Does medroxyprogesterone (MPA) increase the risk of thrombosis?

Medroxyprogesterone and Thrombosis Risk

Injectable depot medroxyprogesterone acetate (DMPA) increases the risk of thrombosis and should be avoided in patients with risk factors for thrombotic events. 1

Evidence for Thrombotic Risk

• Injectable 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 (95% CI 1.29-5.53) 1
• A case-control study demonstrated a 3.6-fold increased risk (95% CI 1.8-7.1) of VTE with DMPA compared to non-users of hormonal contraception 2
• The American College of Rheumatology specifically recommends against using DMPA in patients with antiphospholipid antibodies due to concerns about thrombogenicity 1
• The American Heart Association/American College of Cardiology guidelines state that injectable DMPA should be avoided in women with chronic coronary disease or previous stroke due to increased thrombosis risk 1

Mechanism of Thrombotic Risk

• Progestins affect multiple hemostatic pathways, with different progestin types having variable effects on thrombosis risk 3
• The specific progestin and its serum level affect thrombosis risk, with some progestins having more prothrombotic effects than others 1
• Medroxyprogesterone acetate appears to have a more unfavorable thrombotic profile compared to other progestins such as micronized progesterone 4

Comparison with Other Contraceptive Options

• Progestin-only pills and levonorgestrel IUDs do not appear to increase VTE risk, with relative risks of 0.90 (95% CI 0.57-1.45) and 0.61 (95% CI 0.24-1.53), respectively 1
• A case-control study confirmed that levonorgestrel IUDs were not associated with increased thrombosis risk (odds ratio 0.3; 95% CI 0.1-1.1) 2
• The copper IUD is a highly effective non-hormonal alternative that does not increase VTE risk 1

High-Risk Populations

• The risk of thrombosis with medroxyprogesterone is particularly concerning in patients with:
  • Positive antiphospholipid antibodies 1
  • Chronic coronary disease or previous stroke 1
  • History of previous thrombotic events 1
  • Congenital heart disease with high thrombotic risk (e.g., cyanosis, Fontan physiology) 1

Clinical Implications and Recommendations

• For women requiring contraception who have risk factors for thrombosis, the following options are preferred:
  • Copper IUD (non-hormonal) 1
  • Levonorgestrel IUD 1, 2
  • Progestin-only pills 1
• Women with chronic coronary disease should avoid both combined hormonal contraceptives and injectable DMPA 1
• The FDA label for medroxyprogesterone warns of increased risk of pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction when combined with estrogen 5

Important Caveats

• The absolute risk of thrombosis with DMPA alone remains relatively low in healthy women without additional risk factors 6
• Most studies on medroxyprogesterone and thrombosis have focused on its use as a contraceptive rather than for other indications 6
• The risk appears higher when medroxyprogesterone is combined with estrogen, as in some hormone replacement therapy regimens 7
• Individual patient risk factors (age, obesity, smoking, genetic thrombophilias) may significantly modify the thrombotic risk associated with medroxyprogesterone 7