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Cited by 61Hypothalamic control of reproductive hormonesOvarian function and disordersPituitary Gland Disorders and Treatments

Where Have the Periods Gone? The Evaluation and Management of Functional Hypothalamic Amenorrhea

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Sophie Gibson, Marie Eve, Fleming, Nathalie, Zuijdwijk, Caroline, Dumont, Tania·2020·Journal of Clinical Research in Pediatric Endocrinology
DOI 10.4274/jcrpe.galenos.2019.2019.s0178PMC PMC7053439
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Abstract

Functional hypothalamic amenorrhea (FHA) is a common cause of amenorrhea in adolescent girls. It is often seen in the setting of stress, weight loss, or excessive exercise. FHA is a diagnosis of exclusion. Patients with primary or secondary amenorrhea should be evaluated for other causes of amenorrhea before a diagnosis of FHA can be made. The evaluation typically consists of a thorough history and physical examination as well as endocrinological and radiological investigations. FHA, if prolonged, can have significant impacts on metabolic, bone, cardiovascular, mental, and reproductive health. Management often involves a multidisciplinary approach, with a focus on lifestyle modification. Depending on the severity, pharmacologic therapy may also be considered. The aim of this paper is to present a review on the pathophysiology, clinical findings, diagnosis, and management approaches of FHA in adolescent girls.

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  • Changes in leptin, ghrelin, peptide YY, insulin, and increased cortisol negatively impact GnRH secretion, resulting in functional hypothalamic amenorrhea in females.

    “Changes in these four hormones, as well as increased cortisol levels in response to bodily stress, all negatively impact gonadotropin-releasing hormone (GnRH) secretion, resulting in functional hypothalamic amenorrhea in females [4,12].”

    From Low Energy Availability and Relative Energy Deficiency in Sport: A Systematic Review and Meta-analysis (2025) · cites this paper as [12]

    The Pathophysiology section reports altered leptin, ghrelin, peptide YY, and insulin levels in patients with FHA, increased cortisol, and suppressed GnRH secretion. It hypothesizes that stress-related CRH suppresses GnRH pulsatility, but does not say that cortisol or each of the four metabolic hormones directly suppresses GnRH and thereby causes FHA. Page numbers are not available in our copy. (LLM, conf=0.88)

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1 of the 116 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. [27]No Authors List Committee Opinion No.702: Female Athlete Triad. Obstet Gynecol 2017 129 160 167 28538496
  2. [49]Miller KK Klibanski A Clinical review 106: Amenorrheic bone loss J Clin Endocrinol Metab 1999 84 1775 1783 10372663

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Related

Authors
Sophie Gibson, M. E., Fleming, N., Zuijdwijk, C., & Dumont, T.
Affiliations
University of Ottawa (CA)
Corresponding author
Dumont, Tania
ORCID
Venue
Journal of Clinical Research in Pediatric Endocrinology
Publisher
Galenos Yayinevi
Published
2020-01-01
Volume
12
Issue
1
Pages
18-27
ISSN
  • 1308-5727 (ISSN-L)
  • 1308-5735
DOI
10.4274/jcrpe.galenos.2019.2019.s0178
PMC
PMC7053439
OpenAlex
W3004876663
Cited by
61
References
116
Citations by year
2026: 7 · 2025: 11 · 2024: 19 · 2023: 9 · 2022: 9 · 2021: 4 · 2020: 2
FWCI
0.89
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Journal of Clinical Research in Pediatric Endocrinology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
functional hypothalamic amenorrhea, amenorrhea, adolescent girls, diagnosis of exclusion, pathophysiology, lifestyle modification, pharmacotherapy, bone health, reproductive health, stress, weight loss, excessive exercise
MeSH terms
Adolescent, Amenorrhea, Female, Fertility, Humans, Hypothalamic Diseases, Life Style, Physical Examination, Psychotherapy

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