Cleare, A J · Acta neuropsychiatrica · 2003 · DOI
This study looks at whether a hormone system called the HPA axis—which controls stress responses and cortisol production—might explain why people with ME/CFS experience severe fatigue. Researchers found that some patients have lower cortisol levels and changes in how their bodies respond to stress, and that giving cortisol replacement therapy in some cases improved fatigue. However, the changes weren't the same in all patients, suggesting multiple different factors may be contributing to fatigue rather than one single problem.
Understanding whether hormonal imbalances drive ME/CFS fatigue is crucial for developing targeted treatments. This study's finding that cortisol replacement helped some patients suggests HPA axis dysfunction could be a therapeutic target, while the heterogeneity of findings indicates that ME/CFS likely involves multiple biological pathways that future research should address.
This review does not establish that HPA axis dysfunction is the primary cause of ME/CFS—it may be a secondary consequence of other disease processes. The improvements seen with cortisol replacement do not prove causation, as the mechanism by which cortisol helps fatigue remains unclear. The absence of uniform HPA axis changes across all patients suggests that this dysfunction, if present, is not necessary or sufficient to explain all cases of ME/CFS.
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 →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Cleare, A J (2003). Glucocorticoids and glucocorticoid receptors: mediators of fatigue?. Acta neuropsychiatrica. https://doi.org/10.1046/j.1601-5215.2003.00050.x
BibTeX
@article{mecfsatlas-cleare-2003-glucocorticoids-glucocorticoid,
author = {Cleare, A J},
title = {Glucocorticoids and glucocorticoid receptors: mediators of fatigue?},
journal = {Acta neuropsychiatrica},
year = {2003},
doi = {10.1046/j.1601-5215.2003.00050.x},
note = {PubMed: 26983770},
url = {https://www.mecfsatlas.com/evidence/cleare-2003-glucocorticoids-glucocorticoid},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/cleare-2003-glucocorticoids-glucocorticoid
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