Skip to content
← Research Hub
Endocrine

Endocrine Disruption

130 studies in the atlas

The hypothalamic-pituitary-adrenal (HPA) axis has been extensively studied in ME/CFS. A consistent pattern of mild hypocortisolism, attenuated diurnal cortisol variation, enhanced negative feedback, and blunted HPA axis responsiveness has been documented across multiple studies. These neuroendocrine findings are associated with worse symptoms and poorer treatment outcomes in clinical studies. HPA axis dysfunction may reflect dysregulation at the level of the central nervous system, the adrenal cortex, or both, and may interact with the immune and autonomic abnormalities observed in the illness.

What we know

  • Some studies have reported blunted cortisol responses and altered HPA axis function in ME/CFS
  • Thyroid function abnormalities have been observed in subsets of patients, though most have normal standard thyroid tests
  • Sex-specific differences in ME/CFS prevalence suggest hormonal factors may play a role
  • Endocrine findings are generally subtle and not consistent across studies

What remains uncertain

  • Whether HPA axis changes are a primary feature or a secondary adaptation to chronic illness
  • Whether subclinical thyroid dysfunction contributes meaningfully to symptoms
  • The role of sex hormones in the 2-4x higher prevalence of ME/CFS in women
  • Whether hormonal interventions could benefit specific patient subgroups

What is emerging

  • The mechanisms linking endocrine function to immune and metabolic abnormalities in ME/CFS
  • Whether endocrine profiles predict disease trajectory
  • The interaction between endocrine disruption and autonomic dysfunction
  • Whether menstrual cycle-related symptom fluctuations reflect underlying endocrine mechanisms

Start here

E0 ConsensusPEM not requiredModerate confidence

Research progress in the treatment of chronic fatigue syndrome through interventions targeting the hypothalamus-pituitary-adrenal axis.

Zhang, Yi-Dan, Wang, Li-Na·Frontiers in endocrinology·2024

This review examines how ME/CFS affects the body's stress-response system, called the HPA axis, which controls cortisol (a stress hormone). Research shows that people with ME/CFS tend to have lower cortisol levels, less natural variation in cortisol throughout the day, and a weaker response to stress compared to healthy people. Understanding these hormone changes may help explain why ME/CFS patients experience extreme fatigue and other symptoms, and could guide new treatments.

Research Momentum

130 publications over 32 years. Recent trend: steady (2/year over the last 3 years).

All Studies

130 studies, sorted by review status and evidence level

E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Research progress in the treatment of chronic fatigue syndrome through interventions targeting the hypothalamus-pituitary-adrenal axis.

Zhang, Yi-Dan, Wang, Li-Na·Frontiers in endocrinology·2024

This review examines how ME/CFS affects the body's stress-response system, called the HPA axis, which controls cortisol (a stress hormone). Research shows that people with ME/CFS tend to have lower cortisol levels, less natural variation in cortisol throughout the day, and a weaker response to stress compared to healthy people. Understanding these hormone changes may help explain why ME/CFS patients experience extreme fatigue and other symptoms, and could guide new treatments.

Endocrine Disruption
E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

Potential causal factors of CFS/ME: a concise and systematic scoping review of factors researched.

Muller, Ashley Elizabeth, Tveito, Kari, Bakken, Inger Johanne et al.·Journal of translational medicine·2020

Researchers reviewed over 1,100 studies published between 1979 and 2019 to understand what might cause ME/CFS. They found that scientists have studied many different potential causes, including immune system problems, psychological factors, infections, and hormonal imbalances. However, most of these studies were small and only suggested ideas rather than proving what actually causes ME/CFS—we need larger, better-designed studies to get real answers.

Endocrine Disruption
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome.

Tomas, Cara, Newton, Julia, Watson, Stuart·ISRN neuroscience·2013

This review examined how ME/CFS affects the HPA axis, a system in the brain that controls stress hormones like cortisol. Researchers found that many ME/CFS patients have problems with this system, including lower cortisol levels and changes in how their bodies respond to stress. The review suggests that genetics, past trauma, and oxidative stress may play a role, and notes that women are more commonly affected than men.

Endocrine Disruption
E0 ConsensusPEM not requiredPreliminarySystematic-ReviewEditor reviewed

Unstimulated cortisol secretory activity in everyday life and its relationship with fatigue and chronic fatigue syndrome: a systematic review and subset meta-analysis.

Powell, Daniel J H, Liossi, Christina, Moss-Morris, Rona et al.·Psychoneuroendocrinology·2013

This review looked at whether cortisol levels (a stress hormone) measured in saliva throughout the day are different in people with ME/CFS compared to healthy controls. Researchers found that people with ME/CFS showed a slightly smaller increase in cortisol when they first wake up, compared to healthy people. However, total cortisol levels during the day were not consistently related to how fatigued people felt.

Endocrine Disruption
E0 ConsensusPEM unclearPreliminaryReview-NarrativeEditor reviewed

Sleep abnormalities in chronic fatigue syndrome/myalgic encephalomyelitis: a review.

Jackson, Melinda L, Bruck, Dorothy·Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine·2012

People with ME/CFS often complain of sleep that doesn't feel refreshing, even when they sleep for normal or long amounts of time. This review looked at research studies measuring sleep in ME/CFS patients and found that standard sleep tests usually don't show obvious differences between patients and healthy people. However, newer, more detailed measurement techniques are beginning to reveal subtle sleep problems that standard tests miss.

Endocrine Disruption
E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

Hypothalamic-pituitary-adrenal axis dysfunction in chronic fatigue syndrome.

Papadopoulos, Andrew S, Cleare, Anthony J·Nature reviews. Endocrinology·2011

ME/CFS patients often have abnormal levels of cortisol, a stress hormone produced by the body. This review found that people with ME/CFS tend to have lower cortisol levels than healthy people, with less variation throughout the day and a weaker response to stress. These hormone changes are linked to worse symptoms and disability, and treatments like cognitive behavioral therapy may help restore more normal cortisol levels.

Endocrine Disruption
E0 ConsensusPEM not requiredPreliminarySystematic-ReviewEditor reviewed

The genetics and epigenetics of fatigue.

Landmark-Høyvik, Hege, Reinertsen, Kristin V, Loge, Jon H et al.·PM & R : the journal of injury, function, and rehabilitation·2010

This study reviewed scientific literature to understand whether genetics (inherited traits) and epigenetics (chemical changes that affect how genes work) influence fatigue in people with ME/CFS and other conditions. The researchers found that while some biological systems appear to malfunction in people with persistent fatigue, no clear genetic or epigenetic markers have been reliably identified yet. The authors argue that future research needs to be larger, better-designed, and consider how genes, environment, and body systems work together.

Endocrine DisruptionBiomarkers
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

Hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome.

Van Den Eede, Filip, Moorkens, Greta, Van Houdenhove, Boudewijn et al.·Neuropsychobiology·2007

This review examined research on the stress-response system (called the HPA axis) in ME/CFS patients. Scientists found that many people with ME/CFS have lower-than-normal stress hormone levels and don't respond typically to stress. While it's unclear whether this hormone imbalance causes ME/CFS or develops because of it, the authors suggest it likely plays a role in how symptoms develop and persist.

Endocrine Disruption
E0 ConsensusPEM not requiredModerate confidenceEditorialEditor reviewed

[Chronic fatigue syndrome--a functional somatic syndrome].

Linde, Andreas·Therapeutische Umschau. Revue therapeutique·2007

This review suggests that ME/CFS is a condition involving multiple body systems rather than a single cause, and that it shares features with other similar illnesses affecting the mind and body. The authors found that treatments involving gradual increases in activity and cognitive behavioral therapy show the most promise, while antidepressants may help as an add-on treatment.

Endocrine Disruption
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

The neuroendocrinology of chronic fatigue syndrome.

Cleare, Anthony J·Endocrine reviews·2003

This review examined how hormones—particularly the stress hormone cortisol and others made by the brain and glands—may be altered in ME/CFS patients. The researchers found that some patients have lower cortisol levels than expected, and their bodies may respond differently to stress, but these changes vary significantly from person to person. The review suggests that many factors like inactivity, poor sleep, and ongoing stress likely contribute to these hormone changes rather than a single cause.

Endocrine Disruption
E0 ConsensusPEM not requiredModerate confidenceReview-NarrativeEditor reviewed

The neuroendocrinology of chronic fatigue syndrome and fibromyalgia.

Parker, A J, Wessely, S, Cleare, A J·Psychological medicine·2001

This review examined how hormones and brain chemicals differ in ME/CFS patients. Researchers found that some patients have lower stress hormone (cortisol) levels, and their bodies show unusual patterns in serotonin and other brain chemical systems when tested. However, the findings were inconsistent across studies, and it's still unclear whether these changes cause ME/CFS symptoms or result from living with the illness.

Endocrine Disruption
E0 ConsensusPEM not requiredModerate confidenceMeta-AnalysisEditor reviewed

Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders.

Tak, Lineke M, Cleare, Anthony J, Ormel, Johan et al.·Biological psychology·2011

This research reviewed 85 studies examining whether people with ME/CFS, fibromyalgia, and irritable bowel syndrome have lower levels of the stress hormone cortisol. The researchers found that ME/CFS patients do have lower cortisol levels compared to healthy people, though the difference was modest. Being female also predicted lower cortisol, particularly in fibromyalgia patients.

Endocrine Disruption
E0 ConsensusPEM not requiredPreliminaryReview-NarrativeEditor reviewed

[Overlap between atypical depression, seasonal affective disorder and chronic fatigue syndrome].

Juruena, Mario Francisco, Cleare, Anthony James·Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)·2007

This review article examines whether ME/CFS, atypical depression, and seasonal affective disorder share common biological roots. The researchers found that all three conditions may involve underactivity in the body's stress-response system (particularly a part of the brain called the hypothalamic-pituitary-adrenal axis), rather than overactivity as seen in other types of depression. This suggests these conditions might be more closely related than previously thought, which could help explain why patients sometimes experience overlapping symptoms.

Endocrine Disruption
E0 ConsensusPEM unclearModerate confidenceSystematic-ReviewEditor reviewed

The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders.

Heim, C, Ehlert, U, Hellhammer, D H·Psychoneuroendocrinology·2000

This review examines why some people under chronic stress or after trauma have abnormally low levels of the stress hormone cortisol—a condition called hypocortisolism. The authors found that low cortisol appears in several conditions including ME/CFS, fibromyalgia, and rheumatoid arthritis, not just in PTSD. They propose that persistently low cortisol may make people more vulnerable to developing stress-related illnesses.

Endocrine Disruption
E0 ConsensusPEM not requiredModerate confidenceSystematic-ReviewEditor reviewed

[Neuro-endocrine correlates of burnout].

Verhaeghe, J, Van Den Eede, F, Van Den Ameele, H et al.·Tijdschrift voor psychiatrie·2012

Burnout, depression, and ME/CFS can feel similar, but they work differently in the body. This review looked at how burnout affects the stress hormone system (HPA-axis). Unlike depression, which over-activates this system, burnout appears to weaken it—similar to what happens in ME/CFS. The researchers found that people with burnout have lower stress hormone responses, suggesting burnout is more like exhaustion than depression.

Endocrine Disruption
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Disease mechanisms and clonidine treatment in adolescent chronic fatigue syndrome: a combined cross-sectional and randomized clinical trial.

Sulheim, Dag, Fagermoen, Even, Winger, Anette et al.·JAMA pediatrics·2014

This study looked at whether adolescents with ME/CFS have overactive stress response systems in their bodies and whether a medication called clonidine could help. Researchers found that young people with ME/CFS did have higher levels of stress chemicals and signs of body inflammation compared to healthy teens, but the medication did not improve their condition and actually reduced their physical activity. The study suggests that the overactive stress response may be the body's attempt to cope with ME/CFS rather than the root cause.

Endocrine Disruption
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Levels of DHEA and DHEAS and responses to CRH stimulation and hydrocortisone treatment in chronic fatigue syndrome.

Cleare, A J, O'Keane, V, Miell, J P·Psychoneuroendocrinology·2004

This study looked at stress hormone levels in people with ME/CFS, specifically a hormone called DHEA that affects mood, memory, and sleep. Researchers compared 16 ME/CFS patients to 16 healthy controls and tested how their bodies responded to a hormone challenge. They also gave some patients a low-dose steroid medication for a month to see if it helped. The findings suggest that DHEA levels are higher in ME/CFS and may relate to how disabled patients feel, and that low-dose steroid treatment can lower these levels and improve symptoms in some patients.

Endocrine Disruption
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Hypothalamo-pituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy.

Cleare, A J, Miell, J, Heap, E et al.·The Journal of clinical endocrinology and metabolism·2001

This study examined whether ME/CFS patients have problems with their stress hormone system (called the HPA axis) and whether a low dose of the steroid hormone hydrocortisone could help. Researchers found that ME/CFS patients had lower levels of cortisol (a stress hormone) in their urine and a reduced response to certain hormone challenges, suggesting their adrenal glands may not be producing enough cortisol. When some patients received hydrocortisone treatment, their fatigue improved and their hormone responses normalized.

Endocrine Disruption
E1 ReplicatedPEM not requiredModerate confidenceRCTEditor reviewed

Low-dose hydrocortisone for treatment of chronic fatigue syndrome: a randomized controlled trial.

McKenzie, R, O'Fallon, A, Dale, J et al.·JAMA·1998

Researchers tested whether low-dose hydrocortisone (a steroid hormone) could help ME/CFS patients by addressing a potential hormone imbalance in the body. Over 12 weeks, patients taking hydrocortisone showed somewhat more improvement in overall wellness compared to those taking placebo, but the difference was small and not quite statistically significant. However, the treatment caused the body's ability to produce its own cortisol to be suppressed in 12 patients, which made doctors decide the risks were too high to recommend this treatment.

Endocrine Disruption
E1 ReplicatedPEM unclearModerate confidenceRCTEditor reviewed

Lower hair cortisol concentration in adolescent and young adult patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Q-Fever Fatigue Syndrome compared to controls.

Vroegindeweij, Anouk, Eijkelkamp, Niels, van den Berg, Sjoerd A A et al.·Psychoneuroendocrinology·2024

This study looked at cortisol (a stress hormone) levels in hair samples from young people with ME/CFS and other fatigue conditions. Researchers found that people with ME/CFS and Q-Fever Fatigue Syndrome had lower cortisol levels in their hair compared to healthy people, suggesting a long-term difference in how their bodies handle this hormone. Interestingly, baseline cortisol levels did not predict whether patients would improve with lifestyle and dietary changes.

Endocrine Disruption
E2 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

Clinical characteristics of patients with unexplainable hypothalamic disorder diagnosed by the corticotropin-releasing hormone challenge test: a retrospective study.

Hataya, Yuji, Okubo, Marie, Hakata, Takuro et al.·BMC endocrine disorders·2022

Researchers used a special hormone test (CRH challenge test) to study a group of young women with chronic fatigue who had unusual patterns in their stress hormone system. They found that these patients had a mild form of adrenal insufficiency—their bodies weren't producing quite enough cortisol—but giving them cortisol supplements only helped some of them feel less fatigued. This suggests that their fatigue might involve more than just low cortisol levels.

Endocrine Disruption
E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

Glucocorticoid receptor DNA methylation and childhood trauma in chronic fatigue syndrome patients.

Vangeel, Elise Beau, Kempke, Stefan, Bakusic, Jelena et al.·Journal of psychosomatic research·2018

This study looked at chemical changes (called methylation) on genes that control how the body handles stress in people with ME/CFS compared to healthy controls. The researchers found small but consistent differences in a stress-response gene, particularly in patients who had experienced childhood trauma. While the differences were tiny (about 1-2%), they suggest that ME/CFS may involve changes in how the body's stress system works.

Endocrine Disruption
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Neuroendocrine disorder in chronic fatigue syndrome.

Tomic, Slavica, Brkic, Snezana, Lendak, Dajana et al.·Turkish journal of medical sciences·2017

This study looked at hormone levels in 40 women with ME/CFS compared to 40 healthy women to see if hormonal imbalances might explain ME/CFS symptoms. While standard hormone tests showed mostly normal results, researchers found that cortisol (a stress hormone) didn't follow its natural daily rhythm in ME/CFS patients the way it does in healthy people, and thyroid hormone T3 was lower in the ME/CFS group. The findings suggest that ME/CFS may involve subtle disruptions in how the body regulates these hormones over time.

Endocrine Disruption
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Self-critical perfectionism predicts lower cortisol response to experimental stress in patients with chronic fatigue syndrome.

Kempke, Stefan, Luyten, Patrick, Mayes, Linda C et al.·Health psychology : official journal of the Division of Health Psychology, American Psychological Association·2016

This study looked at whether people with ME/CFS who tend to be hard on themselves and set unrealistically high standards (self-critical perfectionism) have a different stress response than others. Researchers gave 41 women with ME/CFS a stressful test and measured their cortisol (a stress hormone) levels. They found that those with higher self-critical perfectionism felt more stressed mentally, but their bodies produced less cortisol in response—suggesting their stress system isn't working as well as it should.

Endocrine Disruption
E2 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

Chronic Fatigue Syndrome and DNA Hypomethylation of the Glucocorticoid Receptor Gene Promoter 1F Region: Associations With HPA Axis Hypofunction and Childhood Trauma.

Vangeel, Elise, Van Den Eede, Filip, Hompes, Titia et al.·Psychosomatic medicine·2015

This study looked at a chemical marker called DNA methylation on a gene (NR3C1) that controls how the body responds to stress. Researchers found that people with ME/CFS had lower levels of this methylation compared to healthy people, which may explain why their bodies don't handle stress hormones properly. Interestingly, childhood trauma did not appear to create additional changes in this marker among ME/CFS patients.

Endocrine Disruption
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Effects of early childhood trauma on hypothalamic-pituitary-adrenal (HPA) axis function in patients with Chronic Fatigue Syndrome.

Kempke, Stefan, Luyten, Patrick, De Coninck, Sarah et al.·Psychoneuroendocrinology·2015

This study looked at whether traumatic experiences in childhood are connected to how the body's stress system (the HPA axis) works in people with ME/CFS. Researchers measured stress hormone levels in 40 women with ME/CFS and tested how their bodies responded to stress. They found that emotional neglect in childhood was linked to a blunted (reduced) stress response, suggesting that some ME/CFS patients may have a stress system that doesn't react normally to challenges.

Endocrine Disruption
E2 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

Cortisol output in adolescents with chronic fatigue syndrome: pilot study on the comparison with healthy adolescents and change after cognitive behavioural guided self-help treatment.

Rimes, Katharine A, Papadopoulos, Andrew S, Cleare, Anthony J et al.·Journal of psychosomatic research·2014

This study measured stress hormone (cortisol) levels in teenagers with ME/CFS compared to healthy teenagers. Teenagers with ME/CFS had lower cortisol levels throughout the day than healthy peers. After cognitive behavioural treatment, cortisol levels in the ME/CFS group returned to normal, suggesting the hormonal difference may be reversible.

Endocrine Disruption
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction.

Heim, Christine, Nater, Urs M, Maloney, Elizabeth et al.·Archives of general psychiatry·2009

This study found that people with ME/CFS who experienced childhood trauma (such as abuse or neglect) have significantly different stress hormone levels compared to healthy people. Specifically, those with ME/CFS and childhood trauma history showed lower cortisol (a stress hormone) levels after waking up. The research suggests that early difficult experiences may damage the body's stress-response system in ways that increase vulnerability to developing ME/CFS later in life.

Endocrine Disruption
E2 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

Glucocorticoid receptor mediated negative feedback in chronic fatigue syndrome using the low dose (0.5 mg) dexamethasone suppression test.

Papadopoulos, Andrew, Ebrecht, Marcel, Roberts, Amanda D L et al.·Journal of affective disorders·2009

This study looked at how the body's stress hormone system works in ME/CFS patients. Researchers gave a small dose of a synthetic hormone called dexamethasone to 18 ME/CFS patients and 20 healthy people, then measured how much their natural stress hormone (cortisol) decreased in response. Interestingly, ME/CFS patients who also had depression showed a larger drop in cortisol than healthy controls, suggesting their feedback system may be working overtime.

Endocrine Disruption
E2 ModeratePEM not requiredPreliminaryLongitudinalEditor reviewed

Salivary cortisol output before and after cognitive behavioural therapy for chronic fatigue syndrome.

Roberts, Amanda D L, Papadopoulos, Andrew S, Wessely, Simon et al.·Journal of affective disorders·2009

This study looked at whether cognitive behavioural therapy (CBT)—a type of talk therapy—could help fix a hormone imbalance found in ME/CFS patients. Researchers measured a stress hormone called cortisol in the saliva of 41 patients before and after 15 sessions of CBT. They found that cortisol levels increased after therapy, suggesting that CBT may help restore this hormone to healthier levels.

Endocrine Disruption
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Chronic fatigue syndrome and high allostatic load: results from a population-based case-control study in Georgia.

Maloney, Elizabeth M, Boneva, Roumiana, Nater, Urs M et al.·Psychosomatic medicine·2009

This study looked at whether people with ME/CFS have higher levels of 'allostatic load'—a measure of how much stress and wear-and-tear their bodies have accumulated over time. Researchers compared 83 people with ME/CFS, 202 people with some symptoms but not full ME/CFS, and 109 healthy controls in Georgia. They found that people with ME/CFS did have significantly higher allostatic load than healthy people, suggesting their bodies may be under greater physiological stress.

Endocrine Disruption
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls.

Nater, Urs M, Maloney, Elizabeth, Boneva, Roumiana S et al.·The Journal of clinical endocrinology and metabolism·2008

This study looked at cortisol, a hormone released by the body in the morning to help us wake up and manage stress. Researchers compared cortisol levels in people with ME/CFS to healthy people and found that ME/CFS patients, especially women, had lower morning cortisol levels than expected. This suggests the hormone system that controls cortisol may not be working normally in ME/CFS.

Endocrine Disruption
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Combined dexamethasone/corticotropin-releasing factor test in chronic fatigue syndrome.

Van Den Eede, F, Moorkens, G, Hulstijn, W et al.·Psychological medicine·2008

This study tested how well the stress-response system (HPA axis) works in ME/CFS patients compared to healthy people. Researchers gave patients a special test involving two hormones and measured cortisol levels in saliva. They found that ME/CFS patients had lower cortisol responses than healthy controls, suggesting their stress-response system may not be working properly—but this was especially true for patients without a history of childhood trauma.

Endocrine Disruption
E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

Glucocorticoid receptor polymorphisms and haplotypes associated with chronic fatigue syndrome.

Rajeevan, M S, Smith, A K, Dimulescu, I et al.·Genes, brain, and behavior·2007

This study looked at whether differences in a specific gene (the glucocorticoid receptor gene) might affect who develops ME/CFS. Researchers compared 40 people with ME/CFS to people without the illness and found that certain genetic variations were more common in those with ME/CFS. This gene is involved in how the body manages stress through a system called the HPA axis, which may be disrupted in ME/CFS.

Endocrine Disruption
E2 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

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 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

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 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

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 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

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 ModeratePEM unclearModerate confidenceCross-SectionalEditor reviewed

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 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

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 ModeratePEM unclearModerate confidenceCase-ControlEditor reviewed

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 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

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 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

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 ModeratePEM not requiredPreliminaryObservationalEditor reviewed

[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 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

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 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

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 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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 ModeratePEM not requiredModerate confidenceObservationalEditor reviewed

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 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

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 ModeratePEM not requiredModerate confidenceMechanisticEditor reviewed

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 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

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 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

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 ModeratePEM unclearPreliminaryCross-SectionalEditor reviewed

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 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

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 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

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 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

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 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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 ModeratePEM not requiredPreliminaryMechanisticEditor reviewed

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 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

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 ModeratePEM not requiredModerate confidenceCase-ControlEditor reviewed

Cortisol levels in chronic fatigue syndrome and atypical depression measured using hair and saliva specimens.

Herane-Vives, Andres, Papadopoulos, Andrew, de Angel, Valeria et al.·Journal of affective disorders·2020

This study compared stress hormone (cortisol) levels in people with ME/CFS and people with a specific type of depression called atypical depression, both with and without fatigue. Researchers measured cortisol in two ways: through hair samples (showing levels over 3 months) and saliva samples (showing daily patterns). Both ME/CFS and atypical depression groups had lower daily cortisol output than healthy people, but normal cortisol levels when measured over longer periods, suggesting the low levels might be temporary or related to how the body's rhythm changes.

Endocrine Disruption
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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 ModeratePEM not requiredPreliminaryCross-SectionalEditor reviewed

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 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

Hair cortisol levels in women with medically unexplained symptoms.

Fischer, Susanne, Skoluda, Nadine, Ali, Nida et al.·Journal of psychiatric research·2022

This study tested whether people with medically unexplained symptoms have different stress hormone levels than healthy people. Researchers measured cortisol (a stress hormone) in hair samples, which shows stress levels over the previous three months. They found that women with somatic symptom disorder (a condition involving excessive worry about physical symptoms) had lower cortisol than healthy women, but women with chronic fatigue syndrome, fibromyalgia, and irritable bowel syndrome did not differ from healthy controls.

Endocrine Disruption
E2 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

Diurnal pattern of cortisol output in postnatal depression.

Taylor, Alyx, Glover, Vivette, Marks, Maureen et al.·Psychoneuroendocrinology·2009

This study looked at how stress hormone (cortisol) levels change throughout the day in women with depression after having a baby, compared to women without postpartum depression and non-pregnant women. The researchers found that depressed women had unusually high cortisol levels when they woke up and didn't show the normal increase in cortisol that typically happens 30 minutes after waking, which is similar to patterns seen in chronic fatigue syndrome.

Endocrine Disruption
E2 ModeratePEM not requiredPreliminaryCase-ControlEditor reviewed

Reduced plasma dehydroepiandrosterone sulfate levels are significantly correlated with fatigue severity in patients with primary biliary cirrhosis.

Ahboucha, Samir, Pomier-Layrargues, Gilles, Vincent, Catherine et al.·Neurochemistry international·2008

This study looked at a hormone called DHEAS in patients with a liver disease called primary biliary cirrhosis (PBC). The researchers found that patients with PBC who experienced fatigue had lower DHEAS levels than healthy people, and the lower the DHEAS, the more severe their fatigue was. This suggests that low DHEAS might be one reason why some liver patients feel exhausted, and raising DHEAS levels might help reduce their fatigue.

Endocrine Disruption
E2 ModeratePEM not requiredModerate confidenceLongitudinalEditor reviewed

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 ModeratePEM not requiredModerate confidenceCross-SectionalEditor reviewed

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
E3 PreliminaryPEM unclearPreliminaryMechanisticEditor reviewed

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 PreliminaryPEM unclearPreliminaryMethods-PaperEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearPreliminaryMechanisticEditor reviewed

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
E3 PreliminaryPEM not requiredPreliminaryMethods-PaperEditor reviewed

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 PreliminaryPEM unclearPreliminaryMethods-PaperEditor reviewed

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 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

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 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

[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 PreliminaryPEM unclearPreliminaryObservationalEditor reviewed

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 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

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 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredPreliminaryEditorialEditor reviewed

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 PreliminaryPEM unclearModerate confidenceReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredModerate confidenceCross-SectionalEditor reviewed

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 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

[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 PreliminaryPEM unclearPreliminaryCross-SectionalEditor reviewed

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 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

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 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredModerate confidenceCross-SectionalEditor reviewed

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 PreliminaryPEM unclearPreliminaryEditorialEditor reviewed

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 PreliminaryPEM not requiredPreliminaryRCTEditor reviewed

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 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredModerate confidenceObservationalEditor reviewed

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 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

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 PreliminaryPEM not requiredPreliminaryObservationalEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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.

Endocrine DisruptionPain and Sensitization
E3 PreliminaryPEM not requiredModerate confidenceMechanisticEditor reviewed

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
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

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 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Neuroendocrine correlates of chronic fatigue syndrome: a brief review.

Demitrack, M A·Journal of psychiatric research·1997

This review examines how ME/CFS might be connected to problems with the body's stress hormone system and brain chemistry. Researchers found that people with ME/CFS often have a specific pattern of disruption in their stress response system—different from what occurs in depression—along with changes in serotonin levels. These findings suggest that ME/CFS involves real biological changes, not just psychological factors.

Endocrine Disruption
E3 PreliminaryPEM not requiredPreliminaryCase-ControlEditor reviewed

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

Dinan, T G, Majeed, T, Lavelle, E et al.·Psychoneuroendocrinology·1997

This study tested whether a specific brain chemical system called serotonin works properly in ME/CFS patients. Researchers gave patients and healthy people a medication that activates serotonin receptors, then measured how the body's stress-response system (the HPA axis) reacted. They found that ME/CFS patients had a weaker response than healthy people, suggesting this brain system doesn't function normally in ME/CFS.

Endocrine Disruption
E3 PreliminaryPEM not requiredPreliminaryCross-SectionalEditor reviewed

Increased prolactin response to buspirone in chronic fatigue syndrome.

Sharpe, M, Clements, A, Hawton, K et al.·Journal of affective disorders·1996

Researchers gave a medication called buspirone to people with ME/CFS and healthy volunteers to see how their bodies would respond. People with ME/CFS had higher levels of a hormone called prolactin and experienced more nausea than the healthy group. This suggests that the brains of people with ME/CFS may process certain chemicals differently, particularly those involved in mood and nerve signaling.

Endocrine Disruption
E3 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

Neuroendocrine responses to d-fenfluramine and insulin-induced hypoglycemia in chronic fatigue syndrome.

Bearn, J, Allain, T, Coskeran, P et al.·Biological psychiatry·1995

This study tested whether ME/CFS might be caused by problems with the brain's hormone-control system (the pituitary and adrenal glands). Researchers gave patients and healthy people two different tests—one using low blood sugar and another using a serotonin-stimulating drug—to measure hormone responses. They found that ME/CFS patients had unusual patterns in some hormones, suggesting their glands may not be working normally.

Endocrine Disruption
E3 PreliminaryPEM not requiredPreliminaryObservationalEditor reviewed

Plasma and cerebrospinal fluid monoamine metabolism in patients with chronic fatigue syndrome: preliminary findings.

Demitrack, M A, Gold, P W, Dale, J K et al.·Biological psychiatry·1992

This study measured chemical messengers in the blood and spinal fluid of people with ME/CFS and compared them to healthy individuals. Researchers found that people with ME/CFS had lower levels of one chemical (MHPG, related to stress response) and higher levels of another (5-HIAA, related to mood regulation). These differences suggest ME/CFS may have biological markers that distinguish it from purely psychiatric conditions.

Endocrine Disruption
E3 PreliminaryPEM not requiredModerate confidenceMechanisticEditor reviewed

Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome.

Demitrack, M A, Dale, J K, Straus, S E et al.·The Journal of clinical endocrinology and metabolism·1991

This study examined whether ME/CFS patients have a problem with their body's stress hormone system, specifically the network that controls cortisol production. Researchers found that ME/CFS patients had lower cortisol levels than healthy people, but their bodies were responding unusually to stimulation—suggesting the problem lies in the brain's control center rather than the adrenal glands themselves.

Endocrine Disruption
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearPreliminaryMechanisticEditor reviewed

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 PreliminaryPEM unclearPreliminaryMechanisticEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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
E3 PreliminaryPEM not requiredModerate confidenceObservationalEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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 PreliminaryPEM unclearPreliminaryReview-NarrativeEditor reviewed

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.

Endocrine DisruptionPain and Sensitization
E3 PreliminaryPEM unclearModerate confidenceReview-NarrativeEditor reviewed

Evidence that abnormalities of central neurohormonal systems are key to understanding fibromyalgia and chronic fatigue syndrome.

Crofford, L J, Demitrack, M A·Rheumatic diseases clinics of North America·1996

This study explores how stress-response systems in the brain and body may be broken in people with fibromyalgia and chronic fatigue syndrome (ME/CFS). Both conditions often start after stressful events and get worse during stressful times. The researchers found that the brain's main stress-management system—called the hypothalamic-pituitary-adrenal (HPA) axis—does not work normally in these patients, which could explain why their symptoms worsen with stress.

Endocrine Disruption
E3 PreliminaryPEM not requiredPreliminaryReview-NarrativeEditor reviewed

Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs.

Gold, P W, Licinio, J, Wong, M L et al.·Annals of the New York Academy of Sciences·1995

This research examines how the stress hormone system works differently in people with depression and chronic fatigue syndrome. The study found that while some people with depression have too much cortisol (a stress hormone), others—particularly those with fatigue-related conditions—may have too little activity in the part of the brain that normally triggers this hormone. This suggests that different types of depression and fatigue conditions might involve different problems with the body's stress response system.

Endocrine Disruption
E3 PreliminaryPEM unclearPreliminaryCase-ControlEditor reviewed

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 PreliminaryPEM unclearModerate confidenceReview-NarrativeEditor reviewed

Fatigue in neurological disorders.

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

This review examines fatigue in various neurological diseases, including ME/CFS. The authors explain that fatigue can result from problems in muscle function (where muscles can't sustain effort) or problems in the brain and nervous system (where the brain perceives activities as requiring excessive effort). They suggest that imbalances in stress hormones and disrupted communication between key brain regions may underlie persistent fatigue.

Endocrine Disruption
E3 PreliminaryPEM not requiredPreliminaryMechanisticEditor reviewed

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
E2 ModeratePEM unclearPreliminaryObservationalMachine-drafted

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
E3 PreliminaryPEM unclearPreliminaryCase-ControlMachine-drafted

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 abnormal hormone levels (low thyroid and adrenal hormones, but high cortisol) and brain imaging showing shrinkage of the brain's outer layer. When treated with a low dose of a medication called modafinil along with lifestyle changes, the patient's symptoms improved. The study highlights that ME/CFS can have measurable physical changes and that doctors need better tools to diagnose and treat this condition.

Endocrine Disruption
E3 PreliminaryPEM unclearPreliminaryMachine-drafted

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 PreliminaryPEM unclearPreliminaryReview-NarrativeMachine-drafted

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 PreliminaryPEM unclearPreliminaryObservationalMachine-drafted

Increased brain serotonin function in men with chronic fatigue syndrome.

Sharpe, M, Hawton, K, Clements, A et al.·BMJ (Clinical research ed.)·1997

This 1997 study examined whether people with ME/CFS have differences in serotonin activity in their brains. Serotonin is a chemical messenger that affects mood, sleep, and energy. The researchers found that men with ME/CFS showed increased brain serotonin function compared to healthy controls, which was unexpected since low serotonin is often associated with fatigue and depression.

Endocrine Disruption
E3 PreliminaryPEM unclearPreliminaryReview-NarrativeMachine-drafted

Chronic fatigue syndrome: a stress disorder?

Cleare, A J, Wessely, S C·British journal of hospital medicine·1996

This paper explores whether ME/CFS might be connected to stress and how the body responds to stress. The authors examine the evidence around the relationship between stress responses and ME/CFS symptoms, considering whether stress-related factors play a role in the condition's development or persistence.

Endocrine Disruption

Contribute

Private, reviewed by a human. Not a public comment thread.

Report an errorSuggest a sourceAsk a follow-upRequest a guide