LETTER
Epidemiology of Oral Contraceptives and Cardiovascular Disease
Jan P. Vandenbroucke, MD, PhD;
Frans M. Helmerhorst, MD, PhD; and
Frits R. Rosendaal, MD, PhD
1 November 1998 | Volume 129 Issue 9 | Page 747
TO THE EDITOR:
Chasan-Taber and Stampfer [1] present the "recency of market introduction" as a potential source of bias in evaluating the risk for venous thrombosis associated with new oral contraceptives containing desogestrel or gestodene. The argument is that women receiving these pills started using them more recently, those receiving older contraceptives had been using them for a longer time, and the risk for thrombosis is higher in the early periods of use. The straightforward solution is to compare "like with like": women who are receiving different brands for similar time periods. This analysis was done by Jick and colleagues [2], who found that in the first 6 months of use, women receiving desogestrel and gestodene contraceptives have a sixfold to ninefold greater risk for venous thrombosis relative to women receiving levonogestrel contraceptives. In several other studies, separate analyses showed that relative risk was increased rather than decreased in the first period of use [3]. The correct interpretation of these findings is that the excess risk of desogestrel and gestodene contraceptives cannot be explained by "recency of introduction bias" because the effect does not disappear upon stratification. The higher excess risk in the first period of use indicates effect modification and supports the decision of the British and German authorities to caution against first-time prescription of these pills to young women.
Chasan-Taber and Stampfer misquote our paper: In the Leiden Thrombophilia Study, we did find the highest risk in the youngest users [4], in line with the data reported above. Because of the complexity of the issue, the World Health Organization convened an international group of independent scientists in November 1997. The main conclusions of their report, one of which is that contraceptives containing desogestrel or gestodene carry a risk for thrombosis beyond that of contraceptives containing levonorgestrel, have recently become available [5].
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Author and Article Information
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Leiden University Medical Center; 2300 RC Leiden, the Netherlands
1. Chasan-Taber L, Stampfer MJ. Epidemiology of oral contraceptives and cardiovascular disease. Ann Intern Med. 1998; 128:467-77.
2. Jick II, 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; 346:1589-93.
3. Vandenbroucke JP, Helmerhorst FM, Bloemenkamp KW, Rosendaal FR. Third-generation oral contraceptive and deep venous thrombosis: from epidemiologic controversy to new insights in coagulation. Am J Obstet Gynecol. 1997; 177:887-91.
4. Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Bueller HR, Vandenbroucke JP. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet. 1995; 346:1593-6.
5. Cardiovascular disease and steroid hormone contraception. Report of a WHO Scientific Group. WHO Technical Report Series, no. 877. Geneva: World Health Organization; 1998.
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