Association of Serum Sex Hormones with Hemostatic Factors in Women On and Off Hormone Therapy: The Multiethnic Study of Atherosclerosis

J Womens Health (Larchmt). 2016 Feb;25(2):166-72. doi: 10.1089/jwh.2015.5465. Epub 2015 Dec 24.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atherosclerosis / blood
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / ethnology*
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Cross-Sectional Studies
  • Dehydroepiandrosterone / blood*
  • Estradiol / blood*
  • Estrogen Replacement Therapy*
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis
  • Gonadal Steroid Hormones / blood*
  • Hemostatics
  • Humans
  • Lipoproteins / blood*
  • Longitudinal Studies
  • Middle Aged
  • Postmenopause
  • Sex Hormone-Binding Globulin / analysis*
  • United States / epidemiology

Substances

  • Biomarkers
  • Fibrin Fibrinogen Degradation Products
  • Gonadal Steroid Hormones
  • Hemostatics
  • Lipoproteins
  • Sex Hormone-Binding Globulin
  • fibrin fragment D
  • lipoprotein-associated coagulation inhibitor
  • Dehydroepiandrosterone
  • Estradiol
  • C-Reactive Protein