Oral contraceptives and thrombosis: an overview of study methods and recent results

Studies of the associations between oral contraceptives and cardiovascular disease are limited by the extreme rarity of these problems among young women. There are no randomized, controlled trials, and the large, prospective cohort studies only have data regarding older oral contraceptive formulations that are now little used. Historical cohort studies that use record-linkage techniques to analyze data from computerized databases represent a new approach to assessing oral contraceptive use and thrombosis. The largest new studies, with the most sophisticated analyses, use the case-control design. A surprising result of the new studies was a difference in risk of thrombosis according to progestin type. Because these are observational rather than randomized studies, clinical factors influence the choice of oral contraceptive and may bias the study results. Controversy about the surprising results has stimulated additional analyses and critical reviews in an attempt to explain the associations.