E0 ConsensusModerate confidencePEM not requiredReview-NarrativePeer-reviewedReviewed
A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome.
Tomas, Cara, Newton, Julia, Watson, Stuart · ISRN neuroscience · 2013 · DOI
Quick Summary
This review examined how ME/CFS affects the HPA axis, a system in the brain that controls stress hormones like cortisol. Researchers found that many ME/CFS patients have problems with this system, including lower cortisol levels and changes in how their bodies respond to stress. The review suggests that genetics, past trauma, and oxidative stress may play a role, and notes that women are more commonly affected than men.
Why It Matters
Understanding HPA axis dysfunction is crucial because it may explain some ME/CFS symptoms like fatigue and impaired stress response, and could point toward new treatments targeting hormonal regulation. If HPA axis problems are confirmed as causal, this could lead to more personalized therapeutic approaches beyond current standard treatments.
Observed Findings
- Enhanced sensitivity to corticosteroid-induced negative feedback in CFS patients
- Reduced basal cortisol levels compared to healthy controls
- Attenuated diurnal (daily) variation in cortisol secretion
- Reduced responsivity to physiological and psychological challenges
- Higher frequency of HPA axis dysregulation in female patients compared to males
Inferred Conclusions
- HPA axis dysfunction is prevalent in ME/CFS and may involve multiple pathogenic mechanisms including genetic factors, childhood trauma, and oxidative stress
- Gender differences suggest biological sex influences the development or expression of HPA axis dysregulation in ME/CFS
- Novel treatment strategies targeting HPA axis function may be beneficial given variable response to current therapies
- The temporal association between HPA dysfunction and ME/CFS warrants investigation into causal mechanisms
Remaining Questions
- Does HPA axis dysfunction cause ME/CFS, result from it, or occur independently?
- What specific genetic, traumatic, and oxidative stress factors predispose individuals to HPA dysregulation in ME/CFS?
What This Study Does Not Prove
This review does not prove that HPA axis dysfunction causes ME/CFS—it only shows the two are associated. The study cannot establish whether the hormonal problems are a primary cause, a consequence of illness, or an unrelated finding. It also does not demonstrate that treating HPA axis dysfunction would improve ME/CFS symptoms.
Tags
Symptom:Fatigue
Biomarker:Blood Biomarker
Method Flag:Mixed CohortWeak Case Definition
Metadata
- DOI
- 10.1155/2013/784520
- PMID
- 24959566
- Review status
- Editor reviewed
- Evidence level
- Higher-level evidence type — systematic reviews, meta-analyses, guidelines, or major syntheses (study type, not a quality guarantee)
- Last updated
- 12 April 2026
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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