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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

81–100 of 130 studies

E3 PreliminaryMechanismPEM unclearMechanistic

Characterization of Cortisol Dysregulation in Fibromyalgia and Chronic Fatigue Syndromes: A State-Space Approach.

Pednekar, Divesh Deepak, Amin, Md Rafiul, Azgomi, Hamid Fekri et al.·IEEE transactions on bio-medical engineering·2020

This study looked at how the stress hormone cortisol behaves differently in people with fibromyalgia and ME/CFS compared to healthy people. Researchers found that people with fibromyalgia clear cortisol from their bodies more slowly, causing it to build up, which then triggers the body to reduce cortisol release. People with ME/CFS show different patterns, particularly releasing less cortisol in the early morning hours.

Endocrine Disruption

E3 PreliminaryMechanismPEM unclearMechanistic

High-fidelity discrete modeling of the HPA axis: a study of regulatory plasticity in biology.

Sedghamiz, Hooman, Morris, Matthew, Craddock, Travis J A et al.·BMC systems biology·2018

This study created a simple computer model to understand how the body's stress-response system (the HPA axis) works and how it can get stuck in unhealthy patterns in conditions like ME/CFS. The researchers found that stress may push this system into a low-cortisol state and keep it there, and that certain treatments might help restore normal daily rhythms. The model worked better and required less data than previous complex models.

Endocrine Disruption

E3 PreliminaryDiagnosticPEM not requiredMethods-Paper

Modeling diurnal hormone profiles by hierarchical state space models.

Liu, Ziyue, Guo, Wensheng·Statistics in medicine·2015

This study developed a new statistical method to measure hormonal patterns in ME/CFS and fibromyalgia patients compared to healthy people. Researchers focused on ACTH, a stress hormone that naturally rises and falls throughout the day in waves. They found that the daily rhythm of this hormone was similar between patients and healthy controls, but patients' hormone pulses were weaker and less frequent.

Endocrine Disruption

E3 PreliminaryDiagnosticPEM unclearMethods-Paper

Modeling Bivariate Longitudinal Hormone Profiles by Hierarchical State Space Models.

Liu, Ziyue, Cappola, Anne R, Crofford, Leslie J et al.·Journal of the American Statistical Association·2014

This study developed a new statistical method to track how stress hormones change over time in people with ME/CFS and fibromyalgia. The researchers found that in patients with these conditions, the two main stress hormones (ACTH and cortisol) don't work together as well as they do in healthy people, suggesting their stress-response system may function differently.

Endocrine Disruption

E3 PreliminaryMechanismPEM not requiredMechanistic

Continuous stress promotes expression of VGF in melanotroph via suppression of dopamine.

Tokizane, Kyohei, Konishi, Hiroyuki, Yasui, Masaya et al.·Molecular and cellular endocrinology·2013

When the body experiences prolonged stress, it can affect how the pituitary gland (a small gland in the brain that controls many hormones) works. In this rat study, researchers found that stress caused increased production of a protein called VGF in certain pituitary cells. Interestingly, this increase happened because stress reduced levels of dopamine, a chemical messenger that normally keeps VGF levels low.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

A role for corticosteroid-binding globulin variants in stress-related disorders.

Marathe, Chinmay S, Torpy, David J·Expert review of endocrinology & metabolism·2012

This review examines how genetic variations in a protein called corticosteroid-binding globulin (CBG) may influence whether someone develops ME/CFS, fibromyalgia, or chronic pain. CBG helps transport cortisol (the body's stress hormone) in the blood, and when this protein doesn't work properly, it may affect how the body responds to stress. The researchers looked at evidence from genetic studies and animal models suggesting that inherited differences in the CBG gene could increase someone's risk of developing these stress-related conditions.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome.

Light, Kathleen C, White, Andrea T, Tadler, Scott et al.·Pain research and treatment·2012

This study looked at genes and how they are expressed (turned on or off) in people with fibromyalgia and chronic fatigue syndrome. Researchers focused on three main biological systems: the stress response system, the hormone system that controls stress, and the serotonin system (which affects mood and pain). They found that certain genes, particularly those controlling stress hormones and pain sensing, may play a role in why some people develop or maintain these conditions.

Endocrine Disruption

E3 PreliminaryMechanismPEM not requiredMechanistic

Increased HDAC in association with decreased plasma cortisol in older adults with chronic fatigue syndrome.

Jason, Leonard, Sorenson, Matthew, Sebally, Kebba et al.·Brain, behavior, and immunity·2011

This study examined stress hormone systems in older adults with ME/CFS. Researchers found that people with ME/CFS had lower levels of cortisol (a stress hormone) but higher levels of an enzyme called HDAC and lower antioxidant protection. These findings suggest that the body's stress response system isn't working properly in ME/CFS, possibly due to increased cellular stress.

Endocrine Disruption

E3 PreliminaryReviewPEM not requiredReview-Narrative

[The HPA axis in the pathogenesis of chronic fatigue syndrome].

Ursini, F, Succurro, E, Grembiale, A et al.·La Clinica terapeutica·2010

This review examines whether problems with the HPA axis—a system in your brain and body that manages stress and energy—might explain ME/CFS symptoms. The HPA axis controls cortisol and other hormones that help your body respond to stress and maintain energy levels. This article summarizes what scientists have found so far about whether HPA axis dysfunction could be a key cause of ME/CFS.

Endocrine Disruption

E3 PreliminaryMechanismPEM not requiredMechanistic

Model-based therapeutic correction of hypothalamic-pituitary-adrenal axis dysfunction.

Ben-Zvi, Amos, Vernon, Suzanne D, Broderick, Gordon·PLoS computational biology·2009

People with ME/CFS often have abnormally low cortisol levels, a hormone that helps the body manage stress and energy. This study used mathematical computer modeling to design a new treatment approach: rather than giving more cortisol (the intuitive approach), the model suggests temporarily suppressing cortisol further until the body's signaling hormone (ACTH) rises enough to trigger the system to reset itself back to normal levels. This counterintuitive strategy could work by exploiting how the body's hormone system naturally behaves.

Endocrine Disruption

E3 PreliminaryMechanismPEM unclearObservational

The effects of galantamine hydrobromide treatment on dehydroepiandrosterone sulfate and cortisol levels in patients with chronic fatigue syndrome.

Turan, Tayfun, Izgi, Hasan Basri, Ozsoy, Saliha et al.·Psychiatry investigation·2009

This study tested whether a medication called galantamine, which increases a brain chemical called acetylcholine, could help ME/CFS patients by improving hormone imbalances. Researchers measured two stress hormones (cortisol and DHEAS) in 29 ME/CFS patients before and after 4 weeks of treatment, comparing them to healthy controls. They found that in patients who improved with the medication, the abnormal hormone levels shifted back toward normal, suggesting the cholinergic system may play a role in ME/CFS.

Endocrine Disruption

E3 PreliminaryReviewPEM not requiredReview-Narrative

Chronic fatigue syndrome and the central nervous system.

Chen, R, Liang, F X, Moriya, J et al.·The Journal of international medical research·2008

This review examined brain imaging studies and blood tests in ME/CFS patients to understand how the illness affects the brain and nervous system. Researchers found evidence that ME/CFS patients show structural and functional differences in their brains, and that certain brain chemicals and immune molecules are abnormal. The authors suggest that future ME/CFS research should focus more on understanding how the central nervous system is involved in this illness.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

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

Tanriverdi, F, Karaca, Z, Unluhizarci, K et al.·Stress (Amsterdam, Netherlands)·2007

This review examines how the stress response system (called the HPA axis) works differently in people with ME/CFS and fibromyalgia. The HPA axis is normally responsible for managing how your body responds to stress. Most studies show that in these conditions, the system is underactive and produces lower levels of cortisol (a stress hormone), though some studies have found different results.

Endocrine Disruption

E3 PreliminaryCommentaryPEM not requiredEditorial

Drug residues store in the body following cessation of use: impacts on neuroendocrine balance and behavior--use of the Hubbard sauna regimen to remove toxins and restore health.

Cecchini, Marie, LoPresti, Vincent·Medical hypotheses·2007

This paper proposes that medications and drugs can accumulate in body fat over time and potentially cause long-term health problems even after someone stops taking them. The authors suggest that a treatment program involving exercise, sauna use, and vitamins might help remove these stored substances from the body and improve symptoms in conditions like ME/CFS.

Endocrine Disruption

E3 PreliminaryMechanismPEM not requiredCross-Sectional

Enhanced feedback sensitivity to prednisolone in chronic fatigue syndrome.

Jerjes, Walid K, Taylor, Norman F, Wood, Peter J et al.·Psychoneuroendocrinology·2007

This study tested how the bodies of ME/CFS patients respond to a small dose of a steroid medication called prednisolone. Researchers found that people with ME/CFS showed a stronger suppression of cortisol (a stress hormone) after taking the medication compared to healthy controls, suggesting their bodies may be overly sensitive to this type of feedback signal from the steroid.

Endocrine Disruption

E3 PreliminaryMechanismPEM not requiredMechanistic

Antidepressant-like activity of a Kampo (Japanese herbal) medicine, Koso-san (Xiang-Su-San), and its mode of action via the hypothalamic-pituitary-adrenal axis.

Ito, N, Nagai, T, Yabe, T et al.·Phytomedicine : international journal of phytotherapy and phytopharmacology·2006

This study tested whether Koso-san, a traditional Japanese herbal medicine, could help reduce depression-like symptoms in mice exposed to stress. Mice given Koso-san showed improved behavior in stress tests, and the herb appeared to normalize stress hormone systems in their brains that were overactive due to the stress exposure.

Endocrine Disruption

E3 PreliminaryReviewPEM not requiredReview-Narrative

[Chronic fatigue syndrome in cardiology neurohumoral changes].

Iasiukiavichene, L, Vasiliauskas, D·Kardiologiia·2006

This review examines why people with heart disease often experience severe fatigue and how the body's stress response system may be involved. The authors explain that chronic fatigue is a condition affecting the immune system, hormones, and nervous system, and can be triggered by stress, surgery, infections, or other illnesses. They suggest that measuring a stress hormone called cortisol could help doctors identify and treat fatigue in heart patients.

Endocrine Disruption

E3 PreliminaryMechanismPEM unclearCross-Sectional

Polymorphisms in genes regulating the HPA axis associated with empirically delineated classes of unexplained chronic fatigue.

Smith, Alicia K, White, Peter D, Aslakson, Eric et al.·Pharmacogenomics·2006

This study looked at whether different genetic variations in the stress-response system (HPA axis) and mood-related brain chemistry might explain why ME/CFS affects people differently. Researchers identified five distinct subgroups of people with chronic fatigue and found that three of these groups had different versions of specific genes compared to healthy people, suggesting that ME/CFS may not be one disease but rather several different conditions with different underlying genetic causes.

Endocrine Disruption

E3 PreliminaryCohortPEM not requiredCase-Control

Combinations of single nucleotide polymorphisms in neuroendocrine effector and receptor genes predict chronic fatigue syndrome.

Goertzel, Benjamin N, Pennachin, Cassio, de Souza Coelho, Lucio et al.·Pharmacogenomics·2006

Researchers looked at genetic variations (called SNPs) in genes related to stress hormones and brain chemistry to see if they could predict who has ME/CFS. Using patterns from 28 specific genetic variants, they correctly identified ME/CFS in about 76% of patients tested. This suggests that genetics play a role in ME/CFS, though genes are not the whole story.

Endocrine Disruption

E3 PreliminaryReviewPEM unclearReview-Narrative

A new view on hypocortisolism.

Fries, Eva, Hesse, Judith, Hellhammer, Juliane et al.·Psychoneuroendocrinology·2005

Some people with ME/CFS, fibromyalgia, and PTSD have abnormally low levels of cortisol, a stress hormone their body normally produces. This review suggests that this low cortisol may develop after the body's stress system works overtime for a long time. Interestingly, while low cortisol contributes to symptoms like fatigue, pain, and stress sensitivity, it may also provide some protective benefits to the body.

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.