Tak, Lineke M, Cleare, Anthony J, Ormel, Johan et al. · Biological psychology · 2011 · DOI
This research reviewed 85 studies examining whether people with ME/CFS, fibromyalgia, and irritable bowel syndrome have lower levels of the stress hormone cortisol. The researchers found that ME/CFS patients do have lower cortisol levels compared to healthy people, though the difference was modest. Being female also predicted lower cortisol, particularly in fibromyalgia patients.
This meta-analysis provides the most comprehensive evidence synthesis to date regarding HPA axis dysfunction in ME/CFS, supporting the biological basis of the illness. The finding that ME/CFS shows distinct HPA abnormalities compared to other functional somatic disorders strengthens the case for ME/CFS as a distinct biological condition and may guide future diagnostic and therapeutic research.
This study does not establish that low cortisol causes ME/CFS—only that the association exists in some patients. The meta-analysis cannot explain the mechanisms underlying this hypocortisolism or determine whether it predicts disease severity, prognosis, or treatment response. Individual study quality and heterogeneity in measurement methods may affect the reliability of pooled estimates.
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
Tak, Lineke M, Cleare, Anthony J, Ormel, Johan, Manoharan, Andiappan, Kok, Iris C, Wessely, Simon, et al. (2011). Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders.. Biological psychology. https://doi.org/10.1016/j.biopsycho.2011.02.002
BibTeX
@article{mecfsatlas-tak-2011-meta-analysis,
author = {Tak, Lineke M and Cleare, Anthony J and Ormel, Johan and Manoharan, Andiappan and Kok, Iris C and Wessely, Simon and Rosmalen, Judith G M},
title = {Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders.},
journal = {Biological psychology},
year = {2011},
doi = {10.1016/j.biopsycho.2011.02.002},
note = {PubMed: 21315796},
url = {https://www.mecfsatlas.com/evidence/tak-2011-meta-analysis},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/tak-2011-meta-analysis
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