McKenzie, R, O'Fallon, A, Dale, J et al. · JAMA · 1998 · DOI
Researchers tested whether low-dose hydrocortisone (a steroid hormone) could help ME/CFS patients by addressing a potential hormone imbalance in the body. Over 12 weeks, patients taking hydrocortisone showed somewhat more improvement in overall wellness compared to those taking placebo, but the difference was small and not quite statistically significant. However, the treatment caused the body's ability to produce its own cortisol to be suppressed in 12 patients, which made doctors decide the risks were too high to recommend this treatment.
This study directly investigated the hypothalamic-pituitary-adrenal (HPA) axis dysfunction hypothesis in ME/CFS, which remains a leading biological theory. The finding that even low-dose glucocorticoid replacement can suppress patients' endogenous cortisol production highlights the complexity of HPA axis dysregulation in this disease and suggests that simple hormone replacement is not a viable treatment approach.
This study does not prove that HPA axis dysregulation plays no role in ME/CFS—only that supplementing cortisol is not an effective or safe treatment strategy. It does not establish whether higher or lower doses might be safer, nor does it rule out other HPA axis-targeted interventions. The study also cannot determine whether different patient subgroups might respond better to this therapy.
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 →
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