SFEBES2026 Oral Communications Bone and Reproductive Endocrinology (6 abstracts)
Kisspeptin challenge test reveals hypothalamic dysfunction in obesity-related hypogonadism
Kanyada Koysombat 1,2 , Patrick McGown 1,2 , Arthur C Yeung 1 , Agathoklis Efthymiadis 1,2 , Sandhi W Nyunt 1,2 , Maria Phylactou 1,2 , Megan Young 1,2 , Bijal Patel 1,2 , Elisabeth Daniels 1,2 , Aureliane Pierret 1,2 , Aaran H Patel 1,2 , Jovanna Tsoutsouki 1,2 , Edouard G Mills 1,2 , Anna M Kowalka 1 , Chioma Izzi-Engbeaya 1,2 , Tricia M-M Tan 1,2 , Alexander N Comninos 1,2 , Ali Abbara 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
Background: Male obesity-related secondary hypogonadism (MOSH) affects two-thirds of men with BMI ≥ 40 kg/m2 and is associated with increased morbidity and mortality. Animal models suggest decreased hypothalamic function in obesity-related hypogonadism. Herein, we use kisspeptin for the first time to examine hypothalamic dysfunction in men with obesity, both with and without hypogonadism.
Methods: Men with MOSH (BMI ≥30 kg/m2; n = 21) were identified by fasting total-testosterone <10nmol/l (SfE guidelines). We also enrolled healthy eugonadal controls both with (BMI ≥30kg/m2, n = 20) and without obesity (BMI <30kg/m2, n = 80). Endocrine profiling included LH-pulsatility assessment (10-minutely sampling for 8hrs), responses to intravenous kisspeptin and gonadotrophin-releasing hormone (GnRH) bolus to interrogate hypothalamic and pituitary function, respectively. Hormone concentrations were compared using Kruskal-Wallis test, and temporal endocrine profiles using mixed-effects models.
Results: Total-testosterone (β = -0.47), free-testosterone (β = -0.01), and dihydrotestosterone (β = -0.04) were inversely associated with BMI (all P <0.0001). LH pulse-frequency [median, IQR] was increased with obesity (BMI 20–30kg/m2: 3.00 [3.00,4.75] vs >40kg/m2: 5.00 [4.00,6.00]) pulses per 8hrs; P = 0.007, but LH pulse-amplitude and GnRH responses did not differ. The early-phase LH response to kisspeptin was blunted in men with MOSH (median area-under-the-curve at 60mins: MOSH 38.78 [23.85, 78.26] vs lean controls 108.7 [78.56, 190.40] p<0.0001, vs eugonadal men with obesity 124.1 [81.58, 163.90] IU•h/l, P = 0.0011). FSH responses to kisspeptin were higher in eugonadal men with obesity than lean controls (893.80 [596.10, 1104.00] vs 434.80 [292.70, 692.10] IU•h/l; P = 0.003).
Conclusion: Our data revealed increased LH pulse-frequency but no change in pulse-amplitude in men with obesity. Eugonadal men with obesity had an increased response to kisspeptin, but the early phase response to kisspeptin was reduced in men with MOSH. Our data demonstrates, for the first time in humans, that abnormal hypothalamic function plays a key role in the pathophysiology of obesity-related hypogonadism.
Volume 117
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Endocrine Abstracts
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