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ME/CFS Atlas — A public knowledge atlas for ME/CFS

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ME/CFS Atlas is an evidence reference platform, not a medical provider. Content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

Evidence browser

Search and filter 6,121 studies by evidence level, diagnostic criteria, PEM status, and research domain. Each entry links to the original source.

Studies sorted by evidence level, then year. Browse by topic instead →

Evidence level (E0–E3) reflects study type and replication, not methodological quality. A weak systematic review still sits at E0. How evidence levels work →

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130 studies

E0 — Consensus629E1 — Replicated319E2 — Moderate2,757E3 — Preliminary2,416

ME/CFS4,010Long COVID208Post-infectious188Overlapping1,031

Required for diagnosis409Not specified / unclear2,191Not required3,521

Post-Exertional Malaise1,040Cognitive Dysfunction1,712Pain1,606Unrefreshing Sleep787Orthostatic Intolerance470

Cytokines812Gene Expression564Metabolomics469Neuroimaging464Autoantibodies454

Infection-Triggered1,158Long COVID Overlap563Pediatric494Severe227

Strong Phenotyping427Sex-Stratified325Severe ME Included115

Systematic Review256Meta-Analysis60RCT299

Peer-reviewed6,064Preprint3Unclear54

101–120 of 130 studies

E3 PreliminaryMechanismPEM not requiredObservational

Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or chronic fatigue syndrome.

Crofford, Leslie J, Young, Elizabeth A, Engleberg, N Cary et al.·Brain, behavior, and immunity·2004

This study measured stress hormones (ACTH and cortisol) throughout a 24-hour period in patients with fibromyalgia, chronic fatigue syndrome, or both, compared to healthy controls. Researchers found that fibromyalgia patients had abnormal cortisol patterns—particularly elevated levels in the evening and delayed decline throughout the day—suggesting their stress hormone system doesn't recover properly. Chronic fatigue syndrome patients showed some differences but they were smaller and not statistically significant.

Endocrine Disruption

E3 PreliminaryReviewPEM not requiredReview-Narrative

The HPA axis and the genesis of chronic fatigue syndrome.

Cleare, Anthony J·Trends in endocrinology and metabolism: TEM·2004

This review examines whether ME/CFS involves problems with the body's stress hormone system (the HPA axis). While people with long-standing ME/CFS show some changes in this system, early studies suggest these changes may not be present when the illness first develops. Interestingly, lifestyle factors like inactivity and poor sleep may cause these changes, and they can sometimes improve when these factors are addressed.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

Fatigue in neurological disorders.

Chaudhuri, Abhijit, Behan, Peter O·Lancet (London, England)·2004

This 2004 review article examines fatigue across multiple neurological conditions, including ME/CFS. The authors describe fatigue as occurring in two main forms: peripheral fatigue (muscle weakness) and central fatigue (difficulty sustaining mental or physical effort). The review observes that fatigue in these conditions is associated with changes in brain structure and function, though the authors note that treatment remains largely symptomatic rather than targeted at underlying causes.

Endocrine Disruption

E3 PreliminaryMechanismPEM not requiredMechanistic

Small adrenal glands in cats with feline interstitial cystitis.

Westropp, Jodi L, Welk, Kristin A, Buffington, C A Tony·The Journal of urology·2003

This study found that cats with a painful bladder condition called feline interstitial cystitis had smaller adrenal glands (organs that make stress hormones) and produced less cortisol when stimulated compared to healthy cats. The researchers suggest this might indicate a mild form of adrenal insufficiency, similar to what has been observed in some people with chronic fatigue syndrome.

Endocrine Disruption

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Assessment of cortisol response with low-dose and high-dose ACTH in patients with chronic fatigue syndrome and healthy comparison subjects.

Gaab, Jens, Hüster, D, Peisen, R et al.·Psychosomatics·2003

This study tested whether ME/CFS patients have problems with cortisol, a stress hormone made by the adrenal glands. Researchers gave 18 ME/CFS patients and 18 healthy people a hormone called ACTH (in both low and high doses) to stimulate cortisol production. The results showed no difference between the two groups, suggesting that ME/CFS is unlikely caused by faulty adrenal glands.

Endocrine Disruption

E3 PreliminaryReviewPEM not requiredReview-Narrative

Glucocorticoids and glucocorticoid receptors: mediators of fatigue?

Cleare, A J·Acta neuropsychiatrica·2003

This study looks at whether a hormone system called the HPA axis—which controls stress responses and cortisol production—might explain why people with ME/CFS experience severe fatigue. Researchers found that some patients have lower cortisol levels and changes in how their bodies respond to stress, and that giving cortisol replacement therapy in some cases improved fatigue. However, the changes weren't the same in all patients, suggesting multiple different factors may be contributing to fatigue rather than one single problem.

Endocrine Disruption

E3 PreliminaryCommentaryPEM unclearEditorial

Chronic fatigue syndrome in the psychiatric practice.

Van Duyse, A, Mariman, A, Poppe, C et al.·Acta neuropsychiatrica·2002

This review examines how psychiatric symptoms interact with ME/CFS. Many people with ME/CFS also experience depression, anxiety, or sleep problems, and doctors often miss these conditions. The study found that while antidepressant medications help with mood and social functioning, they don't improve fatigue itself. Cognitive behavioral therapy and graded exercise were the only treatments shown to actually improve fatigue and other ME/CFS symptoms.

Endocrine Disruption

E3 PreliminaryMechanismPEM not requiredObservational

Abnormalities in response to vasopressin infusion in chronic fatigue syndrome.

Altemus, M, Dale, J K, Michelson, D et al.·Psychoneuroendocrinology·2001

This study tested how the bodies of ME/CFS patients respond to a hormone called vasopressin. Researchers compared 19 patients with ME/CFS to 19 healthy volunteers by giving them vasopressin infusions and measuring hormone levels in their blood. ME/CFS patients showed a weaker response in a key stress hormone called ACTH, suggesting their brain may not be producing enough of another hormone called CRH that helps control stress responses.

Endocrine Disruption

E3 PreliminaryReviewPEM not requiredReview-Narrative

Psychoneuroendocrinological contributions to the etiology of depression, posttraumatic stress disorder, and stress-related bodily disorders: the role of the hypothalamus-pituitary-adrenal axis.

Ehlert, U, Gaab, J, Heinrichs, M·Biological psychology·2001

This study examines how stress affects hormone levels in the body, particularly through a system called the HPA axis that controls the release of cortisol and other stress hormones. The researchers found that people with depression tend to have too much HPA activity, while people with chronic fatigue syndrome and post-traumatic stress disorder tend to have too little. Understanding these differences may help doctors better diagnose and treat these conditions.

Endocrine Disruption

E3 PreliminaryTrialPEM not requiredRCT

Impact of cortisol on buspirone stimulated prolactin release: a double-blind placebo-controlled study.

Dinan, T G, Scott, L V, Thakore, J et al.·Psychoneuroendocrinology·2001

This study tested whether a drug called buspirone can trigger the release of a hormone called prolactin, and whether a person's baseline stress hormone (cortisol) level affects this response. Fifty healthy volunteers received either buspirone or placebo in a blinded trial. The researchers found that buspirone did increase prolactin levels, and importantly, people with higher baseline cortisol levels showed a stronger prolactin response.

Endocrine Disruption

E3 PreliminaryCohortPEM unclear

Recovery from chronic fatigue syndrome associated with changes in neuroendocrine function.

Sharma, A, Oyebode, F, Kendall, M J et al.·Journal of the Royal Society of Medicine·2001

This study looked at whether people who recovered from ME/CFS showed changes in their body's hormone and nervous system function compared to those still sick and healthy controls. The researchers examined whether normalizing these biological systems was connected to getting better from the illness.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

Neuroendocrine perturbations in fibromyalgia and chronic fatigue syndrome.

Neeck, G, Crofford, L J·Rheumatic diseases clinics of North America·2000

This review examines how hormone systems work differently in people with ME/CFS and fibromyalgia. In ME/CFS, the stress hormone system appears to be underactive, possibly due to problems in the brain. In fibromyalgia, the opposite seems true—the stress hormone system appears overactive, likely as the body's response to chronic pain. Understanding these differences could help explain why these conditions feel so different and might guide better treatments.

Endocrine Disruption

E3 PreliminaryCohortPEM not requiredObservational

A pilot study employing Dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome.

Himmel, P B, Seligman, T M·Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases·1999

This study tested whether giving DHEA (a hormone supplement) could help ME/CFS patients who had low DHEA levels. Researchers found that 23 women taking DHEA for 6 months experienced improvements in pain, fatigue, anxiety, memory, and thinking. However, this was a small, uncontrolled study, so larger, more rigorous trials are needed to confirm these results.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

The neuroendocrinology of chronic fatigue syndrome: focus on the hypothalamic-pituitary-adrenal axis.

Scott, L V, Dinan, T G·Functional neurology·1999

This study examined how the stress-response system in the brain works differently in people with ME/CFS. The researchers focused on the hypothalamic-pituitary-adrenal (HPA) axis, which is the body's main system for managing stress and producing cortisol. The study reviewed evidence suggesting this system may not function normally in ME/CFS patients, potentially contributing to their symptoms.

Endocrine Disruption

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Small adrenal glands in chronic fatigue syndrome: a preliminary computer tomography study.

Scott, L V, Teh, J, Reznek, R et al.·Psychoneuroendocrinology·1999

This study looked at whether the adrenal glands (small organs that help manage stress and energy) are physically smaller in people with ME/CFS. Researchers used CT scans to measure adrenal gland size in 8 ME/CFS patients who showed signs of adrenal underfunction and compared them to 55 healthy people. They found that the adrenal glands in ME/CFS patients were about 50% smaller than in healthy controls, suggesting that adrenal shrinkage may occur in some ME/CFS patients.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

The hypothalamic-pituitary-adrenal stress axis in fibromyalgia and chronic fatigue syndrome.

Crofford, L J·Zeitschrift fur Rheumatologie·1998

This review examines the stress response system (HPA axis) in fibromyalgia and chronic fatigue syndrome. The authors suggest that problems with this stress system may be connected to common symptoms like pain, exhaustion, sleep problems, and mood changes. Several treatments that help patients—including exercise and certain antidepressants—appear to work partly by affecting this stress response system.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

Neurobehavioral properties of chemical sensitivity syndromes.

Weiss, B·Neurotoxicology·1998

This review examines four conditions that involve chemical sensitivity and fatigue-like symptoms: Multiple Chemical Sensitivity Syndrome, Sick Building Syndrome, Chronic Fatigue Syndrome, and Gulf War Syndrome. The authors explore different theories about why people develop these conditions, including psychiatric factors, learned behavioral responses, changes in how the nervous system works, and problems with the immune system's stress response. The review suggests that laboratory studies and controlled clinical trials could help determine which explanations are correct.

Pain and SensitizationEndocrine Disruption

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Dehydroepiandrosterone sulfate deficiency in chronic fatigue syndrome.

Kuratsune, H, Yamaguti, K, Sawada, M et al.·International journal of molecular medicine·1998

This study found that most ME/CFS patients in Japan had lower-than-normal levels of a hormone called DHEA-S, which is made by the adrenal glands. DHEA-S helps regulate mood, memory, stress response, sleep, and anxiety. The researchers suggest that low DHEA-S levels might explain some of the brain-related symptoms ME/CFS patients experience, like depression and cognitive problems.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

Illness from low levels of environmental chemicals: relevance to chronic fatigue syndrome and fibromyalgia.

Bell, I R, Baldwin, C M, Schwartz, G E·The American journal of medicine·1998

Some people with ME/CFS and fibromyalgia react strongly to small amounts of everyday chemicals (like fragrances or pesticides) that don't normally harm others. This paper reviews evidence suggesting that the brain's limbic system—which controls emotions and basic body functions—may become overly sensitive to these chemicals, creating a chain reaction that affects multiple body systems. The authors propose that certain people are born with or develop a heightened sensitivity to this kind of stimulation, which could explain why some ME/CFS patients feel sick from exposure to low levels of chemicals.

Pain and SensitizationEndocrine Disruption

E3 PreliminaryMechanismPEM not requiredMechanistic

Evidence for and pathophysiologic implications of hypothalamic-pituitary-adrenal axis dysregulation in fibromyalgia and chronic fatigue syndrome.

Demitrack, M A, Crofford, L J·Annals of the New York Academy of Sciences·1998

This study found that people with ME/CFS have reduced activity in their stress-response system—a network in the brain called the HPA axis that normally helps the body cope with physical and emotional challenges. The researchers discovered that this underactive response pattern is different from what happens in depression, and it may explain why stress and exertion worsen ME/CFS symptoms. The findings suggest that problems with specific brain chemicals involved in stress regulation may contribute to the condition.

Endocrine Disruption

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PEM Immune Neuro Metabolic Biomarkers Severe ME Long COVID Cognitive

Curated Collections

Thematic groupings by clinical question or research area.

Neuroinflammation Evidence

PET imaging and other studies providing evidence for brain inflammation in ME/CFS.

Metabolism & Mitochondria

Metabolomics and mitochondrial function studies revealing energy metabolism disruption.

Biomarkers

Studies identifying potential biological markers for ME/CFS diagnosis and stratification.

PEM-Specific Research

Studies specifically examining post-exertional malaise, the hallmark symptom of ME/CFS.