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FHA is characterized by acquired suppression of physiological pulsatile gonadotropin\u2010releasing 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\u2014often 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.<\/jats:p>","DOI":"10.1111\/nyas.15220","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T14:54:20Z","timestamp":1726584860000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Kisspeptin in functional hypothalamic amenorrhea: Pathophysiology and therapeutic potential"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0794-8975","authenticated-orcid":false,"given":"Aaran H.","family":"Patel","sequence":"first","affiliation":[{"name":"Section of Endocrinology and Investigative Medicine Imperial College London  London UK"},{"name":"Department of Endocrinology Chelsea and Westminster Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanyada","family":"Koysombat","sequence":"additional","affiliation":[{"name":"Section of 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