Papadopoulos, Andrew S, Cleare, Anthony J · Nature reviews. Endocrinology · 2011 · DOI
ME/CFS patients often have abnormal levels of cortisol, a stress hormone produced by the body. This review found that people with ME/CFS tend to have lower cortisol levels than healthy people, with less variation throughout the day and a weaker response to stress. These hormone changes are linked to worse symptoms and disability, and treatments like cognitive behavioral therapy may help restore more normal cortisol levels.
HPA axis dysfunction appears to be a consistent biological feature of ME/CFS that correlates with disease severity and treatment response, potentially offering a measurable biomarker and therapeutic target. Understanding the multifactorial causes of these hormonal changes—including modifiable factors like activity level and depression—may inform personalized treatment approaches for this poorly understood condition.
This review does not prove that HPA axis dysfunction causes ME/CFS, only that it is associated with the condition; the direction of causality remains unclear. It does not establish which HPA abnormalities are primary versus secondary consequences of illness-related factors, nor does it demonstrate that correcting cortisol levels will resolve ME/CFS symptoms.
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