Kisspeptin and LH pulsatility in patients with functional hypothalamic amenorrhea
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ORIGINAL ARTICLE
Kisspeptin and LH pulsatility in patients with functional hypothalamic amenorrhea Agnieszka Podfigurna1 Marzena Maciejewska-Jeske1 Blazej Meczekalski1 Alessandro D. Genazzani2 ●
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Received: 18 May 2020 / Accepted: 26 August 2020 © The Author(s) 2020
Abstract Purpose Functional hypothalamic amenorrhea (FHA) occurs in response to exaggerated stressors with or without body weight loss. Various hormones, neurotransmitters, and neuromodulators are involved in the control of GnRH and kisspeptin is one of them. Our study aimed to evaluate the putative temporal coupling between kisspeptin and GnRH-induced LH pulsatile secretion. Methods In total, 71 patients with FHA were selected for this study. All patients undergo to a pulsatility study for LH and kisspeptin evaluation (120 min, sampling every 10 min), and to an endocrine evaluation for prolactin (PRL), estradiol (E2), androstenedione (A), 17-hydroxy-progesterone (17OHP), TSH, fT3, fT4, insulin, cortisol and testosterone (T), glucose, total cholesterol, triglycerides. Results Our data demonstrated kisspeptin and LH pulsatile secretions and that both hormones are co-secreted and temporally coupled at time 0 (p < 0.05). When patients were subdivided in hypo-LH (≤3 mIU/ml, n = 58) and normo-LH (>3 mIU/ml, n = 13), more insights were observed on the specific correlations of metabolic and hormone profiles with pulsatility indexes of LH and kisspeptin. Conclusions Our study demonstrated the presence of a distinct kisspeptin episodic secretion in patients with FHA, and showed the temporally coupling of kisspeptin with LH secretory episodes thus supporting that though in amenorrhea, the reproductive axis is still relying on kisspeptin to drive GnRH discharge. In addition, correlations among hormonal data sustain the hypothesis that stress-induced compensatory events are the main direct and indirect promoters of the reproductive blockade in patients affected by FHA. Keywords Kisspeptin LH Pulses Functional hypothalamic amenorrhea ●
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Introduction Secondary amenorrhea is a quite frequent clinical occurrence and when no endocrine or systemic factors are recognized as casual factors, it is usually identified as a hypothalamic blockade. Typically, such hypothalamic dysfunction occurs in all women during fertile life, with no difference between adolescence as well as during adult life [1, 2] and it is
* Blazej Meczekalski [email protected] 1
Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland
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Department of Obstetrics and Gynecology, Gynecological Endocrinology Center, University of Modena and Reggio Emilia, Modena, Italy
considered as functional hypothalamic amenorrhea (FHA). FHA occurs in response to exaggerated metabolic, physical, or psychological stress (after severe dieting, heavy training, intense emotional events, or a combination of them) with or without body weight loss [3–6]. These physical, psychological, and metabolic stressors negatively affect gonadot
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