Research on the relationship between venous thromboembolism and the progestagen content of combined oral contraceptives has pointed to an increase in risk associated with products containing desogestrel and gestodene. Although many biases must have been at play in these nonexperimental studies, the errors that have been suggested and examined are not of a sufficient magnitude to account for the observed results. The most plausible explanation of the available data is that combined oral contraceptives containing desogestrel and gestodene carry a very small risk of venous thromboembolism, which exceeds the even smaller risk carried by products containing levonorgestrel. The position of norgestimate is uncertain.
PIP: In October 1995, the UK Committee on the Safety of Medicines announced, in response to still unpublished studies, that third-generation oral contraceptives (OCs) carried an elevated risk of venous thromboembolism. The research motivating this announcement was subsequently published and criticized widely for its methodology. These critiques have focused on the possibility of selective prescribing of third-generation OCs to high-risk women, preferential diagnosis of venous thromboembolism in mildly symptomatic users of these OCs, and a tendency of high-risk women to shift from older to newer products. This article reviews the available data (World Health Organization Collaborative Study, General Practice Research Data Base, Leiden Thrombophilia Study, and the Transnational Study), evaluates competing explanations, and offers a summary interpretation. Overall, the review suggests that the errors identified are not of sufficient magnitude to account for the observed results. The preponderance of scientific evidence supports the proposition that desogestrel and gestodene do, in fact, carry a very small risk of venous thromboembolism that exceeds that associated with levonorgestrel.