SEX STEROID HORMONES AND RISK OF CHD IN WOMEN

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DESCRIPTION: (Adapted from the Investigator's Abstract) Biologic studies describe diverse effects of estrogen on the cardiovascular system and observational studies indicate that exogenous hormones may decrease cardiovascular risk in postmenopausal women. However, direct data regarding whether endogenous hormone levels predict subsequent risk of coronary heart disease (CHD) are sparse and inconclusive. This application will evaluate the relationship between endogenous estrogen and androgen levels and risk of CHD among women in the Women's Health Initiative-Observational Study (WHI-OS), a prospective cohort study of 93,726 postmenopausal women age 50-79 years at study entry. Using a nested-case control design, the investigators will measure baseline sex steroid hormone levels (serum total and free estradiol, estrone sulfate, total and free testosterone, dehydroepiandrosterone sulfate) and sex hormone binding globulin to determine whether these predict subsequent risk of CHD. Case and control subjects will be selected from women who were free from cardiovascular disease and cancer at study entry and were not using hormone replacement therapy at baseline. Cases will be those women who subsequently developed a documented myocardial infarction or underwent coronary artery revascularization (N=350), while control subjects will be selected from study participants who remained free from CHD during follow-up. Controls will be matched 1:1 for age, ethnicity, smoking and follow-up time. They will also examine correlations between sex steroid hormone levels and other previously funded analyses of biomarkers, including thrombotic and inflammatory markers, lipoproteins, fasting glucose and insulin. Detailed baseline data including anthropometrics and behavioral factors will allow them to control for confounding as well as to evaluate effect modification. This study takes advantage of the unique attributes of the WHI-OS, a large scale ethnically diverse cohort of postmenopausal women with ongoing follow-up, high quality endpoint verification, and archived blood specimens, making the proposed study very efficient. The investigators state that since CHD is the leading cause of death in postmenopausal women, examining the effects of endogenous hormones in postmenopausal women is an important and promising area of inquiry.