Venous and Arterial Thrombosis during Oral Contraceptive Use: Risks and Risk Factors Bea C. Tanis, M.D.,1 and Frits R. Rosendaal, M.D., Ph.D.1,2
ABSTRACT
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Since the introduction of oral contraceptives, their use has been associated with an increased risk of both venous and arterial thrombosis. Pulmonary embolism, myocardial infarction, and stroke are serious disorders with a considerable risk of mortality. Because worldwide over 100 million women use oral contraceptives, issues of drug safety are of great importance. The risk of venous thrombosis during low-dose oral contraceptive use is three- to sixfold increased compared with that of nonusers. The association is not only attributed to the estrogen component of the pill: the risk is twice as high for desogestrel and gestodene (third generation) containing oral contraceptives as for levonorgestrel (second generation) containing oral contraceptives. The risk of venous thrombosis is highest in the first year of use and in women with genetic or acquired risk factors for thrombosis. Both venous or arterial thrombosis are unrelated to duration of use or past use of combined oral contraceptives. The risk of myocardial infarction and stroke during low-dose oral contraceptive use is two- to fivefold increased relative to that of nonusers. The risk of arterial thrombosis induced by oral contraceptive use is more pronounced in smokers and women with hypertension, diabetes, and hypercholesterolemia. All types of thrombosis have strongly age-dependent incidences, and therefore in absolute figures the risks and effects of risk factors increase with age. The lowering of the estrogen dose in combined oral contraceptives from 50 µg to 20–30 µg in the last decade did not clearly reduce the risk of venous thrombosis, myocardial infarction, stroke, or peripheral arterial disease. For stroke and peripheral arterial disease no difference in risk was found between second and third generation oral contraceptives. For myocardial infarction study results are conflicting, and a small benefit of third- over second-generation oral contraceptives cannot be ruled out. However, this is unlikely to counterbalance the adverse effect of third generation contraceptives on venous thrombosis. KEYWORDS: Oral contraceptives, estrogens, progestagens, venous thrombosis,
arterial thrombosis, epidemiology
Educational Objectives: Upon completion of this article, the reader will be able to (1) summarize the most important determinants of venous and arterial thrombosis, and ascertain whether a putative interaction with oral contraceptive use is present, (2) comprehend the latest developments in understanding the possible mechanisms underlying an increased thrombotic risk for both venous and arterial thrombosis by oral contraceptive use, and (3) explain how second and third generation oral contraceptives differ from each other in influencing coagulation and lipid levels.
Oral Contraceptives, Pregnancy, Hormone Replacement, and Thrombosis; Editor in Chief, Jan Jacques Michiels, M.D., Ph.D.; Guest Editors, Jan Rosing, Ph.D., and F. Eric Preston, M.D.Seminars in Vascular Medicine, volume 3, number 1, 2003. Address for correspondence and reprint requests: F.R. Rosendaal, M.D., Ph.D., Department of Department of Hematology and Clinical Epidemiology, Leiden University Medical Center, Building 1, C9-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: F.R. Rosendaal@lumc.nl. 1Department of Hematology and 2Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662. 1528-9648,p;2003,03,01,069,084,ftx,en;svm00117x.
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