Estrogens are prothrombotic. Recently, the Heart and Estrogen/progestin Replacement Study (HERS), renewed interest in the adverse effects of hormone replacement therapy (HRT). In HERS, HRT was no better than placebo at preventing coronary events. In post hoc analyses, treatment was associated with early harm and late benefit. In an American Heart Association funded case-control study, a potential interaction was observed between HRT and the prothrombin G20210A variant on the risk of first myocardial infarction (MI) in post-menopausal women with hypertension.