Kisspeptin in functional hypothalamic amenorrhea: pathophysiology and therapeutic potential
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2024-10-01
Date Acceptance
2024-09-01
Citation
Annals of the New York Academy of Sciences, 2024, 1540 (1), pp.21-46
ISSN
0077-8923
Publisher
Wiley
Start Page
21
End Page
46
Journal / Book Title
Annals of the New York Academy of Sciences
Volume
1540
Issue
1
Copyright Statement
© 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. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39287750
Subjects
amenorrhea
anovulation
ARCUATE NUCLEUS
BONE-MINERAL DENSITY
functional hypothalamic amenorrhea
GONADOTROPIN-RELEASING-HORMONE
hypogonadotropic hypogonadism
kisspeptin
LUTEINIZING-HORMONE
Multidisciplinary Sciences
NEUROKININ B
PROOPIOMELANOCORTIN MESSENGER-RNA
PROTEIN-COUPLED RECEPTOR
REPRODUCTIVE FUNCTION
Science & Technology
Science & Technology - Other Topics
SEXUAL-DIMORPHISM
STRESS-INDUCED SUPPRESSION
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2024-09-17