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New evidence on myocardial infarction and the recent statement from the Medicines Commission giving a greater role to clinical judgment in choosing a contraceptive pill 1 call for a reassessment of the role of third generation oral contraceptives containing desogestrel or gestodene. The shift to third generation pills in the early 1990s was largely based on claims of superior cardiovascular safety. We now have evidence on which to assess these claims
A lower risk of myocardial infarction in users of third compared with users of second generation pills was found in the Transnational study, although not in the British subgroup or in women aged under 35. 2 However, the results did not take account of product specific differences in screening for hypertension before women started using the pill, which had a large effect in users of second generation pills (MA Lewis, personal communication). A similar influence had previously been found in the World Health Organisation study: in women whose blood pressure had been checked, the difference between the pill generations disappeared. 3 It seems that undiagnosed hypertension was more common in second generation users in both studies. In the largest study, the recent MICA study from the United Kingdom, no difference in risk of myocardial infarction was found between second and third generation contraceptives. 4
More contentious has been the effect of third generation contraceptives on venous thromboembolism. Four well designed studies found that third generation pills had double the risk of thrombosis of second generation pills. 5 â[euro]" 8 Subsequent studies have generally been of lower methodological quality and have had variable results. The original studies have been subjected to relentless criticism for being flawed by bias and confounding. In a $3bn world contraceptive market the stakes are high.
As third generation pills were promoted as safer, they might have been given to women at greater risk of thrombosis and so introduced bias into these...