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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 6,209 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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133 studies

E0 — Consensus657E1 — Replicated321E2 — Moderate2,808E3 — Preliminary2,423

ME/CFS4,042Long COVID224Post-infectious190Overlapping1,065

Required for diagnosis417Not specified / unclear2,254Not required3,538

Post-Exertional Malaise1,083Cognitive Dysfunction1,751Pain1,631Unrefreshing Sleep806Orthostatic Intolerance484

Cytokines823Gene Expression573Metabolomics478Neuroimaging472Autoantibodies461

Infection-Triggered1,183Long COVID Overlap605Pediatric496Severe232

Strong Phenotyping445Sex-Stratified330Severe ME Included119

Systematic Review273Meta-Analysis61RCT301

Peer-reviewed6,152Preprint3Unclear54

61–80 of 133 studies

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

E2 ModerateCohortPEM not requiredObservational

Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome.

Moorkens, G, Berwaerts, J, Wynants, H et al.·Clinical endocrinology·2000

This study examined hormone levels in 73 people with ME/CFS compared to 21 healthy people. Researchers found that people with ME/CFS had lower growth hormone (GH) levels, especially at night and when their body was stressed by low blood sugar. They also had higher levels of prolactin and thyroid-stimulating hormone (TSH), suggesting their brain chemistry may be imbalanced. These hormone changes were associated with increased belly fat in ME/CFS patients.

Endocrine Disruption

E2 ModerateCohortPEM not requiredCross-Sectional

Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health.

Scott, L V, Salahuddin, F, Cooney, J et al.·Journal of affective disorders·1999

This study measured several hormones related to stress in people with ME/CFS, depression, and healthy individuals. Researchers found that people with ME/CFS had significantly lower levels of DHEA and DHEA-S (hormones produced by the adrenal glands) compared to healthy people, while cortisol levels were similar across all groups. This suggests ME/CFS may involve a different hormone pattern than depression, and DHEA could potentially help diagnose or treat 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 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 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 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 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 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

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 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

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 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 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

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

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 case report describes one patient with bipolar disorder who developed ME/CFS after COVID-19 and was treated with different types of steroid medications. Strong steroids (betamethasone and prednisolone) triggered a severe manic episode requiring hospitalization, but a weaker steroid (hydrocortisone) improved her fatigue without worsening her mood. The findings suggest that choosing the right type of steroid may be important for ME/CFS patients who also have mood disorders.

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 found that excess serotonin (a brain chemical) in a specific brain region called the dorsal raphe nuclei can cause fatigue and symptoms similar to ME/CFS in mice. They tested this by giving mice high doses of common antidepressants (SSRIs) that increase serotonin levels, and the mice developed severe tiredness, difficulty with physical activity, and problems with their stress response system. This suggests that too much serotonin activity in the brain might be involved in causing ME/CFS symptoms.

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

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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.