Oral contraceptives and venous thrombosis: end of the debate?
During the more than 30-year history of oral contraceptives, clinicians have received several official warnings issued by regulating agencies on cardiovascular risks. These have affected not only gynecological practice, but also generated research activities resulting in the refined third-generation products marketed in the 1970s. The alert sent out by the UK Committee on Safety of Medicines (CSM), October 1995, on increased risk of deep venous thrombosis during use of these compounds was, therefore, very much unexpected. The statements were referring to unpublished data and, thus, indicated new and highly alarming findings. However, during the following months, although four epidemiological studies reported a 2-4 fold relative increase compared with the second-generation oral contraceptives. This relative increase means, looking at absolute risks, an excess of 1-2 cases of deep venous thrombosis per 10,000 oral contraceptive users per year. In the academic discussions following the primary publication of the four papers, the possibility of confounding factors and bias was strongly emphasized and follow-up studies together with re-analysis of the original studies have not generated evidence for the suspicion of the increased risk with third-generation oral contraceptives. In contrast, a decreasing tendency was demonstrated for more serious events such myocardial infarction. Also, the biological plausibility for increased risk of deep venous thrombosis with third-generation products is lacking, although one study has pointed to a change in the natural anticoagulatory mechanism. Obviously, the authorities have a right to react on suspicion, but the psychological and social effects of the abrupt stopping of oral contraceptive use should not be ignored, and the public understanding of scientific results is manipulated by the mass media. Following confirmed evidence from both epidemiological and biological studies, with full acknowledgement of the contraceptive and non-contraceptive benefits from oral contraceptives, an official statement should have been part of the communication strategy to prevent pill scare. A more appropriate reaction from the authorities would have been to await action until publication and scientific validation of several peer-reviewed articles and to include also absolute risks instead of relative findings.
Department of Obstetrics and Gynecology, Frederiksberg Hospital, Copenhagen, Denmark.
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D003276:Contraceptives, Oral / Q000009:adverse effects*; D005260:Female; D006801:Humans; D012307:Risk Factors; D013924:Thrombophlebitis / Q000139:chemically induced* / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology; D016387:Women's Health
D003276:Contraceptives, Oral