Gender Issues in Venous Thromboembolism

Venous thromboembolism (VTE) causes substantial morbidity and mortality. The incidence of VTE does not appear to vary significantly by gender, as evidenced by a lack of consistency in the magnitude and even direction of effect of gender in a variety of epidemiological studies of varying design. Gender does appear to affect VTE recurrence, with men having a higher rate of recurrent VTE than women. The main influence of gender upon VTE is the relationship between female gender and several well-recognized clinical risk factors for VTE: oral contraceptive pill (OCP) use, hormone replacement therapy, estrogen receptor modulator therapy, and pregnancy. The fact that women of childbearing age do not appear to have a substantially greater incidence of VTE compared to age-matched men may reflect an offsetting of these female-specific risk factors by other risk factors that are more common in men, such as trauma. Hormonal therapies are associated with a two- to three-fold increase in VTE incidence. Risk is higher with some formulations than others, during initial use, and among women who are obese, smoke, or have one of several forms of heritable thrombophilia. The pregnant state is associated with a three- to five-fold increase in VTE risk, and thromboembolism is a major cause of peripartum death. Heritable forms of thrombophilia are also important co-determinants of VTE risk in pregnancy. The mechanisms through which pregnancy and hormonal therapies increase VTE risk have not been definitively established, but hormonal effects upon levels of coagulation and anticoagulation factors likely play a role. Venous compression and venous injury also contribute to increased risk in the pregnant state.