Mast Cell Activation Syndrome and Endometriosis: A Potential Link to Unexplained Symptoms

Mast cell activation syndrome and endometriosis may overlap

Mast cell activation syndrome and endometriosis may be linked, potentially explaining overlapping or otherwise unexplained symptoms in some people. Having either condition does not mean you have the other. Mast cells found in endometriosis tissue may contribute to local inflammation, but their presence alone does not establish a diagnosis of mast cell activation syndrome (MCAS).

If you’d like a specialist’s view on your endometriosis symptoms or a recommended treatment, our team can help review your options. When MCAS is also a possibility, evaluation and treatment should be coordinated with a clinician experienced in mast cell disorders.

How mast cells may contribute to endometriosis symptoms

Mast cells are immune cells that release histamine and other inflammatory mediators, substances that trigger or regulate inflammation. MCAS is a disorder characterized by excessive activation of these cells. Reports have described elevated mast cells in endometriosis tissue in up to 80% of cases; that figure refers to tissue findings, not the percentage of people with endometriosis who have MCAS.

The proposed interaction works in both directions. Mast cells may promote the development and persistence of endometriosis by driving inflammation, new blood-vessel formation, and nerve growth. These processes may help lesions persist and contribute to pain.

Endometriotic lesions themselves may release factors that activate mast cells, including vascular endothelial growth factor, substance P, and nerve growth factor. This could create a cycle in which lesions activate mast cells and mast cell activity supports the lesions. It remains a proposed mechanism rather than proof that endometriosis causes MCAS.

Symptoms that may warrant a closer look at mast cell activation

In MCAS, mast cells can become hypersensitive to stress, environmental factors, or physical stimuli. Symptoms may include flushing, itching, diarrhea, abdominal pain, and shortness of breath. Abdominal symptoms can overlap with endometriosis, making it harder to identify what is driving them.

Considering MCAS in people with atypical or otherwise unexplained inflammatory symptoms may improve diagnostic accuracy and care. The pattern matters: which symptoms occur together, how quickly they develop, how long they last, and what precedes them. Symptom overlap alone is insufficient for diagnosis.

A 2025 clinical review of MCAS diagnosis and management, based mainly on findings in adults, describes consensus criteria requiring severe, recurrent episodes involving at least two organ systems, laboratory confirmation of mast cell activation, and a response to mast-cell-directed treatment. Evaluation also considers other explanations, including food allergy and reactions to nonsteroidal anti-inflammatory drugs.

Testing may involve comparing a baseline blood tryptase level with a sample obtained within four hours of an episode. Urinary mast cell mediator testing is another option in some circumstances. A high baseline result alone does not diagnose MCAS, and a normal baseline result does not rule it out.

Questions to take to your doctors include:

• Do my symptoms occur in episodes involving more than one organ system, or does another explanation fit better?
• Could stress, heat, exercise, food, medications, or environmental exposures be contributing?
• Would an evaluation for MCAS be appropriate, and how should any baseline and episode-related testing be arranged?

Treatment can address both conditions

Care should be personalized and multidisciplinary, with treatment directed at each condition and the symptoms it is causing. Symptom improvement has been reported in women with both MCAS and endometriosis treated with a combination of hormonal therapy and MCAS-directed therapies. This does not guarantee the same response for everyone.

MCAS-directed medications and trigger management

Medication options include antihistamines to block histamine’s effects, mast cell stabilizers to reduce mediator release, and leukotriene inhibitors to block another inflammatory pathway. The 2025 MCAS review describes starting preventive medication with H1-antihistamines for recurrent episodes and stepping up treatment as needed. Some people require more than one medication.

Lifestyle strategies include stress reduction, environmental trigger avoidance, dietary modification, and low-histamine diets. These measures should be tailored to the person’s triggers and nutritional needs rather than applied as a fixed plan for everyone. Ongoing management combines individualized medications with strategies to minimize mast cell degranulation, the release of inflammatory substances stored inside these cells.

Hormonal options for endometriosis

For endometriosis, reducing systemic inflammation and controlling lesion growth remain priorities. Commonly used hormonal options include combined oral contraceptives, GnRH agonists, and GnRH antagonists.

Some hormonal therapies carry notable long-term side effects, including bone density loss. Discuss how the expected benefits, treatment duration, and side-effect profile fit your circumstances, alongside the plan for managing MCAS.

Excision surgery requires individualized MCAS planning

What excision may and may not change

Excision surgery is considered the gold-standard surgical treatment for endometriosis, while its implications for people with MCAS are nuanced. Surgery-induced mast cell activation may temporarily worsen MCAS symptoms. Improved pain and quality of life without worsening MCAS-related symptoms have also been reported.

These different possibilities make an individualized assessment essential. The decision should account for endometriosis severity, MCAS severity, and the likely drivers of each symptom. Removing endometriosis lesions should not be presented as a treatment that necessarily resolves MCAS.

Perioperative planning

Planning should include consideration of preoperative mast-cell stabilizing medications and close monitoring around the time of surgery. The surgical, anesthesia, and MCAS clinicians should coordinate the plan around disease severity, known triggers, and the individual’s symptom drivers.

Questions for your surgical and MCAS clinicians include:

• Which symptoms are most likely to improve with excision, and which may need continued MCAS-directed treatment?
• How do my MCAS severity and known triggers affect the surgical and anesthesia plan?
• What mast-cell stabilizing medications should be considered before surgery, and what monitoring is planned during and immediately afterward?

Severe gastrointestinal involvement may need nutritional support

A small number of people with severe MCAS and significant gastrointestinal involvement have needed total parenteral nutrition (TPN), which supplies nutrition through a vein rather than the digestive tract. Temporary TPN has allowed select individuals to regain nutritional stability and resume eating.

TPN is a last-resort option when other interventions have failed. Its substantial risks include infection, liver dysfunction, and metabolic complications.

For people with severe gastrointestinal involvement, nutritional support remains part of a broader management plan. Dietary modification, medications tailored to mast cell control, and strategies to minimize degranulation continue to matter as oral intake is restored.