Oral contraceptives and the risk of venous thromboembolism.
BACKGROUND
Oral contraceptives were introduced in the late 1950s, and their use has altered society and has led to radical changes. Combined oral contraceptives are considered the most acceptable, effective, and most easily reversible method of contraception. In the early 1960s, an association between venous thrombosis and pulmonary emboli and oral contraceptive use was identified. In response, the amount of estrogen used in these contraceptives was decreased. Later, the concept that reducing the dose of estrogen would eliminate the risk of venous thrombosis was strongly challenged.


OBJECTIVE
The available epidemiologic data and the mechanisms that underly the risk of venous thromboembolism as a side effect of oral contraceptive use will be described. Clinical implications based on both the relative and absolute risks in the general population and in women with a known tendency for venous thromboembolism will be discussed.


METHODS
A literature search of MEDLINE was conducted for the years 1995 through 2005, using search word combinations including oral contraceptive, estrogen, progestin, venous thrombosis, venous thromboembolism, pulmonary emboli, and pulmonary embolism. Relevant articles relating to the topic of oral contraceptives and the risk of venous thromboembolism were studied and summarized for inclusion in this review article.


RESULTS
Certain third-generation progestins in low-estrogen preparations were found to increase the risk of venous thrombosis and pulmonary embolism. Also, the realization that genetic factors play a role in the degree of thrombosis risk led to insights into the hemostatic changes that occur during oral contraceptive use and that predispose women to thrombosis. Known risk factors for venous thromboembolism-inherited thrombophilia, a personal history of venous thromboembolism, and obesity-pose varying degrees of concern for both women and their physicians regarding the safety of oral contraceptives.


CONCLUSIONS
In order to prevent venous thromboembolism, prudence is required when prescribing oral contraceptives to women who have an increased risk of that condition. Furthermore, having a risk factor may not be an absolute contraindication to the use of oral contraceptives, but it offers the opportunity for women to make informed decisions about their use. In the future, researchers should focus on developing effective oral contraceptives that are even safer than those that are available today.
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. s.middeldorp@amc.uva.nl
Saskia
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Middeldorp
D002318:Cardiovascular Diseases / Q000139:chemically induced; D003276:Contraceptives, Oral / Q000009:adverse effects*; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects; D018849:Controlled Clinical Trials as Topic; D005260:Female; D006801:Humans; D013923:Thromboembolism / Q000139:chemically induced* / Q000517:prevention & control; D016387:Women's Health
D003276:Contraceptives, Oral; D003277:Contraceptives, Oral, Combined; D003280:Contraceptives, Oral, Synthetic