Cleare, Anthony J · Trends in endocrinology and metabolism: TEM · 2004 · DOI
This review examines whether ME/CFS involves problems with the body's stress hormone system (the HPA axis). While people with long-standing ME/CFS show some changes in this system, early studies suggest these changes may not be present when the illness first develops. Interestingly, lifestyle factors like inactivity and poor sleep may cause these changes, and they can sometimes improve when these factors are addressed.
Understanding whether HPA axis changes cause ME/CFS or result from it has major implications for treatment strategies. If these changes are consequences rather than causes, interventions targeting the HPA axis alone may be insufficient, but addressing behavior and lifestyle might help. This challenges assumptions about the fundamental biology of ME/CFS and redirects research focus toward prevention and early intervention.
This study does not prove that the HPA axis plays no role in ME/CFS pathogenesis—only that it may not be a primary causative factor. The review cannot establish definitive causal relationships between lifestyle factors and HPA changes, as it synthesizes existing literature rather than presenting new experimental data. It also does not address whether HPA dysfunction might be important in specific subgroups of ME/CFS patients.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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Primary citation
Cleare, Anthony J (2004). The HPA axis and the genesis of chronic fatigue syndrome.. Trends in endocrinology and metabolism: TEM. https://doi.org/10.1016/j.tem.2003.12.002
BibTeX
@article{mecfsatlas-cleare-2004-hpa-axis,
author = {Cleare, Anthony J},
title = {The HPA axis and the genesis of chronic fatigue syndrome.},
journal = {Trends in endocrinology and metabolism: TEM},
year = {2004},
doi = {10.1016/j.tem.2003.12.002},
note = {PubMed: 15036250},
url = {https://www.mecfsatlas.com/evidence/cleare-2004-hpa-axis},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/cleare-2004-hpa-axis
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