ECEESPE2025 Oral Communications Oral Communications 5: Reproductive and Developmental Endocrinology Part 1 (5 abstracts)
Gonadotropin rise 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 Clarke 1,2 , Megan Young 1 , Emma Alexander 1 , Sandhi Nyunt 1 , Arthur Yeung 1 , Muhammad Choudhury 1 , Anastasia Newman 1 , Paul Bech 1 , Ali Abbara 1,2 , Magda Swedrowska 3 , Ben Forbes 3 , Alexander Comninos 1,2 & Waljit Dhillo 1,2
1Imperial College London, Section of Endocrinology and Investigative Medicine, London, United Kingdom; 2Imperial College Healthcare NHS Trust, Department of Endocrinology, London, United Kingdom; 3King’s College London, Institute of Pharmaceutical Science, London, United Kingdom
JOINT650
Background: Kisspeptin administration by intravenous or subcutaneous routes activates hypothalamic GnRH neurons to stimulate downstream reproductive hormone release and is under rapid development for treating common reproductive disorders, including hypothalamic amenorrhoea (HA). However, these invasive routes limit patient acceptability and clinical use. Intranasal offers a novel non-invasive delivery route, which would be clinically preferable to patients and clinicians. Herein, we compare the reproductive endocrine responses following intranasal kisspeptin administration in healthy women to women with HA.
Methods: Randomised, double-blinded, placebo-controlled, crossover study in 12 healthy (ovulatory) women during the follicular phase (mean age±SEM 22.1±0.9 yrs, BMI 22.1±0.8 kg/m2) and 10 women with HA (age 25.8±2.7 yrs, BMI 19.9±1.3 kg/m2). After intranasal administration of kisspeptin-54 (12.8 nmol/kg) or 0.9% saline (placebo), reproductive hormones were measured every 15 minutes for 4 hours. Groups were compared by unpaired t-tests.
Results: Intranasal kisspeptin-54 administration rapidly and robustly stimulated gonadotropin release in both study groups, without any side effects or adverse events encountered. 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 4 hours 96.0±45.8 h·IU/litre (healthy women) vs. 600.6±146.7 h·IU/litre (women with HA) (P=0.002). Consistently, mean AUC for the change in FSH was -36.1±23.4 h·IU/litre (healthy women) vs. 474.9±237.3 h·IU/litre (women with HA) (P=0.02). The mean maximal increase in LH following kisspeptin-54 was over three-fold greater in women with HA at 4.4±0.2 IU/l vs. 1.4±0.3 IU/l in healthy women (P <0.001). Similarly, the mean maximal increase in FSH was over ten-fold greater in women with HA at 3.1±0.3 IU/l vs. 0.3±0.1 IU/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 interrogate hypothalamic function and identify women with HA.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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