title: Cross-sectional association of endogenous steroid hormone, sex hormone-binding globulin, and precursor steroid levels with hemostatic factor levels in postmenopausal women.
abstract: 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.
  
  
  
  Background 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-1higher 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.
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors: L B
authors: LB
authors: Harrington
authors: Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.
authors: B T
authors: BT
authors: Marck
authors: Department of Medicine, University of Washington, Seattle, WA, USA.
authors: K L
authors: KL
authors: Wiggins
authors: Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors: B
authors: B
authors: McKnight
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Seattle, WA, USA.
authors: S R
authors: SR
authors: Heckbert
authors: School of Nursing, University of Washington, Seattle, WA, USA.
authors: N F
authors: NF
authors: Woods
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Seattle, WA, USA.|Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA, USA.
authors: A Z
authors: AZ
authors: LaCroix
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Division of Angiology and Hemostasis, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland.
authors: M
authors: M
authors: Blondon
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Seattle, WA, USA.|Department of Health Services, University of Washington, Seattle, WA, USA.
authors: B M
authors: BM
authors: Psaty
authors: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
authors: F R
authors: FR
authors: Rosendaal
authors: Geriatric Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA.|Division of Gerontology & Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.
authors: A M
authors: AM
authors: Matsumoto
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Seattle, WA, USA.|Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, WA, USA.
authors: N L
authors: NL
authors: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000735:Androstenedione / Q000097:blood; D000991:Antithrombins / Q000378:metabolism; D003430:Cross-Sectional Studies; D003687:Dehydroepiandrosterone / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D005167:Factor VII / Q000378:metabolism; D005260:Female; D006487:Hemostasis; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013256:Steroids / Q000097:blood*; D013739:Testosterone / Q000097:blood; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D000991:Antithrombins; D011486:Protein C; D017293:Protein S; D012738:Sex Hormone-Binding Globulin; D013256:Steroids; D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D005167:Factor VII; D013917:Thrombin
keywords: epidemiology; hemostasis; hormones; postmenopause; women