Blockmans, Daniel, Persoons, Philippe, Van Houdenhove, Boudewijn et al. · The American journal of medicine · 2003 · DOI
Researchers tested whether a combination of two medications (hydrocortisone and fludrocortisone) could reduce fatigue and improve well-being in ME/CFS patients. Over 6 months, 80 patients took either the medication combination or placebo in a blinded study where neither patients nor doctors knew which they were receiving. The medications did not help—patients reported the same level of fatigue and well-being whether they were taking the drugs or placebo.
This rigorous, negative trial helps clinicians and patients understand that hormonal replacement therapy targeting the hypothalamic-pituitary-adrenal axis—a plausible biological target in ME/CFS—does not provide symptom relief at the tested doses. It prevents patients from pursuing an ineffective treatment pathway and redirects research focus toward other biological mechanisms and therapeutic approaches.
This study does not prove that HPA axis dysfunction is not present in ME/CFS, only that correcting it with this specific drug combination at these doses does not alleviate symptoms. It also does not exclude the possibility that higher doses, different drug combinations, or patient subsets might respond differently. Negative findings in a controlled trial do not establish that no biological abnormality exists.
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
Blockmans, Daniel, Persoons, Philippe, Van Houdenhove, Boudewijn, Lejeune, Marina, & Bobbaers, Herman (2003). Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study.. The American journal of medicine. https://doi.org/10.1016/s0002-9343(03)00182-7
BibTeX
@article{mecfsatlas-blockmans-2003-combination-therapy,
author = {Blockmans, Daniel and Persoons, Philippe and Van Houdenhove, Boudewijn and Lejeune, Marina and Bobbaers, Herman},
title = {Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study.},
journal = {The American journal of medicine},
year = {2003},
doi = {10.1016/s0002-9343(03)00182-7},
note = {PubMed: 12829200},
url = {https://www.mecfsatlas.com/evidence/blockmans-2003-combination-therapy},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/blockmans-2003-combination-therapy
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