A review of the pathophysiology of functional hypothalamic amenorrhoea in women subject to psychological stress, disordered eating, excessive exercise or a combination of these factors.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic and endocrine pathways without systematic methodology or primary human data.
PubMed 33345352 · doi:10.1111/cen.14399
What was done
This narrative review summarizes the pathophysiological mechanisms of functional hypothalamic amenorrhoea (FHA) induced by psychological stress, disordered eating, low body weight, excessive exercise, or combinations of these factors.
What was found
The abstract provides a qualitative overview of endocrine changes without reporting specific numerical data or effect estimates. FHA is characterized by suppressed gonadotrophin-releasing hormone (GnRH) pulsatility resulting in reduced luteinizing hormone (LH), low oestradiol, anovulation, and amenorrhoea. Associated metabolic and neuroendocrine profiles in low energy availability states include elevated adiponectin, ghrelin, peptide YY (PYY), basal cortisol, and growth hormone (GH), alongside decreased leptin, insulin, total T3, and insulin-like growth factor 1 (IGF-1), as well as a reduced response to corticotrophin-releasing hormone (CRH). Kisspeptin and KNDy (kisspeptin/neurokinin B/dynorphin) neuronal signaling pathways are noted as central mediators of GnRH suppression.
Why it matters
Understanding the multi-hormonal and neuroendocrine disruptions underlying FHA helps explain associated complications (such as impaired bone density, altered cardiovascular risk profile, and infertility) and highlights mechanistic pathways—such as kisspeptin signaling—that may guide future therapeutic strategies.
Limits
The abstract presents no quantitative data, effect sizes, or confidence intervals. As a narrative review, it lacks a systematic search protocol, risk-of-bias assessment, or study-selection criteria, and does not report sample sizes or primary patient outcomes.
Cited by
- supports In women, high-volume exercise combined with severe caloric deficit disrupts follicle-stimulating hormone and luteinizing hormone, leading to amenorrhea and cessation of ovulation.