ECE2024 Oral Communications Oral Communications 1: Reproductive and Developmental Endocrinology (6 abstracts)
Kisspeptin as a test of hypothalamic function in women presenting with oligo / amenorrhoea
Bijal Patel 1 , Ali Abbara 1 , Arthur Yeung 1 , Maria Phylactou 1 , Jovanna Tsoutsouki 1 , Kanyada Koysombat 1 , Megan Young 1 , Sandhi Nyunt 1 , Ambreen Qayum 1 , Aaran Patel 1 , Agata Zielinska 1 , Yusra Omar 1 , Pei Eng 1 , Edouard G Mills 1 , Simon Hanassab 1 , Lisa Webber 1,2 , Channa Jayasena 1 , Tricia Tan 1 , Richard Quinton 3 , Sophie Clarke 4 , Alexander Comninos 1 & Waljit Dhillo 1
1Imperial College London, United Kingdom; 2Singapore General Hospital, Obstetrics and Gynaecology, Singapore, Singapore; 3Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom; 4University College London Hospitals Nhs Foundation Trust, United Kingdom
Background: Polycystic Ovary Syndrome (PCOS) and Functional Hypothalamic Amenorrhoea (FHA) are the two commonest causes of menstrual disturbance in pre-menopausal women. In practice, differentiating these two common reproductive disorders can be challenging. A fundamental abnormality that underpins both conditions is altered gonadotrophin releasing hormone (GnRH) pulsatility, being increased in PCOS but reduced in FHA. Likewise, congenital (e.g. congenital hypogonadotropic hypogonadism; CHH) and functional causes of hypogonadotropic hypogonadism (e.g. FHA) both have decreased hypothalamic function and can exhibit similar hormonal profiles presenting a diagnostic dilemma. Kisspeptin is a potent stimulator of hypothalamic GnRH secretion, and thus could be a novel tool to interrogate hypothalamic function in women presenting with menstrual disturbance.
Methods: Healthy women (n=33), women with PCOS (n=30), FHA (n=30), or CHH (n=8) aged 18-35 yrs not currently taking hormonal treatments, underwent two study visits to assess the hypothalamic response to an intravenous bolus of kisspeptin-54 (9.6 nmol/kg), and the pituitary response to GnRH (100 mg). Serum luteinising hormone (LH) and follicle stimulating hormone (FSH) were measured every 15 mins for 8 hrs. The maximal rise in LH and FSH from baseline was compared between the groups using an unpaired t test or Mann Whitney U test according to the distribution of the data. Receiver Operator Characteristic (ROC) analysis was used to assess the discriminatory potential of the hormonal response to kisspeptin and GnRH.
Results: The mean (SD) of the maximal rise in LH (IU/l) after kisspeptin was 9.7 (11.4) in healthy women, 9.7 (8.3) in women with PCOS, 17.6 (10.8) in women with FHA, and 1.0 (1.1) in women with CHH. The mean (SD) of the maximal rise in FSH (IU/l) after kisspeptin was 4.2 (3.4) in healthy women, 2.8 (2.1) in women with PCOS, 9.2 (5.6) in women with FHA, and 0.7 (0.5) in women with CHH. The maximal rise in FSH after kisspeptin could differentiate women with lean PCOS (BMI<25 kg/m2) from those with FHA (area under ROC 0.91, P=0.0001). The maximal rise in FSH after kisspeptin could differentiate women with FHA from women with CHH (auROC 1.00, P<0.0001), whereas the equivalent auROC for FSH rise after GnRH was 0.7 (P=0.086).
Conclusion: Kisspeptin offers a novel approach to assessing hypothalamic function in patients presenting with different reproductive disorders causing oligo/ amenorrhoea. Our data reveals for the first time that the hormonal response to kisspeptin has promising diagnostic potential to aid in the evaluation of women presenting with menstrual disturbance.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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