Estrogen, progestin, and beyond: thrombotic risk and contraceptive choices

Abstract Hormonal contraceptive therapy (estrogens and/or progestogens) includes different formulations associated with varying venous thromboembolism (VTE) risks. The thrombogenicity of combined hormonal contraceptives (CHCs) is due at least in part to multiple changes in clotting factors and the vasculature and is dependent on both estrogen dose and type of progestin. Transdermal patch and vaginal ring users have similar or higher VTE risk as combined oral contraceptive users. Progestin-only agents have varying VTE risk. While depot medroxyprogesterone acetate appears to increase VTE risk, the levonorgestrel-based intrauterine system and low-dose progestin-only pills have no additional VTE risk. There are less data for the subdermal progestin-only implant. This article reviews contraceptive-related VTE risk by agent and by clinical scenario, including in patients with inherited thrombophilia, systemic lupus erythematosus with or without antiphospholipid antibodies or antiphospholipid syndrome, and sickle cell disease. Relevant clinical practice guidelines are reviewed. A multidisciplinary approach to counseling is needed for patient-focused decision-making.