Hormone therapy and venous thromboembolism

Cardiology Unit, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia.
Best Practice & Research: Clinical Endocrinology & Metabolism (Impact Factor: 4.6). 04/2003; 17(1):149-64. DOI: 10.1016/S1521-690X(02)00079-9
Source: PubMed


Convincing data from randomized trials and observational studies have demonstrated a two- to threefold increased risk of venous thromboembolism (VTE) with the use of hormone replacement therapy (HRT) in post-menopausal women. This risk is highest in the first year of use, but an increased risk persists after the first year if HRT use is ongoing. The risk of VTE is increased for oral oestrogen alone, oral oestrogen combined with progestin and probably for transdermal HRT. There is an increase in both idiopathic and non-idiopathic VTE with HRT. Early evidence suggests an interaction of HRT with thrombophilic states such as the factor V Leiden mutation, resulting in a synergistic increase in the risk of VTE. There is also an increased risk of VTE with raloxifene and tamoxifen, but the effects of low-dose HRT and tibolone on VTE risk are less clear.

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    • "For instance, oral estrogen decreases several clotting factors such as fibrinogen, tissue factor pathway inhibitor (TFPI), protein S, protein C, and antithrombin. On the other hand, HRT increases levels of the procoagulant factors: VII, X, XII, XIII, and prothrombin fragments 1+2 (F 1+2 ) as a marker of thrombin generation (Bladbjerg et al., 2003; Peverill, 2003; Guimarães et al., 2009). These facts are associated with an increase in activation of coagulation. "
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    ABSTRACT: The influence of hormone replacement therapy (HRT) on hemostasis processes depends on the type of hormone, the combination of doses, the time of taking HRT, and the route of administration (oral, transdermal, implanted). The aim of the current study was to assess some parameters of coagulation, especially tissue factor pathway inhibitor (TFPI) and tissue factor (TF) in postmenopausal women using oral or transdermal HRT. The study was conducted on 76 healthy women, including 46 women aged 44-58 years who were taking oral (26) or transdermal (20) HRT, and 30 women aged 44-54 years who did not take HRT as the control group. Plasma concentrations of TF, TFPI, thrombin-antithrombin complex (TAT), and D-dimer were performed by enzyme-linked immunosorbent assay (ELISA). Moreover, the concentration of fibrinogen and activity of protein C were measured by chromogenic and chronometric methods. We observed a significantly higher concentration of TF and a significantly lower concentration of TFPI in women taking oral and transdermal HRT in comparison with the control group. We also found a significantly lower concentration of fibrinogen in women taking oral HRT vs. the control group. Moreover, no statistically significant changes in concentrations of TAT and D-dimer, or activity of protein C were noted. In this study, the occurrence of an increased TF concentration simultaneously with a decreased concentration of TFPI in women taking HRT indicates hypercoagulability. No significant modification of TAT or D-dimer occurred, and thus there may not be increased risk of thrombosis.
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    • "The risk of thrombosis in these conditions is too high to justify MFTT. Patients taking the antiestrogen medication Tamoxifen for prevention or treatment of breast cancer should be taken off this medication before surgery because of its known thrombogenic activity [36]. For similar reasons of hypercoaguability and decreased flap perfusion and impaired wound healing, smokers should be encouraged to stop at least 1 week before surgery. "
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