Endometriosis Comorbidities: A Whole-Body Disease

Why Endometriosis Is More Than “Just a Gynecological Condition”

Endometriosis has long been treated as a condition limited to the pelvis and reproductive organs. However, growing research and lived patient experience tell a much broader story. Many people with endometriosis experience symptoms that affect the nervous system, immune system, and connective tissue, suggesting that endometriosis can be a whole-body condition.

These additional conditions are known as comorbidities—medical conditions that occur together more often than would be expected by chance. Importantly, not every person with endometriosis will experience or be diagnosed with these conditions, and research is still evolving.

Some links are well supported by scientific evidence, while others remain under investigation. Recognizing these patterns matters because it helps patients feel believed, understood, and more comprehensively cared for.

1. Neurological Manifestations

Migraine

Among all comorbidities, the link between migraine and endometriosis is one of the strongest and most consistently supported by research. People with endometriosis experience migraines at significantly higher rates than the general population.

Researchers believe this overlap may be explained by:

• Shared genetic susceptibility

• Hormonal fluctuations, particularly changes in estrogen signaling, which play a key role in endometriosis and also influence how the brain processes pain

Chronic Pain Conditions, Fibromyalgia, and Mood Disorders

Large population studies show that many people with endometriosis also experience:

• Chronic widespread pain

• Fibromyalgia

• Anxiety and depression

In a large study of over 10,000 people with endometriosis, more than one-third reported at least one additional chronic condition, often clustering around pain disorders, migraine, and mood conditions.

This supports the idea that for many patients, endometriosis exists within a broader pain sensitization and nervous system involvement, rather than as an isolated gynecological disease.

Higher rates of anxiety and depression may reflect both shared biological mechanisms and the significant impact of chronic pain, delayed diagnosis, and reduced quality of life.

2. Connective Tissue and Autonomic Conditions

Joint Hypermobility Disorders

(including hypermobile Ehlers-Danlos syndrome and Hypermobility Spectrum Disorders)

There is growing interest in the overlap between joint hypermobility disorders and endometriosis. Some studies suggest that people with endometriosis—particularly those with more advanced disease—may have higher rates of joint hypermobility than the general population.

Hypermobility conditions can cause:

• Pelvic pain

• Fatigue

• Gastrointestinal symptoms

Because these symptoms overlap with endometriosis, diagnosis can be more complex. While this relationship is actively being studied, it is not yet fully understood, and definitive conclusions cannot currently be drawn.

Postural Orthostatic Tachycardia Syndrome (POTS)

POTS affects the autonomic nervous system, which regulates heart rate and blood pressure, particularly when moving from sitting to standing.

Symptoms can include:

• Rapid heartbeat (tachycardia)

• Dizziness or fainting (syncope)

• Fatigue, brain fog, and headaches

Some people with endometriosis report fainting or worsening autonomic symptoms during menstruation or pain flares. Research exploring a direct link between POTS and endometriosis has produced mixed results, and no definitive association has been established.

What is clear is that hormonal fluctuations can influence POTS symptoms, which may explain why some patients notice symptom changes across their menstrual cycle.

3. Immune System Manifestations

Mast Cell Activation

Mast cells are immune cells involved in allergic reactions and inflammation. They are increasingly studied in endometriosis because:

• Mast cells are found in high numbers around endometriosis lesions

• They interact closely with estrogen, a key driver of endometriosis

• They may contribute to chronic pain and nerve sensitization

These findings have led researchers to explore possible overlaps with mast cell activation disorders, which can involve symptoms such as flushing, itching, digestive issues (including diarrhea), and systemic inflammation.

Hypermobility disorders, POTS, and mast cell disorders are sometimes discussed together as a “triad.” While many patients report experiencing these conditions together, this area remains under-researched, and no definitive causal link has been established. Patient experiences remain important in guiding future research priorities.

Asthma and Atopic Conditions

Asthma, allergic conditions, and atopic skin disorders appear more frequently in people with endometriosis, further supporting the idea that immune system involvement extends beyond the pelvis.

4. Autoimmunity and Inflammation

Endometriosis is increasingly described as a chronic, systemic inflammatory condition, rather than solely a gynecological disease.

Recent large-scale studies show that people with endometriosis have higher-than-average rates of certain autoimmune and inflammatory conditions, including:

• Rheumatoid arthritis

• Osteoarthritis

• Psoriasis

• Celiac disease

• Multiple sclerosis (to a lesser extent)

Genetic studies suggest shared risk pathways, particularly between endometriosis and rheumatoid arthritis. Understanding these overlaps may help guide future research into targeted treatments for inflammatory and autoimmune diseases.

Key Takeaways

• Endometriosis is increasingly recognized as a chronic, whole-body condition, not just a disorder of the reproductive organs.

• Some comorbidities—such as migraine and chronic pain conditions—are well supported by research.

• Others—including POTS, hypermobility disorders, and mast cell conditions—are biologically plausible but not yet definitively established.

• Many patients may benefit from multidisciplinary care that addresses pain, hormones, mental health, immune symptoms, and overall quality of life.

• Listening to patient experiences, alongside rigorous scientific research, is essential to improving care and outcomes.

References 

1. Hugon-Rodin J, et al. Human Reproduction. 2025;40(Suppl 1):deaf097.618.

2. Ferrero S, et al. Migraine and endometriosis: shared mechanisms. Cephalalgia. 2020;40(4):363–371.

3. Nappi RE, et al. Estrogen signaling and migraine in women. Front Neurol. 2024;15:12007130.

4. Chiaffarino F, et al. Joint hypermobility and endometriosis. Hum Reprod. 2016;31(5):1137–1144.

5. Tirlapur SA, et al. Autonomic dysfunction in chronic pelvic pain. J Pediatr Adolesc Gynecol. 2014;27(4):208–212.

6. Fuentes-Zacarias P, et al. Mast cells and estrogen-driven pain in endometriosis. Int J Biol Sci. 2025;21(12):5891–5904.

7. Shigesi N, et al. Autoimmune diseases and endometriosis risk. Hum Reprod. 2019;34(11):2232–2243.