[A new generation of oral contraceptives and venous thromboembolic diseases: unexpected results!].

The increased cardiovascular risk of women using oral contraceptives (OCs) is well known. Newer formulations have lower doses of ethinyl estradiol and different types and doses of progestins and contraindications have been established for women at risk. Recently published data from a large case-control study carried out in European and developing countries by the World Health Organization show that women using low-dose pills containing less than 30 mcg of ethinyl estradiol have a venous thromboembolic risk 3-4 times greater than that of nonusers. Another unexpected finding was that third generation OCs with low estrogen doses and the less androgenic progestins desogestrel or gestodene entail venous thromboembolic risks 2-3 times higher than those of first or second generation pills. The study methodology was rigorous with some 1200 cases of idiopathic venous thromboembolic disease each paired with 3 controls. The relative risks of venous thromboembolic disease were only slightly modified by adjustment for known risk factors and they were similar from one country to another. A second study was based on the General Practice Research Database a network of some 400 British physicians. The risk of venous thromboembolic disease was estimated in a case-control study using a protocol similar to that of the WHO. Its results demonstrated a doubling of the relative risks associated with third generation progestins. The third study a reanalysis of data from the Leiden study confirmed the results of the other two. The three studies leave no doubt about the reality of the association. The relationship is strong and coherent from one study to another and in different countries. In absolute terms risks of venous thromboembolic disease are low and only 1-2% are fatal. Use of third generation progestins should not be suspended without more data on their effects on incidence and mortality from other disorders. But the data demonstrate clearly the need to respect known cardiovascular contraindications to combined OC use.