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

ABSTRACT: Hormone therapy (HT) is associated with increased risk of both venous and arterial thrombosis, which are multifactorial in origin.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.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.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.

SUBMITTER: Williams MS

PROVIDER: S-EPMC4761837 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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

Williams Marlene S MS Cushman Mary M Ouyang Pamela P Heckbert Susan R SR Kalyani Rita Rastogi RR Vaidya Dhanajay D

Journal of women's health (2002) 20151224 2

<h4>Background</h4>Hormone therapy (HT) is associated with increased risk of both venous and arterial thrombosis, which are multifactorial in origin.<h4>Objectives</h4>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 pos ...[more]

PMID: 26700933

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Project description:Levels of circulating of sex hormones are associated with glucose metabolism and adiposity, but little is known about their association with ectopic fat. We aimed to characterize the association between circulating sex hormones and liver fat.We conducted a cross-sectional analysis by using data from the Multiethnic Study of Atherosclerosis to assess the association of the circulating levels of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) with fatty liver. Fatty liver was defined as a reduction of ?40 Hounsfield units, measured by computed tomography, in 2835 postmenopausal women and 2899 men (45-84 years old; white, black, Hispanic, or Chinese) at 6 centers in the United States.Women in the highest tertile of bioavailable testosterone were significantly more likely to have fatty liver than women in the lowest tertile (odds ratio, 1.77; 95% confidence interval, 1.07-2.92). We found an even greater difference for level of estradiol (odds ratio, 2.49; 95% confidence interval, 1.41-4.39) after adjusting for age, race/ethnicity, waist-to-hip ratio, hypertension, total and high-density lipoprotein cholesterol, smoking, insulin sensitivity, and hormone replacement therapy use. Men in the highest tertile of estradiol level were significantly more likely to have fatty liver than men in the lowest tertile (odds ratio, 2.10; 95% confidence level, 1.29-3.40). Men in the highest tertile of SHBG were less likely to have fatty liver than those in the lowest tertile (odds ratio, 0.46; 95% confidence interval, 0.27-0.77). Other associations between hormone levels and fatty liver were not statistically significant.On the basis of a cross-sectional study, postmenopausal women with high levels of bioavailable testosterone are at greater risk for fatty liver. In men, higher levels of SHBG are associated with reduced risk for fatty liver. Higher levels of estradiol are associated with fatty liver in both sexes. This pattern is consistent with the sex-specific associations of sex hormones with other cardiometabolic risk factors.

Project description:Essentials Endogenous hormone levels' influence on hemostatic factor levels is not fully characterized. We tested for associations of endogenous hormone with hemostatic factor levels in postmenopause. Estrone levels were inversely associated with the natural anticoagulant, protein S antigen. Dehydroepiandrosterone sulfate levels were inversely associated with thrombin generation.SummaryBackground Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 μg mL-1 higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nm×min lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin.

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

Publications

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

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