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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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© 2026 ME/CFS Atlas

ME/CFS Evidence Browser — Classified Studies on Myalgic Encephalomyelitis

Evidence browser

Search and filter 6,189 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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132 studies

E0 — Consensus649E1 — Replicated321E2 — Moderate2,796E3 — Preliminary2,423

ME/CFS4,033Long COVID222Post-infectious189Overlapping1,058

Required for diagnosis417Not specified / unclear2,235Not required3,537

Post-Exertional Malaise1,075Cognitive Dysfunction1,744Pain1,625Unrefreshing Sleep802Orthostatic Intolerance483

Cytokines820Gene Expression570Metabolomics476Neuroimaging471Autoantibodies458

Infection-Triggered1,178Long COVID Overlap597Pediatric494Severe232

Strong Phenotyping444Sex-Stratified328Severe ME Included119

Systematic Review269Meta-Analysis61RCT301

Peer-reviewed6,132Preprint3Unclear54

41–60 of 132 studies

E2 ModerateCohortPEM not requiredLongitudinal

Cortisol and severe fatigue: a longitudinal study in adolescent girls.

Ter Wolbeek, Maike, van Doornen, Lorenz J P, Coffeng, Luc E et al.·Psychoneuroendocrinology·2007

This study looked at whether girls with severe, ongoing fatigue have different stress hormone (cortisol) levels than girls without fatigue. Researchers tested cortisol levels at different times over a year and found that while fatigued girls reported much worse symptoms overall, their cortisol levels were actually normal and similar to non-fatigued girls. This suggests that severe fatigue in adolescents may not be caused by problems with how the body manages stress hormones.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCase-Control

Chronic fatigue syndrome and high allostatic load.

Maloney, Elizabeth M, Gurbaxani, Brian M, Jones, James F et al.·Pharmacogenomics·2006

This study looked at whether people with ME/CFS have higher "allostatic load"—a measure of how much physical stress the body is under based on things like blood pressure, cortisol levels, and waist-to-hip ratio. Researchers compared 43 ME/CFS patients to 60 healthy people and found that ME/CFS patients were about twice as likely to have high allostatic load. This suggests that ME/CFS may involve ongoing physical stress on the body's systems.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Clinical burnout is not reflected in the cortisol awakening response, the day-curve or the response to a low-dose dexamethasone suppression test.

Mommersteeg, Paula M C, Heijnen, Cobi J, Verbraak, Marc J P M et al.·Psychoneuroendocrinology·2006

This study tested whether burnout affects the body's stress hormone system (cortisol levels) in the same way that chronic stress does. Researchers measured cortisol levels in 74 people with burnout and 35 healthy people using saliva samples and a hormone suppression test. They found no differences between the two groups, suggesting that burnout may not change cortisol patterns the way researchers expected.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCase-Control

Urinary cortisol and cortisol metabolite excretion in chronic fatigue syndrome.

Jerjes, Walid K, Taylor, Norman F, Peters, Timothy J et al.·Psychosomatic medicine·2006

This study measured stress hormone levels in urine from people with ME/CFS and healthy controls to see if ME/CFS patients produce less cortisol (a hormone made during stress). The researchers found no major difference in total cortisol output between the two groups when measuring both cortisol and its breakdown products, though free cortisol levels were slightly lower in patients and related to fatigue severity.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome.

Jerjes, Walid K, Peters, Timothy J, Taylor, Norman F et al.·Journal of psychosomatic research·2006

This study measured stress hormone levels in urine samples from ME/CFS patients and healthy people throughout the day. Researchers found that ME/CFS patients had lower levels of certain stress hormones (cortisol and cortisone) compared to healthy controls, though the daily pattern of these hormones was normal. Interestingly, when they looked at other related hormone measurements, they didn't see the same difference, which suggests the stress response system may not be working as hard in ME/CFS.

Endocrine Disruption

E2 ModerateCohortPEM unclearCross-Sectional

Diurnal patterns of salivary cortisol and cortisone output in chronic fatigue syndrome.

Jerjes, W K, Cleare, A J, Wessely, S et al.·Journal of affective disorders·2005

This study measured stress hormone levels (cortisol and cortisone) in saliva samples from ME/CFS patients and healthy people throughout the day. Researchers found that ME/CFS patients had lower levels of both hormones compared to healthy controls, but the daily pattern of these hormones remained similar between the two groups. This suggests that the body's stress response system may not be working at full capacity in some ME/CFS patients.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCase-Control

Normal opioid tone and hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome despite marked functional impairment.

Inder, Warrick J, Prickett, Timothy C R, Mulder, Roger T·Clinical endocrinology·2005

This study tested whether ME/CFS is caused by low levels of pain-relieving chemicals (opioids) in the brain or problems with the stress hormone system. Researchers measured hormone levels and responses in 12 ME/CFS patients and 11 healthy people, and found no differences between the groups, suggesting these hormonal systems are working normally in ME/CFS despite severe fatigue and physical limitations.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCase-Control

Disturbed adrenal function in adolescents with chronic fatigue syndrome.

Segal, T Y, Hindmarsh, P C, Viner, R M·Journal of pediatric endocrinology & metabolism : JPEM·2005

This study tested how well the adrenal glands (small glands that produce stress hormones) respond to stimulation in adolescents with ME/CFS compared to healthy teens. Researchers found that adolescents with ME/CFS had weaker adrenal responses, producing less of the hormone cortisol and taking longer to reach peak levels. These differences were more noticeable in girls than boys.

Endocrine Disruption

E2 ModerateCohortPEM not requiredObservational

24-hour pituitary and adrenal hormone profiles in chronic fatigue syndrome.

Di Giorgio, Annabella, Hudson, Marina, Jerjes, Walid et al.·Psychosomatic medicine·2005

Researchers measured hormone levels in ME/CFS patients and healthy people over a full 24-hour period to see if the body's stress-hormone system works differently. They found that ME/CFS patients had lower levels of ACTH (a hormone that signals the adrenal glands) throughout the day, especially in the morning when levels normally peak. Other hormones tested were normal, suggesting a subtle problem with how the stress-hormone system is regulated.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Fatigue and regulation of the hypothalamo-pituitary-adrenal axis in multiple sclerosis.

Gottschalk, Michaela, Kümpfel, Tania, Flachenecker, Peter et al.·Archives of neurology·2005

This study looked at fatigue in multiple sclerosis (MS) patients and examined whether their stress hormone system (HPA axis) might be involved. Researchers tested 31 MS patients using three different fatigue questionnaires and a special hormone test. They found that MS patients with severe fatigue had higher levels of a stress hormone called ACTH compared to MS patients without fatigue.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCase-Control

Association between chronic fatigue syndrome and the corticosteroid-binding globulin gene ALA SER224 polymorphism.

Torpy, David J, Bachmann, A W, Gartside, M et al.·Endocrine research·2004

This study investigated whether a specific genetic variation in a gene called CBG (corticosteroid-binding globulin) might increase the risk of developing ME/CFS. The researchers compared 248 ME/CFS patients with 248 healthy controls and found a trend suggesting that people with two copies of a particular genetic variant (called serine224) were more common among ME/CFS patients. This variant was associated with higher CBG levels in the blood but lower cortisol levels, which could affect how the body manages stress and inflammation.

Endocrine Disruption

E2 ModerateCohortPEM unclearCase-Control

Hypothalamic-pituitary-gonadal axis hormones and cortisol in both menstrual phases of women with chronic fatigue syndrome and effect of depressive mood on these hormones.

Cevik, Remzi, Gur, Ali, Acar, Suat et al.·BMC musculoskeletal disorders·2004

This study examined hormone levels in women with ME/CFS, focusing on hormones that control the menstrual cycle and stress response. Researchers found that women with ME/CFS had lower stress hormone (cortisol) levels than healthy women, while menstrual cycle hormones were normal. Depression symptoms did not change these hormone patterns.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Salivary cortisol response to awakening in chronic fatigue syndrome.

Roberts, Amanda D L, Wessely, Simon, Chalder, Trudie et al.·The British journal of psychiatry : the journal of mental science·2004

This study tested how well the body's stress response system (controlled by the brain and hormones) works in ME/CFS patients. Researchers measured cortisol, a stress hormone, in saliva when people first woke up and for an hour afterward. They found that people with ME/CFS had a weaker cortisol response compared to healthy people, suggesting their stress-response system may not be working properly.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones.

Gur, Ali, Cevik, Remzi, Nas, Kemal et al.·Arthritis research & therapy·2004

This study examined hormone levels in women with fibromyalgia and ME/CFS, comparing them to healthy women. Researchers found that women with both conditions had lower cortisol (a stress hormone) than healthy controls, but other reproductive hormones were similar across groups. Depression symptoms appeared to be connected to even lower cortisol levels, though it's unclear whether depression causes low cortisol or low cortisol contributes to depression.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Associations between neuroendocrine responses to the Insulin Tolerance Test and patient characteristics in chronic fatigue syndrome.

Gaab, Jens, Engert, Veronika, Heitz, Vera et al.·Journal of psychosomatic research·2004

This study tested whether ME/CFS patients have problems with their stress hormone system (the HPA axis). Researchers gave 18 ME/CFS patients and 17 healthy controls a special test that triggers the body's stress response and measured their hormones. They found that ME/CFS patients had a weaker hormone response, and this weakness was linked to how long someone had been sick and how severe their fatigue was.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCase-Control

Association between serotonin transporter gene polymorphism and chronic fatigue syndrome.

Narita, Masaaki, Nishigami, Naoko, Narita, Naoko et al.·Biochemical and biophysical research communications·2003

This study looked at a specific gene that controls serotonin, a chemical messenger in the brain. Researchers compared the genetic versions of this gene in 78 ME/CFS patients and healthy controls. They found that ME/CFS patients were more likely to have a genetic variant that may reduce how much serotonin stays active in the brain, which could make people more vulnerable to developing ME/CFS.

Endocrine Disruption

E2 ModerateCohortPEM unclearObservational

Is hypercortisolaemia a factor in chronic fatigue syndrome?

Renan, M J·Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme·2003

This study investigated whether people with ME/CFS have abnormal levels of cortisol, a stress hormone produced by the body. Cortisol helps regulate energy, immune function, and stress response. The researchers wanted to understand if problems with cortisol production might explain some of the fatigue and other symptoms experienced by ME/CFS patients.

Endocrine Disruption

E2 ModerateCohortPEM not requiredObservational

[Disorder of adrenal gland function in chronic fatigue syndrome].

Zarković, Milos, Pavlović, Milorad, Pokrajac-Simeunović, Ana et al.·Srpski arhiv za celokupno lekarstvo·2003

This study tested how well the adrenal glands (which produce stress hormones) respond to a small dose of ACTH hormone in people with ME/CFS, compared to healthy people and those with adrenal problems from steroid use. The researchers found that some people with ME/CFS had a slower initial hormone response similar to adrenal insufficiency, but the response eventually caught up. This suggests ME/CFS patients may have a subtle problem with how quickly their adrenal glands respond to signals.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCase-Control

Low-dose dexamethasone suppression test in chronic fatigue syndrome and health.

Gaab, Jens, Hüster, Dominik, Peisen, Renate et al.·Psychosomatic medicine·2002

This study looked at how the body's stress-response system (called the HPA axis) works differently in ME/CFS patients compared to healthy people. Researchers measured cortisol levels in saliva at different times of day, and then gave participants a small dose of a steroid medication to see how well the body could shut down cortisol production. They found that ME/CFS patients' cortisol levels dropped much more dramatically and stayed suppressed longer after the medication, suggesting their stress system may be working overtime to control itself.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Urinary free cortisol in chronic fatigue syndrome.

Cleare, A J, Blair, D, Chambers, S et al.·The American journal of psychiatry·2001

This study measured a stress hormone called cortisol in the urine of people with ME/CFS and compared it to healthy controls. The researchers found that people with ME/CFS had lower cortisol levels than expected. This difference was consistent across the patient group and wasn't explained by depression, medications, sleep problems, or disability levels.

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.