Mast cell activation syndrome.

Estrogen stimulates mast cell degranulation and suppresses DAO, the enzyme that breaks histamine down; progesterone tends to stabilise mast cells. So the erratic estrogen and falling progesterone of perimenopause is exactly the environment where a quiet mast cell tendency becomes loud. Many women are told it is anxiety for years first.

Tryptase, plasma histamine, DAO, chromogranin A, 24-hour urine N-methylhistamine and prostaglandin D2 where appropriate, plus the drivers underneath: estradiol and progesterone, thyroid and antibodies, stool microbiome testing, mold/mycotoxin and heavy metal screening, and food sensitivity panels. We also rule out carcinoid, thyroid disease and true allergy.

A layered plan: H1 and H2 blockers, mast cell stabilisers (cromolyn, ketotifen where indicated), quercetin, luteolin, vitamin C, DAO with meals, a temporary low-histamine reset, gut repair, and careful hormone strategy — often transdermal estradiol with steady progesterone rather than fluctuating levels. Nervous-system work matters, because stress is a real degranulation trigger.

MCAS often travels with POTS and hypermobility. If you flush, faint on standing, and bruise or bend easily, we screen all three together instead of treating one and wondering why you are still unwell.