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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 6,121 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

61–80 of 130 studies

E2 ModerateMechanismPEM not requiredMechanistic

Desmopressin augments pituitary-adrenal responsivity to corticotropin-releasing hormone in subjects with chronic fatigue syndrome and in healthy volunteers.

Scott, L V, Medbak, S, Dinan, T G·Biological psychiatry·1999

This study tested whether a synthetic hormone called desmopressin could improve how the pituitary gland responds to stress signals in people with ME/CFS. Researchers gave ME/CFS patients and healthy volunteers different hormone combinations and measured their stress hormone responses. When desmopressin was added to another hormone (CRH), it boosted the pituitary gland's response in both groups, but especially in people with ME/CFS.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

The 1microg short Synacthen test in chronic fatigue syndrome.

Hudson, M, Cleare, A J·Clinical endocrinology·1999

This study tested whether people with ME/CFS have lower levels of cortisol (a stress hormone) or weaker adrenal gland responses compared to healthy people. Researchers gave small doses of a hormone called Synacthen to 20 ME/CFS patients and 20 healthy controls, then measured cortisol levels over an hour. They found no significant differences between the two groups, suggesting that reduced adrenal reserve may not explain ME/CFS symptoms.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Salivary cortisol profiles in chronic fatigue syndrome.

Wood, B, Wessely, S, Papadopoulos, A et al.·Neuropsychobiology·1998

This study measured cortisol (a stress hormone) levels in the saliva of 10 people with ME/CFS and 10 healthy people over a 16-hour period. Contrary to some earlier research, people with ME/CFS actually had slightly higher cortisol levels on average than healthy controls. This finding suggests that low cortisol is not the cause of fatigue in ME/CFS.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Urinary free cortisol excretion in chronic fatigue syndrome, major depression and in healthy volunteers.

Scott, L V, Dinan, T G·Journal of affective disorders·1998

This study measured a stress hormone called cortisol in urine samples from people with ME/CFS, people with depression, and healthy individuals. The researchers found that people with ME/CFS had lower cortisol levels than healthy people, while people with depression had higher levels. This suggests that ME/CFS and depression affect the body's stress response system in opposite ways.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Basal activity of the hypothalamic-pituitary-adrenal axis in patients with the chronic fatigue syndrome (neurasthenia).

Young, A H, Sharpe, M, Clements, A et al.·Biological psychiatry·1998

This study tested whether people with ME/CFS have abnormal levels of cortisol, a stress hormone, by measuring it in saliva and urine over 24 hours. The researchers found no difference in cortisol levels between people with ME/CFS and healthy controls, suggesting that the baseline cortisol system may not be impaired in this condition.

Endocrine Disruption

E2 ModerateCohortPEM unclearCross-Sectional

Secretion of growth hormone in patients with chronic fatigue syndrome.

Berwaerts, J, Moorkens, G, Abs, R·Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society·1998

This study looked at growth hormone levels in people with ME/CFS, because low growth hormone has been seen in related conditions like fibromyalgia. Researchers tested 20 ME/CFS patients and compared them to healthy controls, measuring growth hormone in different ways. They found that ME/CFS patients had lower levels of a growth hormone marker (IGF-I) and tended to produce less growth hormone at night, though other growth hormone tests were similar between groups.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCase-Control

Naloxone-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome.

Scott, L V, Burnett, F, Medbak, S et al.·Psychological medicine·1998

This study looked at whether an opioid-blocking drug called naloxone could trigger the body's stress hormone system in ME/CFS patients versus healthy people. The researchers found that when given naloxone, ME/CFS patients had a blunted response in one stress hormone (ACTH) compared to healthy controls, suggesting that excess opioids are not the primary cause of the stress hormone problems seen in ME/CFS.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Diurnal variation of adrenocortical activity in chronic fatigue syndrome.

MacHale, S M, Cavanagh, J T, Bennie, J et al.·Neuropsychobiology·1998

This study measured stress hormone (cortisol) levels in 30 ME/CFS patients and 15 healthy controls at different times of day. The researchers found that while individual cortisol measurements were similar between groups, ME/CFS patients showed a flattened pattern—their cortisol levels didn't drop as much in the evening as they should. Higher evening cortisol levels were connected to worse overall health and physical functioning in ME/CFS patients.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

The low dose ACTH test in chronic fatigue syndrome and in health.

Scott, L V, Medbak, S, Dinan, T G·Clinical endocrinology·1998

This study tested whether people with ME/CFS have a subtle problem with their stress hormone system, specifically the pituitary gland's ability to signal the adrenal glands to release cortisol. Using a sensitive test with a very small dose of ACTH (a hormone that triggers cortisol release), researchers found that people with ME/CFS showed a weaker cortisol response than healthy people, suggesting their adrenal system may not be functioning optimally.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

A comparison of salivary cortisol in chronic fatigue syndrome, community depression and healthy controls.

Strickland, P, Morriss, R, Wearden, A et al.·Journal of affective disorders·1998

This study measured cortisol (a stress hormone) in saliva from women with ME/CFS, women with depression, and healthy women to see if cortisol levels differed between groups. Researchers found that women with ME/CFS had lower cortisol levels, especially in the evening and morning, compared to both depressed and healthy women. This suggests that ME/CFS involves different biological changes than depression.

Endocrine Disruption

E2 ModerateBehavioralPEM not requiredCross-Sectional

The relationship between temporomandibular disorders and stress-associated syndromes.

Korszun, A, Papadopoulos, E, Demitrack, M et al.·Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics·1998

This study looked at how often jaw joint problems (temporomandibular disorder) occur together with ME/CFS and fibromyalgia. Researchers found that 42% of patients with these conditions also had jaw problems, and most of these patients had developed their general symptoms before their jaw pain started. Interestingly, most were treated only for the jaw problem with bite splints, even though they had multiple related conditions.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCase-Control

Contrasting neuroendocrine responses in depression and chronic fatigue syndrome.

Cleare, A J, Bearn, J, Allain, T et al.·Journal of affective disorders·1995

This study compared hormone levels and brain chemistry in people with ME/CFS, people with depression, and healthy controls. The researchers found that people with ME/CFS had lower cortisol (a stress hormone) and higher responses to a serotonin-related chemical, which is the opposite pattern seen in depression. This suggests ME/CFS and depression are biologically different conditions despite sometimes sharing similar symptoms like fatigue.

Endocrine Disruption

E2 ModerateMechanismPEM not requiredMechanistic

Neuroendocrine assessment of serotonin (5-HT) function in chronic fatigue syndrome.

Yatham, L N, Morehouse, R L, Chisholm, B T et al.·Canadian journal of psychiatry. Revue canadienne de psychiatrie·1995

Researchers tested whether serotonin, a chemical messenger in the brain, might be abnormal in ME/CFS. They gave patients and healthy controls a drug that stimulates serotonin release and measured hormonal responses. The study found no differences between the two groups, suggesting that serotonin dysfunction may not be the primary problem in ME/CFS.

Endocrine Disruption

E3 PreliminaryCohortPEM unclearCase-Control

Corticosteroids with low glucocorticoid activity as a potential therapeutic strategy for post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome in patients with bipolar affective disorder: A case report.

Nakajima, Kan, Ayani, Nobutaka, Matsuoka, Teruyuki et al.·PCN reports : psychiatry and clinical neurosciences·2025

This report describes one woman with bipolar disorder who developed ME/CFS-like symptoms after COVID-19 and was treated with different corticosteroids. When given standard corticosteroids (betamethasone and prednisolone), she experienced severe psychiatric side effects; when switched to hydrocortisone—a corticosteroid with different receptor properties—her physical symptoms reportedly improved without psychiatric destabilization. This is a single case and does not establish that this approach works for other patients with ME/CFS or bipolar disorder.

Endocrine Disruption

E3 PreliminaryMechanismPEM unclearMechanistic

Central 5-HTergic hyperactivity induces myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-like pathophysiology.

Lee, Jin-Seok, Kang, Ji-Yun, Park, Samuel-Young et al.·Journal of translational medicine·2024

Researchers used mouse models to test whether excessive serotonin (a brain chemical) might be associated with ME/CFS-like symptoms. When they increased serotonin levels in mice's brains, the animals showed fatigue and behavioural changes resembling ME/CFS features, along with changes in stress hormone responses. These are early findings in animals and do not yet tell us whether the same mechanism operates in humans with ME/CFS.

Endocrine Disruption

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

SEMIPARAMETRIC BIVARIATE HIERARCHICAL STATE SPACE MODEL WITH APPLICATION TO HORMONE CIRCADIAN RELATIONSHIP.

You, Mengying, Guo, Wensheng·The annals of applied statistics·2024

This study looked at two stress hormones—ACTH and cortisol—in people with ME/CFS and fibromyalgia compared to healthy controls. Using a new mathematical method to track these hormones over time, researchers found that healthy people show a normal daily rhythm in how these hormones work together, while patients with ME/CFS and fibromyalgia show an irregular, unpredictable pattern instead.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

The Link Between Empty Sella Syndrome, Fibromyalgia, and Chronic Fatigue Syndrome: The Role of Increased Cerebrospinal Fluid Pressure.

Hulens, Mieke, Dankaerts, Wim, Rasschaert, Ricky et al.·Journal of pain research·2023

This review explores a possible connection between three conditions—empty sella syndrome, fibromyalgia, and ME/CFS—that may all involve increased pressure from cerebrospinal fluid around the brain and pituitary gland. The authors found that these conditions share similar symptoms (fatigue, pain, headaches, vision problems) and similar hormone imbalances, suggesting that fluid pressure problems might be a common underlying cause worth investigating further.

Endocrine Disruption

E3 PreliminaryCohortPEM unclearCase-Control

Systemic exertion intolerance disease associated to neuroendocrine dysfunction and cortical atrophy: a case report.

López-Amador, Noé·Family practice·2023

This case report describes one patient with ME/CFS who had low levels of certain hormones (thyroid and adrenal hormones) and abnormally high cortisol excretion, alongside brain changes visible on CT scan. Treatment with low-dose modafinil, combined with non-drug approaches, was reported to improve symptoms in this patient. However, this is a single case and does not establish whether these findings apply to other ME/CFS patients or whether the treatment would work for them.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

COVID-19 and chronic fatigue syndrome: An endocrine perspective.

Bansal, Rashika, Gubbi, Sriram, Koch, Christian A·Journal of clinical & translational endocrinology·2022

Some people who recover from COVID-19 experience long-lasting exhaustion and other debilitating symptoms similar to ME/CFS. This review examines how COVID-19 might affect the body's hormone systems, particularly the glands that control stress response and energy levels. The authors suggest doctors should check patients' hormone levels as part of their care plan.

Endocrine DisruptionLong COVID Overlap

E3 PreliminaryMechanismPEM unclearMechanistic

Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Pereira, Gerard, Gillies, Hunter, Chanda, Sanjay et al.·Frontiers in systems neuroscience·2021

Researchers tested a new drug called CT38s that targets a receptor in the brain called CRFR2, which they believe may be overactive in ME/CFS. Fourteen ME/CFS patients received a single infusion of this drug, and most experienced symptom improvement that lasted at least 28 days. Side effects were mild and similar to typical ME/CFS symptoms, suggesting the drug was working on systems related to the disease.

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.