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Chapter 22 - Menopausal Hormone Therapy (MHT) and Venous Thrombosis

Published online by Cambridge University Press:  18 June 2020

Nicholas Panay
Queen Charlotte's & Chelsea Hospital, London
Paula Briggs
Liverpool Women's NHS Foundation Trust
Gabor T. Kovacs
Monash University, Victoria
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Venous thromboembolism (VTE) is a specific reproductive health risk for women. In pregnancy the relative risk of VTE is increased approximately 5-fold and in the puerperium it is increased by as much as 60-fold. Additionally, large numbers of women worldwide are exposed to an increased relative risk of VTE as a result of using combined hormonal contraception (CHC), in particular combined oral contraceptives (COCs). Even women undergoing infertility treatment may be exposed to situations of significantly increased risk of VTE [1]. Users of menopausal hormone therapy (MHT) have a two- to four-fold increased risk of VTE compared with non-users [2], comparable to the attributable risk of CHC. The risk for VTE induced by MHT is, however, higher in absolute figures because of the age factor per se, but is also dependent on the composition of the MHT used, since users of estrogen-only preparations have lower risk of VTE than women receiving combined estrogen-progestin preparations [3]. Also the dose and route of administration seems of importance, as women treated with transdermal MHT have lower risk of VTE than women receiving orally administered MHT, as consistently demonstrated in clinical studies [2]. Moreover, epidemiological and pharmacological factors may contribute to the precipitation of VTE among MHT users. The pharmacodynamics of MHT on the hemostatic system may be of particular interest [4], because MHT changes the inhibitory potential of coagulation significantly. Consequently, the choice of MHT may translate into clinical manifestations in thrombosis-prone individuals. Venous thrombosis mostly manifests in the deep veins of the leg, but may occur in other sites, such as the upper extremities, cerebral sinus, liver and portal veins or retinal veins. Major complications of VTE are a disabling postthrombotic syndrome or acute death from a pulmonary embolus (PE) occurring in 1–2 per cent of patients [5].

Managing the Menopause , pp. 223 - 233
Publisher: Cambridge University Press
Print publication year: 2020

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Chan, WS, Dixon, ME. The ‘ART’ of thromboembolism: a review of assisted reproductive technology and thromboembolic complications. Thromb Res 2008;121:713–26.CrossRefGoogle ScholarPubMed
556 Acon. Postmenopausal estrogen therapy: route of administration and risk of venous thromboembolism. Obstet Gynecol 2013;121:887–90.Google Scholar
Canonico, M, Plu-Bureau, G, Scarabin, PY. Progestogens and venous thromboembolism among postmenopausal women using hormone therapy. Maturitas 2011;70:354–60.CrossRefGoogle ScholarPubMed
Canonico, M. Hormone therapy and hemostasis among postmenopausal women: a review. Menopause 2014;21:753–62.Google ScholarPubMed
Rosendaal, FR. Venous thrombosis: a multicausal disease. Lancet 1999;353:1167–73.CrossRefGoogle ScholarPubMed
Rosendaal, FR, Reitsma, PH. Genetics of venous thrombosis. J Thromb Haemost 2009;7 Suppl 1:301–4.CrossRefGoogle Scholar
Roach, RE, Lijfering, WM, Helmerhorst, FM, et al. The risk of venous thrombosis in women over 50 years old using oral contraception or postmenopausal hormone therapy. J Thromb Haemost 2013;11:124–31.CrossRefGoogle ScholarPubMed
Anderson, FA, Jr., Wheeler, HB, Goldberg, RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991;151:933–8.CrossRefGoogle ScholarPubMed
Tsai, AW, Cushman, M, Rosamond, WD, et al. Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology. Arch Intern Med 2002;162:1182–9.CrossRefGoogle ScholarPubMed
White, RH. The epidemiology of venous thromboembolism. Circulation 2003;107 Suppl 1:14–8.CrossRefGoogle ScholarPubMed
Cushman, M, Kuller, LH, Prentice, R, et al. Estrogen plus progestin and risk of venous thrombosis. JAMA 2004;292:1573–80.CrossRefGoogle ScholarPubMed
Curb, JD, Prentice, RL, Bray, PF, et al. Venous thrombosis and conjugated equine estrogen in women without a uterus. Arch Intern Med 2006;166:772–80.CrossRefGoogle ScholarPubMed
Ageno, W, Becattini, C, Brighton, T, et al. Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation 2008;117:93102.CrossRefGoogle ScholarPubMed
Allman-Farinelli, MA. Obesity and venous thrombosis: a review. Semin Thromb Hemost 2011;37:903–7.CrossRefGoogle ScholarPubMed
Smith, NL, Blondon, M, Wiggins, KL, et al. Lower risk of cardiovascular events in postmenopausal women taking oral estradiol compared with oral conjugated equine estrogens. JAMA 2014;174:2531.Google ScholarPubMed
Skouby, SO, Jespersen, J. Progestins in HRT: sufferance or desire? Maturitas 2009;62:371–5.CrossRefGoogle ScholarPubMed
Smith, NL, Heckbert, SR, Lemaitre, RN, et al. Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis. JAMA 2004;292:1581–7.CrossRefGoogle ScholarPubMed
Skouby, SO, Sidelmann, JJ, Nilas, L, et al. The effect of continuous combined conjugated equine estrogen plus medroxyprogesterone acetate and tibolone on cardiovascular metabolic risk factors. Climacteric 2008;11:489–97.CrossRefGoogle ScholarPubMed
Canonico, M, Oger, E, Plu-Bureau, G, et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 2007;115:840–5.CrossRefGoogle ScholarPubMed
Blondon, M, Wiggins, KL, Van Hylckama Vlieg, A, et al. Smoking, postmenopausal hormone therapy and the risk of venous thrombosis: a population-based, case-control study. Br J Haematol 2013;163:418–20.CrossRefGoogle ScholarPubMed
Eisenberger, A, Westhoff, C. Hormone replacement therapy and venous thromboembolism. J Steroid Biochem Mol Biol 2014;142:7682.CrossRefGoogle ScholarPubMed
Sidelmann, JJ, Gram, J, Jespersen, J, et al. Fibrin clot formation and lysis: basic mechanisms. Semin Thromb Hemost 2000;26:605–18.CrossRefGoogle ScholarPubMed
Hackeng, TM, Sere, KM, Tans, G, et al. Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor. Proc Natl Acad Sci U S A. 2006;103:3106–11.CrossRefGoogle ScholarPubMed
Urano, T, Castellino, FJ, Suzuki, Y. Regulation of plasminogen activation on cell surfaces and fibrin. J Thromb Haemost 2018. doi 10.1111/jth.14157CrossRefGoogle Scholar
Bucciarelli, P, Passamonti, SM, Biguzzi, E, et al. Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism. J Thromb Haemost 2012;10:1783–91.CrossRefGoogle ScholarPubMed

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