Thrombosis Risk with Oral Medroxyprogesterone
Oral medroxyprogesterone acetate (MPA) is associated with an increased risk of thrombosis, particularly in patients with pre-existing risk factors for thrombotic events. 1
Mechanism and Evidence for Thrombotic Risk
- Injectable depot-medroxyprogesterone acetate (DMPA) is associated with a significantly higher risk of venous thromboembolism (VTE) compared to other progestin-only contraceptives, with a relative risk of 2.67 1
- Oral medroxyprogesterone can affect hemostatic pathways in a prothrombotic direction, though to a lesser extent than combined estrogen-progestin formulations 2
- Progestins can create a procoagulant environment with a decrease in antithrombin III and protein S levels 3
Risk Comparison with Other Contraceptive Options
- Progestin-only pills and levonorgestrel IUDs have a more favorable thrombotic risk profile compared to medroxyprogesterone, with relative risks of 0.90 and 0.61, respectively 1, 4
- Injectable DMPA shows a 3.6-fold increased risk of venous thrombosis compared with non-users of hormonal contraceptives 4
- The copper IUD is a highly effective non-hormonal alternative that does not increase VTE risk 1
High-Risk Populations
- The American College of Rheumatology specifically recommends against using DMPA in patients with antiphospholipid antibodies due to concerns about thrombogenicity 1
- Medroxyprogesterone is not recommended for patients with cyanotic congenital heart disease, prior Fontan procedure, atrial fibrillation, or pulmonary arterial hypertension due to increased thrombosis risk 3
- Women with chronic coronary disease or previous stroke should avoid injectable DMPA due to increased thrombosis risk 1
Clinical Implications and Recommendations
- For women requiring contraception who have risk factors for thrombosis, the copper IUD (non-hormonal) is a preferred option 1
- Levonorgestrel-containing IUDs or barrier methods are recommended contraceptive methods for women with cyanotic congenital heart disease and pulmonary arterial hypertension 3
- When considering medroxyprogesterone for other indications, the risk of thrombosis should be carefully weighed against potential benefits for each individual 5
Comparison with Combined Hormonal Contraceptives
- Combined estrogen-progestin contraceptives pose a higher thrombotic risk than progestin-only methods, with a 2-3 fold increased risk compared to non-users 6
- Estrogen-containing contraceptives are generally not recommended for patients at risk of thromboembolism 3
- While medroxyprogesterone carries some thrombotic risk, it induces fewer changes in the blood coagulation system than combined oral contraceptives 7
Important Considerations and Monitoring
- Patients on medroxyprogesterone should be monitored for signs of thrombosis, including leg pain/swelling, chest pain, shortness of breath, or neurological symptoms 3
- Meticulous prophylaxis for deep venous thrombosis, including early ambulation and compression stockings, is recommended for patients at high risk of thrombosis 3
- Full anticoagulation should be considered for high-risk patients requiring medroxyprogesterone therapy 3