The role of selective prescribing in the increased risk of VTE associated with third-generation oral contraceptives

In the early 1960s, it became apparent that oral contraception (OC) with oestroprogestogens increased the cardiovascular, venous thromboembolic (VTE), myocardial infarction (MI) and cerebrovascular accident (CVA) risk. The change in medical prescribing patterns, the reduction in ethinyloestradiol dosage and the use of less androgenic progestogens made prescribers confident that the risks would subsequently decrease. At the end of 1995 and early 1996, four publications called into question that optimism by showing that third-generation pills induced a two-fold increase in VTE risk compared with second-generation pills. A biological rationale was due to be announced later. Since then, re-analysis of the data has shown that the thrombotic risk factors are increased in third-generation OC users but, more importantly, that those users (unlike those using second-generation pills) are the women who have not had the opportunity of revealing a latent thrombophilia and are, therefore, at a greater risk of expressing it during third-generation OC intake. When these data are considered, the difference between second- and third-generation OC users in terms of VTE risk is completely destroyed. In addition and although the risk factors (smoking in particular) are concentrated in third-generation OC users, the MI risk is less in those users than in second-generation Dill users. This is particularly true in the presence of a risk factor such as smoking, No difference in risk has been observed for CVA in the general population between second- and third-generation OC users, but once more among smoking women the risk is lower with third-generation OC.