oral Presentations Reproductive Endocrinology (4 abstracts)
Gonadotropin response following intranasal kisspeptin administration is heightened in women with hypothalamic amenorrhoea compared to healthy women
Edouard G. Mills 1,2 , Jovanna Tsoutsouki 1 , Layla Thurston 1 , Maria Phylactou 1,2 , Bijal Patel 1 , Lisa Yang 1 , Sophie A. Clarke 1,2 , Megan Young 1 , Emma C. Alexander 1 , Sandhi Nyunt 1 , Arthur C. Yeung 1 , Muhammad Choudhury 1 , Anastasia Newman 1 , Paul Bech 1 , Ali Abbara 1,2 , Magda Swedrowska 3 , Ben Forbes 3 , Alexander N. Comninos 1,2 & Waljit S. Dhillo 1,2
1Section of Endocrinology and Investigative Medicine, Imperial College London, London, United Kingdom; 2Department of Endocrinology, Imperial College Healthcare NHS Trust, London, United Kingdom; 3Institute of Pharmaceutical Science, King’s College London, London, United Kingdom
Background: Kisspeptin administration by intravenous/subcutaneous routes activates hypothalamic GnRH neurons to stimulate reproductive hormones and is under rapid development for treating common reproductive disorders, including hypothalamic amenorrhoea (HA). However, these invasive routes limit patient acceptability. Intranasal offers a novel non-invasive delivery route, which would be clinically preferable. Herein, we compare the reproductive endocrine responses after intranasal kisspeptin administration in healthy women to women with HA.
Methods: Randomised, double-blinded, placebo-controlled, crossover study in 12 healthy women during the follicular phase (mean age 22.1±0.9yrs, BMI 22.1±0.8 kg/m2) and 10 women with HA (age 25.8±2.7yrs, BMI 19.9±1.3 kg/m2). After intranasal delivery of kisspeptin-54 (12.8nmol/kg) or 0.9%-saline (placebo), reproductive hormones were measured every 15minutes for 4hours. Mean±SEM presented.
Results: Intranasal kisspeptin-54 administration rapidly and robustly stimulated gonadotropin release in both cohorts. However, LH and FSH release were significantly augmented in women with HA, compared to healthy women: mean area under the curve (AUC) for the change in LH across 4hours 96.0±45.8h•IU/litre (healthy women) vs. 600.6±146.7h•IU/litre (women with HA) (P = 0.002). Consistently, mean AUC for the change in FSH was -36.1±23.4h•IU/litre (healthy women) vs. 474.9±237.3h•IU/litre (women with HA) (P = 0.02). The mean maximal LH change following kisspeptin-54 was >3fold greater in women with HA at 4.4±0.7IU/L vs. 1.4±0.3IU/L in healthy women (P < 0.001). Similarly, the mean maximal FSH change was >10-fold greater in women with HA at 3.1±1.3IU/L vs. 0.3±0.1IU/L in healthy women (P = 0.03).
Summary: Intranasal kisspeptin robustly stimulates reproductive hormone release in healthy women, with an even greater stimulation in women with HA. Therefore, intranasal kisspeptin offers not only a novel, effective, safe, and non-invasive route of administration for the management of reproductive disorders but also a potential simple diagnostic test to identify women with HA.
Volume 109
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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