Endometriosis and Myalgic Encephalomyelitis-Chronic Fatigue Syndrome Show Strong Epidemiologic Overlap

Evidence Points to Shared Immune Dysregulation Linking Endometriosis and Myalgic Encephalomyelitis-Chronic Fatigue Syndrome.

Key Points

Highlights: 

• Endometriosis is significantly associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), suggesting shared underlying inflammatory or immune mechanisms.euroendocrine mechanisms. 

Importance:

• Understanding the relationship underscores the need for integrated, multidisciplinary approaches for patients who present with overlapping symptoms of chronic pelvic pain, fatigue, and systemic inflammatory manifestations.

What’s done here:

• This is a systematic literature review and meta-analysis based on the studies evaluating the coexistence of endometriosis and ME/CFS.
• Databases were searched for observational studies reporting the prevalence or odds of ME/CFS in patients with endometriosis, or vice versa.
• Eligible studies underwent quality assessment, and pooled effect sizes were calculated to quantify the strength of association between the two conditions.
• 'Subgroup and sensitivity analyses were performed to evaluate consistency across study designs and populations.

Key results:

• Patients with endometriosis showed a 2.79-fold higher risk of developing ME/CFS compared with controls, demonstrating a strong epidemiologic association.
• The pooled odds ratio of 2.52 across included studies further confirmed a consistent link between the two conditions.
• Effect sizes remained stable across multiple sensitivity analyses, suggesting that the association is unlikely to be driven by any single study or methodological approach.

Strengths and Limitations:

• Strengths are, the use of a systematic review and meta-analytic approach, pooling data across multiple studies to generate a more precise estimate of the association; application of formal quality assessment tools; and consistency of findings across sensitivity analyses, which strengthens confidence in the observed association.
• Limitations are, the predominance of cross-sectional designs preventing causal inference; potential unmeasured confounders such as mood disorders, autoimmune conditions, and chronic pain syndromes; heterogeneity in diagnostic criteria for ME/CFS; and the overrepresentation of U.S.-based studies, which may limit global generalizability.

From the Editor-in-Chief – EndoNews

"The relationship between endometriosis and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has long been suspected but insufficiently defined. This meta-analysis provides one of the clearest quantitative evaluations to date, showing a more than twofold increased likelihood of ME/CFS among individuals with endometriosis. Although the included studies are limited in number and largely observational, the consistency of effect sizes across analyses suggests that the association is not incidental.

What makes these findings particularly compelling is that they align with a growing recognition that endometriosis is not only a gynecologic disorder but part of a broader landscape of chronic inflammatory and immune-mediated conditions. ME/CFS—which is characterized by profound fatigue, exertional intolerance, neuroimmune dysregulation, and autonomic disturbances—shares several biological features with endometriosis, including immune activation, altered cytokine signaling, mitochondrial stress, and dysregulated neuroendocrine pathways. The convergence of these mechanisms provides a plausible explanation for why the two conditions may co-occur more frequently than expected by chance.

The clinical implications of this overlap are significant. Patients with endometriosis who also report persistent, debilitating fatigue, cognitive slowing, unrefreshing sleep, or post-exertional symptom worsening may not be experiencing symptoms solely attributable to pelvic disease. The recognition of a potential ME/CFS phenotype in this population invites a more comprehensive approach to evaluation—one that integrates gynecologic, neurologic, immunologic, and autonomic assessment. Conversely, ME/CFS patients with pelvic pain, dysmenorrhea, or infertility may benefit from targeted evaluation for endometriosis.

Still, caution is warranted. The predominance of cross-sectional data limits causal inference, and unmeasured confounders such as depression, chronic pain sensitization, and autoimmune comorbidity may contribute to the association. Diagnostic criteria for ME/CFS also vary substantially across studies, adding noise to the underlying signal. Yet even within these constraints, the observed effect sizes are sufficiently robust to merit attention.

This work underscores the need for transdisciplinary research focused on shared inflammatory circuits, neuroimmune interactions, and mitochondrial–metabolic dysfunction that may bridge endometriosis and ME/CFS. Understanding these common pathways could ultimately advance therapeutics for both conditions—shifting the conversation from symptom management to mechanistic intervention.

For clinicians, the message is clear: when patients present with the combined burdens of chronic pelvic pain and chronic fatigue, a siloed approach to diagnosis and care is no longer adequate. This meta-analysis reinforces the importance of integrated, whole-person care for diseases that may intersect more deeply than previously recognized."

Lay Summary

A new study from researchers in Grenada suggests a significant association between endometriosis and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)—two chronic, debilitating conditions that share symptoms of inflammation, immune activation, and profound fatigue.

The research team, led by Dr. Prakash VAK Ramdass from the Department of Public Health and Preventive Medicine at St. George's University, conducted a systematic review and meta-analysis to clarify whether the two diseases tend to occur together more often than expected. Their analysis, published in the journal Diagnostics, included five studies involving a total of 2,261 participants.

Across all included studies, people with endometriosis were found to have a 2.79-fold higher risk of also having ME/CFS compared with individuals without endometriosis. When the data were pooled, the overall odds ratio was 2.52, indicating a consistent and clinically meaningful association. Importantly, statistical heterogeneity was minimal, strengthening confidence in the reliability of these findings.

ME/CFS is a chronic condition characterized by severe, persistent fatigue lasting six months or more, often accompanied by cognitive impairment, unrefreshing sleep, pain, and worsening of symptoms after activity. Although its exact cause remains unknown, both ME/CFS and endometriosis share features of immune dysregulation, chronic inflammation, and multisystem involvement, providing a biological basis for their overlap.

The authors note that these results highlight the importance of integrated, multidisciplinary care, as patients who live with both conditions often experience complex symptoms that span gynecologic, immune, neurologic, and systemic domains. Further research is needed to determine whether shared biological pathways directly link the two diseases or whether the association reflects broader patterns of chronic inflammatory illness.

Research Source: https://pubmed.ncbi.nlm.nih.gov/41008704/