Association of serum sex hormones with hemostatic factors in women on and off hormone therapy: The multiethnic study of atherosclerosis

Background: Hormone therapy (HT) is associated with increased risk of both venous and arterial thrombosis, which are multifactorial in origin. Objectives: Our objectives were twofold: first, we sought to examine associations between endogenous serum sex hormone levels and biomarkers of thrombosis and/or coagulation in postmenopausal hormone nonusers. Second, we separately studied the associations between serum sex hormone levels and biomarkers of thrombosis and/or coagulation in postmenopausal hormone users considering the fact that pattern of circulating hormones is different in women taking exogenous hormones. Patients/Methods: We performed a cross-sectional analysis of postmenopausal women enrolled in a large multiethnic community-based cohort study, The Multiethnic Study of Atherosclerosis. We hypothesized that higher levels of estrogen-related sex hormones would be associated with biomarkers of thrombosis, suggesting mechanisms for differences in thrombotic risk from HT. Women (n = 2878) were included if they were postmenopausal and had thrombotic biomarkers (homocysteine, fibrinogen, C-reactive protein [CRP], factor VIII, and d-dimer) and sex hormone levels (total testosterone [T], bioavailable testosterone, sex hormone binding globulin [SHBG], estradiol [E2], and dehydroepiandrosterone [DHEA]) measured. A smaller random sample of 491 women also had von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-1), and tissue factor pathway inhibitor (TFPI) levels measured. Results and Conclusions: We found that elevated levels of estradiol and SHBG in HT users were associated with elevated levels of CRP and lower levels of TFPI, both of which may be related to a prothrombotic milieu in HT users. HT nonusers had far more prothrombotic associations between elevated serum sex hormone levels and thrombotic biomarkers when compared with HT users.