Zhang, Yi-Dan, Wang, Li-Na · Frontiers in endocrinology · 2024 · DOI
This review examines how ME/CFS affects the body's stress-response system, called the HPA axis, which controls cortisol (a stress hormone). Research shows that people with ME/CFS tend to have lower cortisol levels, less natural variation in cortisol throughout the day, and a weaker response to stress compared to healthy people. Understanding these hormone changes may help explain why ME/CFS patients experience extreme fatigue and other symptoms, and could guide new treatments.
Understanding HPA axis dysfunction is critical because the stress-response system regulates energy, immune function, and sleep—all severely disrupted in ME/CFS. This review consolidates evidence linking hormonal abnormalities to symptoms, which could inform development of targeted treatments and explain why some patients don't respond to standard fatigue therapies. It provides a biological framework that validates ME/CFS as a physiological disorder rather than purely psychiatric.
This review does not establish that HPA axis dysfunction is the sole cause of ME/CFS or that it is present in all patients—the authors note significant controversy and variability across studies. It does not prove that correcting cortisol levels will cure ME/CFS, only that associations exist. The review cannot determine whether HPA changes are primary drivers of illness or secondary consequences of systemic dysfunction.
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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