Risk of cerebral vein thrombosis and oral contraceptives

Abstract

A strong association between cerebral vein thrombosis and use of oral contraceptive use has been established in case-control studies in Dutch and Italian women of reproductive age.1Bruijn de SFTM Stam J Koopman MMW Vandenbroucke JP for the CVST Study GroupCase control study of risk of cerebral sinus thrombosis in oral contraceptive users who are carriers of hereditary prothrombotic conditions.BJM. 1998; 316: 589-593Crossref PubMed Google Scholar, 2Martinelli I Sacchi E Landi G Taioli E Duca F Mannucci PM High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and users of oral contraceptives.N Engl J Med. 1998; 338: 1793-1797Crossref PubMed Scopus (562) Google Scholar S de Bruijn and J P Vandenbroucke (May 9, p 1404)3Bruijn de SFTM Stam J Vandenbroucke JP for the CVST Study GroupIncreased risk of cerebral venous sinus thrombosis with third-generation oral contraceptives.Lancet. 1998; 351: 1404Summary Full Text Full Text PDF Scopus (76) Google Scholar have extended their original study by evaluating the risk conferred by third-generation oral contraceptives that contain gestodene or desogestrel. The investigators found that among patients who developed cerebral vein thrombosis, 56% of oral contraceptive users were taking third-generation products, compared with 38% in the control population, which yields a two-fold increased risk of cerebral venous thrombosis for third-generation compared with other types of oral contraceptives. We assessed the type of oral contraceptives used at the time of cerebral vein thrombosis by the women included in our original study.2Martinelli I Sacchi E Landi G Taioli E Duca F Mannucci PM High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and users of oral contraceptives.N Engl J Med. 1998; 338: 1793-1797Crossref PubMed Scopus (562) Google Scholar Our analysis was limited to patients who had had thrombosis from November, 1993, to June, 1998, since in the control-group information on the type of oral contraceptive used was obtained only during this period. 28 women with cerebral vein thrombosis and 196 controls (friends or partners of patients referred to the thrombosis centre) aged 15–50 years were assessed. 26 (93%) patients and 55 (28%) controls were using oral contraceptive at the time of thrombosis and at the visit (odds ratio 33·3 [95% CI 7·6–145·2]). The prevalence of third-generation oral contraceptives was 81% in patients (21 of 26) and 82% in controls (45 of 55), which yielded an odds ratio of 32·9 (7·2–151·0) with respect to non-users. The prevalence of first-generation or second-generation products was 19% in patients and 18% in controls (35·3 [5·4–228·0]). There are obvious differences between these findings and those of the Dutch investigators, who found a higher prevalence of third-generation pills in patients with cerebral vein thrombosis than in controls. One possible explanation for these differences is that our control group might not be representative of the Italian female population of reproductive age. To assess this possibility, we analysed the type of oral contraceptive used by women included in an Italian cohort study which has been underway since 1993, as part of the European Prospective Investigation into Cancer and Nutrition.4Riboli E Kaaks R The EPIC project: rational and study design.Int J Epidemiol. 1997; 26: s6-s14Crossref PubMed Google Scholar Information on oral contraceptive was obtained from 4024 women of reproductive age. In 1993, 80% of those who used oral contraceptives took third-generation products, and in 1997, the figure was 90%, with no substantial differences in age categories (< 40 years 75%; > 40·84%). Therefore, our control group is representative of the Italian female population, but there are clear differences in the pattern of oral contraceptive use between Italy and the Netherlands, with the market share of third-generation pills still increasing in Italy, whereas in the Netherlands it started to fall in 1994. We concluded that third-generation oral contraceptives are associated with an increased risk for cerebral vein thrombosis, but by contrast with the report of the Dutch investigators, in Italy, the magnitude of such risk is the same as that conferred by the older and less frequently prescribed types of oral contraceptives.