Cleare, A J, Heap, E, Malhi, G S et al. · Lancet (London, England) · 1999 · DOI
This study tested whether low-dose hydrocortisone (a steroid hormone) could help people with ME/CFS feel less fatigued. 32 patients took either hydrocortisone or placebo for one month each in random order. Patients on hydrocortisone reported more improvement in fatigue than those on placebo, and about one-quarter of patients on hydrocortisone had fatigue levels drop to normal range. However, the improvement was modest and the study only lasted one month.
This study was the first to formally test hydrocortisone therapy in strictly-defined ME/CFS, providing early evidence that some patients may experience fatigue reduction from this low-dose approach. The finding challenges the assumption that ME/CFS is purely psychiatric and supports investigation of endocrine dysfunction in the condition.
This study does not establish that hydrocortisone is a clinically useful long-term treatment, as only 1-month treatment periods were tested. It does not prove that hypocortisolism causes ME/CFS, only that some patients with the condition show cortisol-related improvements. The study cannot determine whether longer-term use would maintain benefit or produce adverse effects.
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, Heap, E, Malhi, G S, Wessely, S, O'Keane, V, & Miell, J (1999). Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial.. Lancet (London, England). https://doi.org/10.1016/S0140-6736(98)04074-4
BibTeX
@article{mecfsatlas-cleare-1999-low-dose,
author = {Cleare, A J and Heap, E and Malhi, G S and Wessely, S and O'Keane, V and Miell, J},
title = {Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial.},
journal = {Lancet (London, England)},
year = {1999},
doi = {10.1016/S0140-6736(98)04074-4},
note = {PubMed: 9989716},
url = {https://www.mecfsatlas.com/evidence/cleare-1999-low-dose},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-25. https://www.mecfsatlas.com/evidence/cleare-1999-low-dose
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