Thrombophilia and hormonal therapy (oralcontraceptives and hormonal replacement therapy)

Haema 2014; 5(1):78-88

by Marianna Politou, Serena Valssami

Transfusion Service and Laboratory Haematology, Areteio University Hospital, Athens, Greece

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Venous thromboembolism (VTE) represents a serious complication associated with oral contraceptives (OCs) and hormone replacement therapy (HRT) use. The risk of VTE in OCs and HRT users is 2 to 6 fold higher leading to an absolute risk of 1-3 cases/10000women-years and 2,3/1000 women- years for OCs and HRT users respectively. Resistance to activated protein C (APC) has been suggested as a plausible biological mechanism of increasing the risk of VTE in OCs users, mainly caused by protein S and TFPI reduction. The OCs containing third generation progestins (desogestrel or gestodene) appear to have a greater risk of VTE than those with levonorgestrel. Combination OCs containing 35 μg or less of ethinyl estradiol and a second generation progestin are associated with a lower risk of VTE and hence should be preferred especially in first time OCs users. The risk of VTEs is higher in the first 6 months to 1 year of OCs use, particularly among first-time users. The risk of VTE is exponentially higher (supradditive effect) in women with hereditary thrombophilia. According to the recommendations of the World Health Organization OCs are contraindicated a) in women with any kind of thrombophilia, b) in women with a previous history of VTE) and c) in those on chronic anticoagulants for VTE. However in women with mild thrombophilia (FVLeiden FIIG20210A carriers) the risk for VTE is higher during pregnancy and postpartum period than during OCs use. Therefore, for women with mild thrombophilia, an adequate contraceptive method is necessary, combining acceptable risk of VTE and effective birth control. Current, guidelines recommend progestin only contraceptives as a safe method of birth control in women with thrombophilia. Routine thrombophilia screening prior to OCs use is not recommended. However selective screening (based on the presence of personal or family history of VTE) and in asymptomatic relatives of carriers of severe thrombophilia (deficiencies of antithrombin, protein C and S or homozygosity for factor V Leiden or the prothrombin mutation G20210A) could be a more cost-effective approach. In terms of HRT use in women carriers of severe thrombophilia (deficiency of antithrombin protein C or protein S) oral HRT is not recommended. There is insufficient evidence to suggest that HRT should be completely avoided in women with other types of thrombophilia although the data show an overall increased risk of about eight times. The presence of other risk factors for VTE should be considered and the use of transdermal HRT should be an option. Universal screening for thrombophilia in women before administering HRT is not recommended.