Differential risks in men and women for first and recurrent venous thrombosis: the role of genes and environment

Men have a higher risk of first and recurrent venous thrombosis than do women. However, the pathophysiology underlying this phenomenon is as yet unknown. In this review article, we assessed the prevalence and strength of genetic and acquired risk factors for venous thrombosis for men and women separately, because it is likely that either a difference in effect or distribution of a risk factor explains the risk difference between the sexes. We also summarized the sex-specific results of previous studies on the risk of first and recurrent venous thrombosis. Few explanations for the sex difference were found. The major factor, explaining about 20% difference in population-attributable fraction, was body height. No difference in prevalence or strength for other venous thrombosis risk factors was observed, such as plaster cast immobilization, hospitalization, surgery, trauma, malignancy, hyperhomocysteinemia, factor V Leiden, prothrombin G20210A, or blood group non-O. Alternative explanations for the sex difference are hypothesized in this review, including X- or Y-linked mutations or a mutation on a gene with a sex-specific effect. Future studies should focus on the sex-specific risk of venous thrombosis to unravel the pathophysiology and thereby improve sex-specific treatment and prevention strategies. Even so, male sex can be used as a tool through which individuals at increased risk of first or recurrent venous thrombosis may be identified.