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Background:The metabolism of estrogen contained within hormone replacement therapy (HRT) is influenced by the route of administration, and this may affect the risk of venous thromboembolism. Thrombin generation, a global coagulation assay, is a marker of hypercoagulability and is of potential use in determining the thrombotic risk associated with particular HRT administration routes. Objectives:To determine whether any effect of oral and transdermal HRT on thrombin generation is related to the plasma estrogen profile. Methods:We investigated the effects of oral, transdermal and no HRT (controls) in 52, 39 and 52 postmenopausal women, respectively, on thrombin generation, standard markers of thrombophilia, estradiol level and estrone level. Results:All parameters of thrombin generation were altered in women using oral HRT as compared with controls (P < 0.001 for all comparisons). No such differences …