Venous thromboembolism, oral contraceptive risk

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). 

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... 

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). 

England that the Committee on Safety of Medicines had written to prescribers in 1995 stating that three unpublished studies on the safety of combined oral contraceptives in relation to venous thromboembolism had indicated about a two-fold increase in the risk of such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. 

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. 

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. 

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. 

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. 

The current consensus is that the contemporary low-dose preparations pose minimal risks in women who have no predisposing risk factors and, in fact, may provide certain beneficial health effects (e.g., protection against endometrial and ovarian cancer). Oral contraceptive pills have been associated with increased risk for myocardial infarction, stroke, and venous thromboembolism. However, studies have been published that suggest that these risks are minimal in appropriately chosen low-risk women. 

Stroke is a very uncommon event in childbearing women, occurring in approximately 11 per 100,000 women over a 1-year period of time. Therefore, even a doubling of this risk with oral contraceptive pills would have minimal effect on attributable risk. The estimated risk of myocardial infarction associated with oral contraceptive pill use in nonsmokers is 3 per million women over 1 year. The estimated risk of venous thromboembolism attributable to oral contraceptive pills is less than 3 per 10,000 women per year. However, the risk may be increased in women who smoke or have other predisposing factors to thrombosis or thromboembolism. In fact, it should be emphasized that the risk of serious cardiovascular side effects is particularly marked in women over 35 years of age who are heavy smokers (e.g., more than 15 cigarettes per day). Additionally, the literature suggests that there may be an increased risk of breast cancer associated with long-term oral contraceptive pill use in women under the age of 35. However, because the incidence of breast cancer is so relatively low in this population, the attributable risk of breast cancer from birth control pill use is small. 

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