Oral contraceptives venous thromboembolism

Dinger J, Shapiro S. Combined oral contraceptives, venous thromboembolism, and the problem of interpreting large but incomplete datasets. J Fam Plann Reprod Health Care 2012 38(l) 2-6. 

Spannagl, M., et al., "Are Factor V Leiden Carriers Who Use Oral Contraceptives at Extreme Risk for Venous Thromboembolism " Eur. ]. Contracept. Reprod. Hlth. Care, 5, 105-112 (2000). 

Cilest contains ethinylestradiol and norgestimate whereas Yasmin contains ethinylestradiol in combination with drospirenone. Both are combined oral contraceptives available as tablets, which have to be taken once daily for 21 days. Both are contraindicated in patients with venous thromboembolic diseases. 

The cardiovascular complications of oral contraceptives include venous thrombosis and thromboembolism, arterial damage, and hypertension. 

The Medicines Commission of the UK has reviewed all currently available relevant data and has confirmed that the incidence of venous thromboembolism is about 25 per 100 000 women per year of use (21). The incidence of venous thrombembolism in users of second-generation combined oral contraceptives is about 15 per 100 000 women per year of use. This indicates a small excess risk... 

The incidence of venous thromboembolic disease in about 540 000 women born between 1941 and 1981 and taking oral contraceptives was 4.1-4.2 cases per 10 000 woman-years (22). 

Cyproterone acetate in combination with ethinylestra-diol is indicated for the treatment of women with severe acne and moderately severe hirsutism. This product has been associated with a greater risk of venous thromboembolism than oral contraceptives. However, in a rigorous case-control study the risk of venous thromboembolism with cyproterone acetate + ethinylestradiol was not significantly greater than the risk in women who took conventional oral contraceptives (25). 

Despite the variations that are found, the overall conclusion is that oral contraceptives cause an increase in coagulation factors I (fibrinogen), II, VII, IX, X, and XII, and a reduction in antithrombin III concentrations, which would be expected to predispose to venous thromboembolism, especially if not counterbalanced by an increase either in fibrinolytic activity or of other inhibitory proteins of the coagulation, such as protein C (70). 

England that the Committee on Safety of Medicines had written to prescribers in 1995 stating that three unpublished studies on the safety of combined oral contraceptives in relation to venous thromboembolism had indicated about a two-fold increase in the risk of such conditions compared with the preceding generation of products. This issue of a two-fold increase became crucial to the case. For reasons of causation, as the Judge put it, the claimants had accepted the burden of proving that the increase in risk was not less than two-fold. 

Farmer RD, Lawrenson RA. Oral contraceptives and venous thromboembolic disease the findings from database studies in the United Kingdom and Germany. Am J Obstet Gynecol 1998 179(3 Pt 2) S78-86. 

Gerstman BB, Piper JM, Tomita DK, Ferguson WJ, Stadel BV, Lundin FE. Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease. Am J Epidemiol 1991 133(l) 32-7. 

Machin SJ, Mackie IJ, Guillebaud J. Factor V Leiden mutation, venous thromboembolism and combined oral contraceptive usage. Br J Fam Planning 1995 21 13-4. 

Badaracco MA, Vessey MP. Recurrence of venous thromboembolic disease and use of oral contraceptives. BMJ 1974 1(901) 215—7. 

Herings RM, Urquhart J, Leufkens HG. Venous thromboembolism among new users of different oral contraceptives. Lancet 1999 354(9173) 127-8. 

Sartwell PE, et al. Oral contraceptives and relative risk of death from venous and pulmonary thromboembolism in the United States an epidemiologic case-control study. Am J Epidemiol 1969 90 365. 

Jick H, Kaye JA, Vasilakis-Scaramozza C, Jick SS. Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995 cohort and case-control analysis. BMJ 2000 321(7270) 1190-5. 

Lidegaard O, Edstrom B, Kreiner S. Oral contraceptives and venous thromboembolism a five-year national case-control study. Contraception 2002 65(3) 187-96. 

Helmrich SP, Rosenberg L, Kaufman DW, Strom B, Shapiro S. Venous thromboembolism in relation to oral contraceptive use. Obstet Gynecol 1987 69(l) 91-5. 

World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. Lancet 1995 346(8990) 1582-8. 

Jick H, Jick SS, Gurewich V, Myers MW, Vasilakis C. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 1995 346(8990) 1589-93. 

Spitzer WO, Lewis MA, Heinemann LA, Thorogood M, MacRae KD. Third generation oral contraceptives and risk of venous thromboembolic disorders an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women. BMJ 1996 312(7023) 83-8. 

McPherson K. Third generation oral contraception and venous thromboembolism. BMJ 19967 312(7023) 68-9. 

Burkman RT. Venous thromboembolism and oral contraceptives current status and clinical implications. Treat Endocrinol. 2002 1 143-147. 

Wu O, Robertson L, Langhorne P, et al. Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism a systematic review. The Thrombosis Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thromb Haemost. 2005 94 17-25. 

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