 The female hormone estrogen , when used in the combined oral contraceptive pill and in <unk> hormone replacement therapy , has been associated with a two- to sixfold increased risk of venous thrombosis . The risk depends on the type of hormones used , the dose of estrogen , and the presence of other thrombophilic risk factors . Various mechanisms , such as deficiency of protein S and tissue factor pathway inhibitor , are said to be responsible . 
