Andrea R. Resseguie, PharmD, RPh, CACP
The oral contraceptive pill has been named by the Centers for Disease Control and Prevention as one of the top 10 health advances in the past century. Combined oral contraceptives (COCs), which are combinations of ethinyl estradiol and a progestin, are highly effective as a form of birth control. It is estimated at least 10 million women in the United States and 100 million women worldwide use COCs. However, like all drugs, COCs are not free of risks. Women taking COCs have, as with any other hormonal contraception, an increased risk of venous thromboembolism (VTE). It is estimated that the risk of VTE increases 3 to 5 times in individuals using second-generation COCs and up to 6 to 8 times in those using third-generation COCs.1
The presence of an associated risk factor (eg, thrombophilia) increases this risk.2
Until 1995, the risk of VTE associated with contraception use was exclusively attributed to ethinyl estradiol; therefore, the dose of estrogen was lowered from 100 mcg to 35 to 50 mcg in the newer-generation pills. However, it is now thought that the type of progestin may also influence the risk of VTE. This was deduced because the use of third-generation COCs (containing desogestrel, drospirenone, or gestodene) was reported to result in a higher risk of VTE than the use of second-generation COCs (containing levonorgestrel).3-5
Although most patients are willing to accept some level of risk with contraception in return for the benefit of avoiding unplanned pregnancy, it is important to consider VTE risk when initiating contraception. Not only should the risk of the particular contraception method be evaluated, but also the individual’s risk of VTE.
Patients with contributory factors such as obesity, smoking, hypertension, diabetes, high cholesterol, poor nutrition, and stress already have an increased risk of VTE. However, these risk factors can be modified through various methods, including counseling, exercise, medication, and weight loss. Other factors that increase a patient’s risk of VTE include advancing age, cancer, prior VTE, venous insufficiency, pregnancy, trauma, frailty, immobility, and thrombophilia.6
World Health Organization Recommendations
For patients with cardiovascular disease considering starting contraception, the World Health Organization has specifically made recommendations regarding deep vein thrombosis (DVT)/pulmonary embolism (PE). COCs, combined injectable contraceptives, and combined patch/vaginal ring contraceptives should all be avoided in those with a history of DVT/PE, acute DVT/PE, DVT/PE while receiving established anticoagulant therapy, major surgery with prolonged immobilization, or known thrombophilia (eg, factor V Leiden; prothrombin mutation; protein S, protein C, antithrombin deficiencies). Acceptable forms of contraception for these patients include a copper intrauterine device (IUD), a progestin-only pill, a progestin-only levonorgestrel-releasing IUD, progestin-only implants containing levonorgestrel/etonogestrel, and progestin-only injections using depot medroxyprogesterone acetate/norethisterone enanthate.7
It is important for clinicians to understand that in patients at risk of acute DVT/PE, the potential harm outweighs the expected benefit from using any type of hormonal contraceptive. Other methods of preventing pregnancy include barrier methods such as condoms (male and female), diaphragms, and cervical caps.
Patients with other cardiovascular conditions also require special attention when selecting contraception. These conditions include multiple risk factors for cardiovascular disease, hypertension, history of high blood pressure during pregnancy, superficial venous thrombosis, ischemic heart disease, stroke, hyperlipidemia, and valvular heart disease.
To minimize a patient’s risk for VTE while using hormonal contraception, in addition to careful patient selection, clinicians should consider the possibility of thromboembolic disorder irrespective of the type of contraception used. Thrombogenic mutations are genetic, which should be considered in patients with a first-degree relative who has had VTE. Despite this, testing for thrombophilias in women at high risk of VTE is controversial and thus hormonal contraception is generally not recommended for these women.
Dr. Resseguie is an advanced practice anticoagulation pharmacist for the Brigham & Women’s Hospital Anticoagulation Management Service in Boston, Massachusetts.
Piparva KG, Buch JG. Deep vein thrombosis in a woman taking oral combined contraceptive pills. J Pharmacol Pharmacother. 2011;2:185-186.
van Vlijmen EFW, Veeger NJGM, Middeldorp S, et al. Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception. Blood. 2011;118:2055-2061.
Effect of different progestagens in low estrogen oral contraceptives on venous thromboembolic disease: World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1995;346:1582-1588.
Jick H, Jick S, Gurewich V, Wald Myers M, Vasilakis C. Risk of idiopathic venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet. 1995;346:1589-1593.
Kemmeren JM, Algra A, Grobbee DE. Third generation oral contraceptives and risk of venous thrombosis: meta-analysis. BMJ. 2001;323:131-134.
Goldhaber SZ. Risk factors for venous thromboembolism. J Am Coll Cardiol. 2010;29:56(1)1-7.
World Health Organization. US Medical Eligibility Criteria for Contraceptive Use, 2010. MMWR. 2010;59(RR04):1-85.