Kisspeptin in functional hypothalamic amenorrhea: Pathophysiology and therapeutic potential.

Autor: Patel AH; Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK.; Department of Endocrinology, Chelsea and Westminster Hospital, London, UK., Koysombat K; Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK.; Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK., Pierret A; Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK., Young M; Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK., Comninos AN; Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK.; Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK., Dhillo WS; Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK.; Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK., Abbara A; Section of Endocrinology and Investigative Medicine, Imperial College London, London, UK.; Department of Endocrinology, Imperial College Healthcare NHS Trust, London, UK.
Jazyk: angličtina
Zdroj: Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2024 Oct; Vol. 1540 (1), pp. 21-46. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1111/nyas.15220
Abstrakt: Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea, resulting in anovulation and infertility, and is a low estrogen state that increases the risk of cardiovascular disease and impairs bone health. FHA is characterized by acquired suppression of physiological pulsatile gonadotropin-releasing hormone (GnRH) release by the hypothalamus in the absence of an identifiable structural cause, resulting in a functional hypogonadotropic hypogonadism. FHA results from either decreased energy intake and/or excessive exercise, leading to low energy availability and weight loss-often in combination with psychological stress on top of a background of genetic susceptibility. The hypothalamic neuropeptide kisspeptin is a key component of the GnRH pulse generator, tightly regulating pulsatile GnRH secretion and the downstream reproductive axis. Here, we review the physiological regulation of pulsatile GnRH secretion by hypothalamic kisspeptin neurons and how their activity is modulated by signals of energy status to affect reproductive function. We explore endocrine factors contributing to the suppression of GnRH pulsatility in the pathophysiology of FHA and how hypothalamic kisspeptin neurons likely represent a final common pathway through which these factors affect GnRH pulse generation. Finally, we discuss the therapeutic potential of kisspeptin as a novel treatment for women with FHA.
(© 2024 The Author(s). Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of The New York Academy of Sciences.)
Databáze: MEDLINE
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