Estradiol potentiates activated FXIII

Menopausal hormone therapy may still carry a clotting risk after the liver’s first-pass processing is bypassed, and this hypothesis asks whether estradiol itself could sustain that risk in blood. The proposed target is activated factor XIII, a clot-stabilizing enzyme that cross-links proteins. In a cell-free test, purified preactivated enzyme would meet free estradiol, meaning hormone unbound to blood proteins, at concentrations measured in participants. Calcium, enzyme and soluble substrate would stay fixed. A rising substrate-turnover signal would support direct potentiation of the enzyme. A flat response across the same exposure range would reject this proposed mechanism, while leaving other explanations for excess clotting open.