Rubin, G James, Hotopf, Matthew, Papadopoulos, Andrew et al. · Psychosomatic medicine · 2005 · DOI
This study tested whether low cortisol (a stress hormone) causes or predicts chronic fatigue by following 161 patients before and after surgery. The researchers measured cortisol levels and fatigue at multiple time points, but found that low cortisol before or after surgery did not predict who would develop fatigue. This suggests that if low cortisol is connected to chronic fatigue, it develops after symptoms begin rather than causing them.
For ME/CFS patients, understanding whether low cortisol causes fatigue or results from it has important implications for treatment development. This study uses surgery as a natural experiment to investigate fatigue etiology, providing evidence that cortisol abnormalities are not the root cause of chronic fatigue, which may redirect research and clinical attention to other mechanisms.
This study does not prove that cortisol plays no role in ME/CFS—only that low baseline cortisol is not a primary cause. The study cannot establish causality in either direction and is limited to postoperative fatigue in a surgical population, which may differ mechanistically from spontaneous-onset ME/CFS. The findings do not exclude cortisol dysregulation as a secondary feature or contributor.
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
Rubin, G James, Hotopf, Matthew, Papadopoulos, Andrew, & Cleare, Anthony (2005). Salivary cortisol as a predictor of postoperative fatigue.. Psychosomatic medicine. https://doi.org/10.1097/01.psy.0000161207.73744.4e
BibTeX
@article{mecfsatlas-rubin-2005-salivary-cortisol,
author = {Rubin, G James and Hotopf, Matthew and Papadopoulos, Andrew and Cleare, Anthony},
title = {Salivary cortisol as a predictor of postoperative fatigue.},
journal = {Psychosomatic medicine},
year = {2005},
doi = {10.1097/01.psy.0000161207.73744.4e},
note = {PubMed: 15911908},
url = {https://www.mecfsatlas.com/evidence/rubin-2005-salivary-cortisol},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/rubin-2005-salivary-cortisol
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