Contraception and Thrombophilia - A statement from the German Society of Gynecological Endocrinology and Reproductive Medicine (DGGEF e. V.) and the Professional Association of the German Gynaecologists (BVF e. V.)

Journal für Reproduktionsmedizin und Endokrinologie - Journal of Reproductive Medicine and Endocrinology 2011; 8 (Sonderheft 1): 178-218

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Keywords: Antithrombin,  factor V Leiden,  family history,  hormonal contraceptives,  patient counseling,  personal history,  Protein C,  protein S,  prothrombin 20210,  risk group,  Screening,  thrombophilia,  venous thromboembolism

Venous thromboembolism (VTE) is responsible for more than half a million deaths annually in the European Union, most in older people following surgery, but some in women of reproductive age using various hormonal contraceptives. In some parts of the population inherited defects of the blood coagulation system (factor V Leiden, prothrombin G20210A, protein C, protein S and antithrombin deficiency) are responsible for an increased risk of VTE, which is also influenced by concomitant factors: e.g. long-distance travel, immobilisation, advanced age, cigarette smoking, high BMI, surgery, malignancy, fluid loss, pregnancy, oral contraceptive use and hormone replacement therapy (HRT). Laboratory testing: General screening for thrombophilia prior to the prescription of oral contraceptives (OC) is not recommended. Laboratory testing for thrombophilia should be limited to women with a positive family and/or personal history of VTE or vascular occlusion. – Factor V Leiden is by far the most common congenital thrombophilia. Heterozygous factor V Leiden (5-fold increased VTE risk) is present in 3–13%, homozygous factor V Leiden (10-fold increased VTE risk) in up to 0.2–1% of people of European origin. – Prothrombin mutation G20210A: Autosomal dominant mutation inheritance (2% of people of European origin) leads to a 3-fold increase in VTE risk is substantially increased if one or more additional risk factors are present such as factor V Leiden or protein C, S, or antithrombin deficiency. – Protein C and protein S: VTE risk increases with protein C or S deficiency (odds-ratio 3–15 and 5–11, respectively). – Antithrombin deficiency leads to a 4 to 50-fold increase in VTE risk depending on the type of deficiency. Female hormonal contraceptives containing progestogens with or without combination with a synthetic estrogens (mainly ethinylestradiol [EE]) or a natural estrogen (e.g. estradiol or its derivative estradiol valerate) affect the incidence of VTE in healthy women without known risk factors as follows (VTE cases per 10,000 woman-years): – No method-related increased risk (3–4): Non-hormonal contraceptives (e.g. tubal sterilisation, condoms, spermicides, behavioral methods, copper IUDs) – No or only slightly increased risk (3–4): Levonorgestrel IUS, progestogen-only pill, estrogen-free oral contraceptives – Moderately increased risk (3–10): Combined OCs (COCs) with < 50 µg EE containing norethisterone, norethisterone acetate, levonorgestrel, norgestimate, chlormadinone acetate, dienogest; COCs with estradiol valerate and dienogest; vaginal combined estrogen/progestogen ring, depot injectables – Moderately increased risk (6–14): COCs with < 50 µg EE containing desogestrel, gestodene, cyproterone acetate or drospirenone; combined estrogen/ progestogen contraceptive patch Detection of women at risk for VTE via family and personal history is absolutely required before any hormonal therapy (e.g. contraception, hormonal replacement). General screening for thrombophilia is not recommended. Additional individual risk factors must be considered. Each patient should be advised about early symptoms of vascular occlusion. For patients with an increased risk of VTE a risk-benefit analysis must be done regarding nonhormonal choices and non-contraceptive benefits of individual hormonal treatment (e.g. for COCs: regular menstrual cycles, less dysmenorrhoea, improvement of acne vulgaris). Shared decision-making and informed consent are strongly recommended.