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

Endometriosis and Mast Cell Activation Syndrome: An Evolving Connection

Recent research has proposed a potential link between endometriosis and Mast Cell Activation Syndrome (MCAS), which may help explain symptom overlap in some patients.

MCAS in Context: Definition, Triggers, and Evidence

Mast Cell Activation Syndrome (MCAS) is a disorder characterized by excessive activation of mast cells—immune cells that release histamine and other inflammatory mediators. In MCAS, mast cells can become hypersensitive to triggers such as stress, environmental factors, or physical stimuli, leading to symptoms that may include flushing, itching, diarrhea, abdominal pain, and shortness of breath. Multiple studies have identified a high prevalence of mast cells in tissue samples from women with endometriosis, with reports describing elevated mast cells in up to 80% of cases. Proposed mechanisms suggest that mast cells may promote the development and persistence of endometriosis by driving inflammation, angiogenesis, and nerve growth. Endometriotic lesions themselves may release factors that activate mast cells, including VEGF, substance P, and NGF.

Integrated Care Overview

Treatment of MCAS often spans medications and lifestyle strategies, such as antihistamines to block histamine release or activity, mast cell stabilizers, leukotriene inhibitors, and approaches that include stress reduction, environmental trigger avoidance, and low-histamine diets. A reported study observed that women with both MCAS and endometriosis experienced symptom improvement when managed with a combination of hormonal therapy and MCAS-directed therapies. For individuals with endometriosis, reducing systemic inflammation and controlling lesion growth remain priorities; commonly used hormonal therapies include combined oral contraceptives, GnRH agonists, and GnRH antagonists, though some options can carry notable long-term side effects, such as bone density loss.

Detailed Options and Considerations

MCAS Treatment Modalities

• • Antihistamines to block histamine release or activity
  • Mast cell stabilizers
  • Leukotriene inhibitors
  • Stress reduction, environmental trigger avoidance, and low-histamine diets

A reported study noted symptom improvement in women with both MCAS and endometriosis when hormonal therapy was combined with MCAS-directed treatments.

Hormonal Strategies for Endometriosis

• • Combined oral contraceptives
  • GnRH agonists
  • GnRH antagonists

Note: some hormonal therapies carry notable long-term side effects, including bone density loss.

Excision Surgery and MCAS: What to Expect

Excision surgery is considered the gold-standard surgical treatment for endometriosis, but its implications for patients with MCAS are nuanced. Evidence is mixed: some research suggests that surgery-induced mast cell activation may transiently worsen MCAS symptoms, whereas other studies report improved pain and quality of life without exacerbating MCAS-related symptoms.

Perioperative Planning for Patients With MCAS

• • Preoperative mast-cell stabilizing medications
  • Close monitoring perioperatively
  • Individualized assessment of disease severity and symptom drivers

Gastrointestinal Involvement and Nutrition Support

Some patients with severe MCAS and significant gastrointestinal involvement have required total parenteral nutrition (TPN). Temporary TPN has enabled select individuals to recover nutritional stability and resume oral intake. Due to substantial risks, TPN is reserved for situations in which other interventions have failed.

Risks associated with TPN include:

• • Infection
  • Liver dysfunction
  • Metabolic complications

Core Principles of Ongoing MCAS Management

• • Dietary modification
  • Medications tailored to mast cell control
  • Strategies to minimize mast cell degranulation

Key Takeaways

Emerging evidence supports a potential connection between MCAS and endometriosis, reflected by overlapping symptoms and high mast-cell density within endometriotic lesions. Not every person with endometriosis has MCAS, and not every person with MCAS has endometriosis; however, considering MCAS in women with atypical or otherwise unexplained inflammatory symptoms may improve diagnostic accuracy and care. A personalized, multidisciplinary approach is recommended.