The joint effect of genetic risk factors and different types of combined oral contraceptives on venous thrombosis risk

Khialani, Deeksha; Cessie, Saskia le; Lijfering, Willem M.; Cannegieter, Suzanne C.; Rosendaal, Frits R.; Vlieg, Astrid van Hylckama

doi:10.1111/bjh.16666

Cited by 16 publications

(13 citation statements)

References 33 publications

(39 reference statements)

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“…These mutations are less frequent with a prevalence below 1% but they are associated with a 10- to 50-fold risk of first VTE ( 109 ). The presence of one of the above mutations with COCs leads to a synergistic and amplificative (rather than an additive) prothrombotic effect ( 110 ). Hugon-Rodin et al.…”

Section: State-of-the-art and Perspectivesmentioning

confidence: 99%

“…investigated the joint effect of COCs and genetic mutation, e.g., FV Leiden mutation or G20210A mutation. Both research groups have calculated a synergy index (SI), reflecting the amplificative effect of the combination of a genetic mutation with COCs above the simple addition of the independent risk alone ( 110 , 111 ). Based on this, Khialani and co-workers estimated the odds ratios at 19.3 and 24.0 in carriers of FV Leiden mutation and G20210A mutation when using the pill, respectively ( 110 ).…”

Section: State-of-the-art and Perspectivesmentioning

confidence: 99%

See 1 more Smart Citation

Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk

Morimont

Haguet

Dogné³

et al. 2021

Front. Endocrinol.

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Many factors must be considered and discussed with women when initiating a contraceptive method and the risk of venous thromboembolism (VTE) is one of them. In this review, we discuss the numerous strategies that have been implemented to reduce the thrombotic risk associated with combined oral contraceptives (COCs) from their arrival on the market until today. Evidences suggesting that COCs were associated with an increased risk of VTE appeared rapidly after their marketing. Identified as the main contributor of this risk, the dosage of the estrogen, i.e., ethinylestradiol (EE), was significantly reduced. New progestins were also synthetized (e.g., desogestrel or gestodene) but their weak androgenic activity did not permit to counterbalance the effect of EE as did the initial progestins such as levonorgestrel. Numerous studies assessed the impact of estroprogestative combinations on hemostasis and demonstrated that women under COC suffered from resistance towards activated protein C (APC). Subsequently, the European Medicines Agency updated its guidelines on clinical investigation of steroid contraceptives in which they recommended to assess this biological marker. In 2009, estradiol-containing COCs were marketed and the use of this natural form of estrogen was found to exert a weaker effect on the synthesis of hepatic proteins compared to EE. In this year 2021, a novel COC based on a native estrogen, i.e., estetrol, will be introduced on the market. Associated with drospirenone, this preparation demonstrated minor effects on coagulation proteins as compared with other drospirenone-containing COCs. At the present time, the standard of care when starting a contraception, consists of identifying the presence of hereditary thrombophilia solely on the basis of familial history of VTE. This strategy has however been reported as poorly predictive of hereditary thrombophilia. One rationale and affordable perspective which has already been considered in the past could be the implementation of a baseline screening of the prothrombotic state to provide health care professionals with objective data to support the prescription of the more appropriate contraceptive method. While this strategy was judged too expensive due to limited laboratory solutions, the endogenous thrombin potential-based APC resistance assay could now represent an interesting alternative.

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Section: State-of-the-art and Perspectivesmentioning

confidence: 99%

Section: State-of-the-art and Perspectivesmentioning

confidence: 99%

Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk

Morimont

Haguet

Dogné³

et al. 2021

Front. Endocrinol.

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“…The risk of first VTE with an FVL mutation is increased 3‐fold. Multiple studies show an increase in the risk of thrombosis ranging from 15‐ to 35‐fold in women with a FVL mutation who use COCs compared to nonusers without a prothrombotic mutation 1,73,74 . The risk of VTE with COC use is also significantly increased in women with a prothrombin gene mutation and rarer thrombophilias, such as protein C and S deficiency or antithrombin deficiency.…”

Section: Thrombosis Risk Factorsmentioning

confidence: 99%

Hormonal therapies and venous thrombosis: Considerations for prevention and management

LaVasseur

Neukam

Kartika

et al. 2022

Research and Practice in Thrombosis and Haemostasis

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Background: Venous thromboses are well-established complications of hormonal therapy. Thrombosis risk is seen with both hormonal contraceptive agents and with hormone replacement therapy for menopause and gender transition. Over the past several decades, large epidemiological studies have helped better define these risks.Objectives: To review and discuss the differences in thrombosis risk of the many of hormonal preparations available as well as their interaction with patient-specific factors. Methods:We conducted a narrative review of the available literature regarding venous thrombosis and hormonal therapies including for contraception, menopausal symptoms, and gender transition.Results: Thrombosis risk with estrogen-containing compounds increases with increasing systemic dose of estrogen. While progesterone-only-containing products are not associated with thrombosis, when paired with estrogen in combined oral contraceptives, the formulation of progesterone does impact the risk. These components, along with patient-specific factors, may influence the choice of hormonal preparation. For patients who develop thrombosis on hormonal treatment, anticoagulation is protective against future thrombosis. Duration of anticoagulation is dependent on ongoing and future hormone therapy choice. Finally, the optimal management of hormone therapy for individuals diagnosed with prothrombotic illnesses such as COVID-19 remains unclear.Conclusions: When contemplating hormonal contraception or hormone replacement therapy, clinicians must consider a variety of factors including hormone type, dose, route, personal and family history of thrombosis, and other prothrombotic risk factors to make informed, personalized decisions regarding the risk of venous thrombosis.

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“…Pour estimer le risque de MVTE, il est donc nécessaire de multiplier cet effet synergique par le risque de MVTE de la COP et le risque de MVTE dû au FVL, ce qui conduit à des risques potentiellement très élevés (supérieurs à 20). Plus récemment, l'équipe de Frits Rosendaal a publié les données obtenues dans l'étude MEGA study [18]. Celles-ci confirment l'existence de ces interactions.…”

Section: Synthèseunclassified

La balance bénéfices-risques des contraceptions hormonales estroprogestatives

Plu‐Bureau

Raccah-Tebeka

2022

Med Sci (Paris)

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La contraception hormonale estroprogestative (COP) reste la stratégie contraceptive la plus utilisée, notamment en France. Si la balance bénéfices-risques est, pour la très grande majorité des femmes, très favorable, son utilisation doit être extrêmement prudente dans certaines situations cliniques et, en particulier, chez les femmes à risque vasculaire. Il est donc indispensable de renseigner l’ensemble des facteurs de risque vasculaire avant toute prescription de COP, quelle que soit sa voie d’administration. D’un point de vue carcinologique, si l’utilisation de la COP est associée à une discrète augmentation du risque de cancer du sein, les bénéfices méconnus, persistant de nombreuses années après son arrêt, vis-à-vis du risque de cancer de l’ovaire et de l’endomètre, contrebalancent largement ce risque mammaire. Enfin, la COP apporte des avantages non contraceptifs, notamment dans les situations cliniques telles que les dysménorrhées ou l’endométriose invalidante, améliorant profondément la qualité de vie des femmes. Il est donc nécessaire d’évaluer très précisément le contexte clinique de chaque femme afin d’adapter la meilleure stratégie contraceptive en minimisant les risques et pour bénéficier des avantages potentiels.

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The joint effect of genetic risk factors and different types of combined oral contraceptives on venous thrombosis risk

Cited by 16 publications

References 33 publications

Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk

Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk

Hormonal therapies and venous thrombosis: Considerations for prevention and management

La balance bénéfices-risques des contraceptions hormonales estroprogestatives

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