Pregnancies and terminations after 1995 warning about third-generation oral contraceptives

On Oct 18, 1995, the Medicines Control Agency sent a warning letter based on in-press studies that reported that women who used third-generation oral contraceptives containing gestodene or desogestrel were at increased risk for venous thromboembolism compared with women using oral contraceptives containing levonorgestrel (“other” users). The warning letter raised concerns that the number of pregnancies and terminations of pregnancy (TOP) would increase. With data from the General Practice Research Database, we identified women who had received a thirdgeneration or “other” oral contraceptive prescription in the months before October, 1994, and compared their subsequent use of oral contraceptives as well as the frequency of pregnancy and TOP in the subsequent 12 months with that of women who received oral contraceptives in the months prior to October, 1995, just before the Committee on Safety of Medicines warning. The study encompassed over 31 000 users of oral contraceptives in each of the study years of which over 17 000 were users of third-generation pills. In the 1994 cohort, 77% of other users and 74% of third-generation users continued the same pill after October; 8% and 4%, respectively, switched to another oral contraceptive, and 15% and 22%, respectively, stopped taking pills. By contrast, in the 1995 cohort 79% of other users but only 14% of third-generation users continued the same pill after Oct 18, 1995. 5% of other users and 68% of third-generation users switched to an alternative oral contraceptive. The percentage of women who stopped taking oral contraceptives in the 1995 cohort was similar for both other and thirdgeneration users—16% and 18%, respectively. The 12-month frequency of pregnancies did not materially differ in the 1995 cohort compared with the 1994 cohort, nor did the frequencies differ in other users compared with third-generation users. The age-adjusted frequency of TOP in each of the 3-month periods after October 1, 1994, was similar for the two types of oral contraceptive (table). Although the frequencies of termination after Oct 1, 1995, were similar to those in the 1994 cohort, when the comparison was between types of pill users, the frequency of termination was slightly higher in the fourth quarter in thirdgeneration users (3·0 per 1000 compared with 1·8 per 1000, p<0·05, table), reflecting a low TOP frequency among other users rather than an increased frequency in third-generation users. The main findings of this study are first that, by contrast to the previous year’s experience, most third-generation users switched to another oral contraceptive shortly after the warning letter of Oct 18, 1995, but there was little change in the proportion of women who stopped using the pill. Second, the frequency of unterminated pregnancies and TOP was similar for both 12-month follow-up periods and between the different types of oral contraceptive, except possibly for the period July–September in the 1995 cohort. When we reviewed the experience of all women (oral contraceptive users and non-users) in the General Practice Research Database population, we found little differences in the frequencies of non-terminated pregnancies or pregnancy terminations between the 2-year periods. The pregnancy frequencies in the entire General Practice Research Database population less than age 50 were 30·7 and 31·4 per thousand women for the 12 months following October, 1994, and Increased risk of cerebral venous sinus thrombosis with thirdgeneration oral contraceptives