Can Mast Cell Activation Syndrome (MCAS) be affected by hormones other than estrogen?

MCAS and Hormonal Influences Beyond Estrogen

Yes, MCAS can be affected by hormones other than estrogen, as hormonal fluctuations are recognized as triggers or potentiating factors for mast cell activation episodes. 1

Hormonal Triggers in MCAS

The AAAAI Mast Cell Disorders Committee explicitly identifies hormonal fluctuations as one of several reported triggers that can precipitate mast cell activation episodes in MCAS patients. 1 This broad categorization indicates that various hormonal changes—not limited to estrogen—can influence mast cell behavior and symptom manifestation.

Clinical Context

• Hormonal fluctuations are listed alongside other recognized triggers including hot water, alcohol, drugs, stress, exercise, infection, and physical stimuli such as pressure or friction. 1

• While the connection between specific hormonal triggers and mast cell activation is generally inconclusive except in rare monogenic disorders, clinicians should attempt to examine whether biomarker levels correlate with hormonal changes during symptomatic episodes. 1

Mechanistic Considerations

• Female sex hormones beyond estrogen, particularly progesterone, have been shown to significantly influence mast cell behavior, though the specific mechanisms in MCAS remain under investigation. 2

• The influence of hormones on mast cells likely occurs through multiple pathways, as mast cells express various G protein-coupled receptors that could potentially respond to hormonal signals. 1

Diagnostic Approach When Hormones Are Suspected

When evaluating patients who report symptom patterns correlating with hormonal cycles:

• Document temporal relationships between hormonal changes (menstrual cycle, pregnancy, menopause, thyroid fluctuations) and MCAS symptom episodes affecting at least 2 organ systems. 1

• Measure mast cell mediators (tryptase, N-methylhistamine, 11β-PGF2α, LTE4) at baseline and during acute episodes that coincide with suspected hormonal triggers. 1, 3

• Look for the characteristic pattern of episodic rather than chronic symptoms—persistent symptoms should direct you toward alternative diagnoses. 1

Key Diagnostic Requirements

The diagnosis still requires all three standard MCAS criteria regardless of trigger:

1. Episodic symptoms affecting ≥2 organ systems (cardiovascular, dermatologic, respiratory, gastrointestinal). 1, 3

2. Documented acute increases in mast cell mediators during symptomatic episodes (tryptase increase ≥20% above baseline plus 2 ng/mL, or elevated urinary metabolites). 3

3. Clinical response to mast cell-targeted therapies (H1/H2 antihistamines, leukotriene antagonists, mast cell stabilizers). 3, 4

Clinical Pitfall to Avoid

Do not diagnose MCAS based solely on chronic symptoms that correlate with hormonal cycles without documented episodic multi-system involvement and laboratory confirmation. 5, 3 Many patients with chronic symptoms attribute them to MCAS, but prospective studies show that only 2% of patients with suspected MCAS actually meet diagnostic criteria. 6

Management Implications

• If hormonal fluctuations are identified as a consistent trigger in a patient with confirmed MCAS, consider prophylactic escalation of mast cell-targeted therapy during predictable hormonal changes (e.g., menstrual cycle). 3, 4

• Standard MCAS treatment applies regardless of trigger: nonsedating H1 antihistamines at 2-4 times standard doses, H2 antihistamines, oral cromolyn sodium for GI symptoms, and leukotriene antagonists if LTE4 is elevated. 3, 4

• Patients should carry epinephrine auto-injectors for acute episodes, as hormonal triggers can precipitate anaphylaxis just like any other MCAS trigger. 3