PDF herunterladen
Thromb Haemost 2018; 118(11): 1940-1950
DOI: 10.1055/s-0038-1673613
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Prospective Study of Endogenous Hormones and Incidence of Venous Thromboembolism: The Atherosclerosis Risk in Communities Study

Nicholas S. Roetker
1   Chronic Disease Research Group, Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States
2   Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States
,
Richard F. MacLehose
2   Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States
,
Ron C. Hoogeveen
3   Section of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, The Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, Texas, United States
,
Christie M. Ballantyne
3   Section of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, The Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, Texas, United States
,
Saonli Basu
4   Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States
,
Mary Cushman
5   Division of Hematology/Oncology, Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States
,
Aaron R. Folsom
2   Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States
› Institutsangaben Funding The National Heart, Lung, and Blood Institute (NHLBI) supported LITE via R01HL059367, ARIC via contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I and ARIC laboratory work via R01HL134320-01.
Weitere Informationen

Publikationsverlauf

17. Mai 2018

23. August 2018

Publikationsdatum:
08. Oktober 2018 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Exogenous hormone treatments in women (oral contraceptives and hormone replacement therapy [HRT]) are established risk factors for venous thromboembolism (VTE), but less is known about associations between plasma levels of endogenous hormones and VTE risk. We examined the association of baseline dehydroepiandrosterone sulphate (DHEAS), testosterone and sex hormone-binding globulin (SHBG) with risk of future VTE in men and post-menopausal women in the Atherosclerosis Risk in Communities Study. Testosterone, DHEAS and SHBG were measured in plasma samples collected in 1996 to 1998. Cox proportional hazards models were used to estimate hazard ratios for incident VTE adjusting for age, race/ethnicity, body mass index, height, smoking, estimated glomerular filtration rate and C-reactive protein. All analyses were stratified by sex and by current HRT use in women. Among 3,051 non-HRT-using women, 1,414 HRT-using women and 3,925 men at risk at baseline, 184, 62 and 206 experienced incident VTE after a median follow-up of 17.6 years. Plasma hormones were not associated with incidence of VTE among men and non-HRT-using women, although lower plasma DHEAS, when modelled using quartiles or restricted cubic splines, was associated with higher risk of VTE among HRT-using women. This study does not support the existence of an important association between plasma concentrations of endogenous testosterone, DHEAS or SHBG with risk of VTE in middle-aged to older men or post-menopausal women not using HRT.

Keywords

deep vein thrombosis - pulmonary embolism - epidemiologic studies - risk factors - hormones

Supplementary Material

 

  • References

  • 1 Crous-Bou M, Harrington LB, Kabrhel C. Environmental and genetic risk factors associated with venous thromboembolism. Semin Thromb Hemost 2016; 42 (08) 808-820
    Thieme ConnectPubMedSuche in Google Scholar
  • 2 Malan NT, von Känel R, Schutte AE. , et al. Testosterone and acute stress are associated with fibrinogen and von Willebrand factor in African men: the SABPA study. Int J Cardiol 2013; 168 (05) 4638-4642
    CrossrefPubMedSuche in Google Scholar
  • 3 Agledahl I, Brodin E, Svartberg J, Hansen JB. Plasma free tissue factor pathway inhibitor (TFPI) levels and TF-induced thrombin generation ex vivo in men with low testosterone levels. Thromb Haemost 2009; 101 (03) 471-477
    Thieme ConnectPubMedSuche in Google Scholar
  • 4 Tsai AW, Cushman M, Rosamond WD. , et al. Coagulation factors, inflammation markers, and venous thromboembolism: the longitudinal investigation of thromboembolism etiology (LITE). Am J Med 2002; 113 (08) 636-642
    CrossrefPubMedSuche in Google Scholar
  • 5 Zakai NA, Lutsey PL, Folsom AR, Heckbert SR, Cushman M. Total tissue factor pathway inhibitor and venous thrombosis. The Longitudinal Investigation of Thromboembolism Etiology. Thromb Haemost 2010; 104 (02) 207-212
    Thieme ConnectPubMedSuche in Google Scholar
  • 6 Bonithon-Kopp C, Scarabin PY, Bara L, Castanier M, Jacqueson A, Roger M. Relationship between sex hormones and haemostatic factors in healthy middle-aged men. Atherosclerosis 1988; 71 (01) 71-76
    CrossrefPubMedSuche in Google Scholar
  • 7 Haring R, Baumeister SE, Völzke H. , et al. Prospective inverse associations of sex hormone concentrations in men with biomarkers of inflammation and oxidative stress. J Androl 2012; 33 (05) 944-950
    CrossrefPubMedSuche in Google Scholar
  • 8 Caron P, Bennet A, Camare R, Louvet JP, Boneu B, Sié P. Plasminogen activator inhibitor in plasma is related to testosterone in men. Metabolism 1989; 38 (10) 1010-1015
    CrossrefPubMedSuche in Google Scholar
  • 9 Yang XC, Jing TY, Resnick LM, Phillips GB. Relation of hemostatic risk factors to other risk factors for coronary heart disease and to sex hormones in men. Arterioscler Thromb 1993; 13 (04) 467-471
    CrossrefPubMedSuche in Google Scholar
  • 10 Sowers MR, Jannausch M, Randolph JF. , et al. Androgens are associated with hemostatic and inflammatory factors among women at the mid-life. J Clin Endocrinol Metab 2005; 90 (11) 6064-6071
    CrossrefPubMedSuche in Google Scholar
  • 11 Meltzer ME, Lisman T, de Groot PG. , et al. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood 2010; 116 (01) 113-121
    CrossrefPubMedSuche in Google Scholar
  • 12 Harrington LB, Marck BT, Wiggins KL. , et al. Cross-sectional association of endogenous steroid hormone, sex hormone-binding globulin, and precursor steroid levels with hemostatic factor levels in postmenopausal women. J Thromb Haemost 2017; 15 (01) 80-90
    CrossrefPubMedSuche in Google Scholar
  • 13 Folsom AR, Golden SH, Boland LL, Szklo M. Association of endogenous hormones with C-reactive protein, fibrinogen, and white blood count in post-menopausal women. Eur J Epidemiol 2005; 20 (12) 1015-1022
    CrossrefPubMedSuche in Google Scholar
  • 14 Williams MS, Cushman M, Ouyang P, Heckbert SR, Kalyani RR, Vaidya D. 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; 25 (02) 166-172
    CrossrefPubMedSuche in Google Scholar
  • 15 Labrie F, Luu-The V, Bélanger A. , et al. Is dehydroepiandrosterone a hormone?. J Endocrinol 2005; 187 (02) 169-196
    CrossrefPubMedSuche in Google Scholar
  • 16 Ohlsson C, Vandenput L, Tivesten A. DHEA and mortality: what is the nature of the association?. J Steroid Biochem Mol Biol 2015; 145: 248-253
    CrossrefPubMedSuche in Google Scholar
  • 17 Jenkins PV, Rawley O, Smith OP, O'Donnell JS. Elevated factor VIII levels and risk of venous thrombosis. Br J Haematol 2012; 157 (06) 653-663
    CrossrefPubMedSuche in Google Scholar
  • 18 Smith NL, Chen M-H, Dehghan A. , et al; Wellcome Trust Case Control Consortium. Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: the CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation 2010; 121 (12) 1382-1392
    CrossrefPubMedSuche in Google Scholar
  • 19 Folsom AR, Alonso A, George KM, Roetker NS, Tang W, Cushman M. Prospective study of plasma D-dimer and incident venous thromboembolism: the Atherosclerosis Risk in Communities (ARIC) Study. Thromb Res 2015; 136 (04) 781-785
    CrossrefPubMedSuche in Google Scholar
  • 20 Odlind V, Milsom I, Persson I, Victor A. Can changes in sex hormone binding globulin predict the risk of venous thromboembolism with combined oral contraceptive pills?. Acta Obstet Gynecol Scand 2002; 81 (06) 482-490
    PubMedSuche in Google Scholar
  • 21 Raps M, Helmerhorst F, Fleischer K. , et al. Sex hormone-binding globulin as a marker for the thrombotic risk of hormonal contraceptives. J Thromb Haemost 2012; 10 (06) 992-997
    CrossrefPubMedSuche in Google Scholar
  • 22 van Rooijen M, Silveira A, Hamsten A, Bremme K. Sex hormone--binding globulin--a surrogate marker for the prothrombotic effects of combined oral contraceptives. Am J Obstet Gynecol 2004; 190 (02) 332-337
    CrossrefPubMedSuche in Google Scholar
  • 23 Folsom AR, Cushman M, Tsai MY. , et al. A prospective study of venous thromboembolism in relation to factor V Leiden and related factors. Blood 2002; 99 (08) 2720-2725
    CrossrefPubMedSuche in Google Scholar
  • 24 Svartberg J, Braekkan SK, Laughlin GA, Hansen JB. Endogenous sex hormone levels in men are not associated with risk of venous thromboembolism: the Tromso study. Eur J Endocrinol 2009; 160 (05) 833-838
    CrossrefPubMedSuche in Google Scholar
  • 25 Holmegard HN, Nordestgaard BG, Schnohr P, Tybjaerg-Hansen A, Benn M. Endogenous sex hormones and risk of venous thromboembolism in women and men. J Thromb Haemost 2014; 12 (03) 297-305
    CrossrefPubMedSuche in Google Scholar
  • 26 Stegeman BH, Helmerhorst FM, Vos HL, Rosendaal FR, Van Hylckama Vlieg A. Sex hormone-binding globulin levels are not causally related to venous thrombosis risk in women not using hormonal contraceptives. J Thromb Haemost 2012; 10 (10) 2061-2067
    CrossrefPubMedSuche in Google Scholar
  • 27 The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. Am J Epidemiol 1989; 129 (04) 687-702
    CrossrefPubMedSuche in Google Scholar
  • 28 Cushman M, Tsai AW, White RH. , et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med 2004; 117 (01) 19-25
    CrossrefPubMedSuche in Google Scholar
  • 29 Inker LA, Schmid CH, Tighiouart H. , et al; CKD-EPI Investigators. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012; 367 (01) 20-29
    CrossrefPubMedSuche in Google Scholar
  • 30 Harrell FE. Regression Modeling Strategies: With Applications to Linear Models, Logistic and Ordinal Regression, and Survival Analysis. 2nd ed. Cham: Springer; 2015
    Suche in Google Scholar
  • 31 van Vliet HAAM, Frolich M, Christella M. , et al. Association between sex hormone-binding globulin levels and activated protein C resistance in explaining the risk of thrombosis in users of oral contraceptives containing different progestogens. Hum Reprod 2005; 20 (02) 563-568
    CrossrefPubMedSuche in Google Scholar
  • 32 Xu L, Schooling CM. Differential risks in men and women for first and recurrent venous thrombosis: the role of genes and environment: comment. J Thromb Haemost 2015; 13 (05) 884-886
    CrossrefPubMedSuche in Google Scholar
  • 33 Martinez C, Suissa S, Rietbrock S. , et al. Testosterone treatment and risk of venous thromboembolism: population based case-control study. BMJ 2016; 355: i5968
    PubMedSuche in Google Scholar
  • 34 Baillargeon J, Urban RJ, Morgentaler A. , et al. Risk of venous thromboembolism in men receiving testosterone therapy. Mayo Clin Proc 2015; 90 (08) 1038-1045
    CrossrefPubMedSuche in Google Scholar
  • 35 Sharma R, Oni OA, Chen G. , et al. Association between testosterone replacement therapy and the incidence of DVT and pulmonary embolism: a retrospective cohort study of the Veterans Administration Database. Chest 2016; 150 (03) 563-571
    CrossrefPubMedSuche in Google Scholar
  • 36 Baillargeon J, Urban RJ, Ottenbacher KJ, Pierson KS, Goodwin JS. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Intern Med 2013; 173 (15) 1465-1466
    CrossrefPubMedSuche in Google Scholar
  • 37 Brambilla DJ, O'Donnell AB, Matsumoto AM, McKinlay JB. Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clin Endocrinol (Oxf) 2007; 67 (06) 853-862
    CrossrefPubMedSuche in Google Scholar
  • 38 Valero-Politi J, Fuentes-Arderiu X. Within- and between-subject biological variations of follitropin, lutropin, testosterone, and sex-hormone-binding globulin in men. Clin Chem 1993; 39 (08) 1723-1725
    CrossrefPubMedSuche in Google Scholar
  • 39 Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 2007; 92 (02) 405-413
    CrossrefPubMedSuche in Google Scholar