New generation of progestins may raise oral contraceptive users risk of blood clots.

Three recent studies indicate that oral contraceptives (OCs) containing the progestins gestodene or desogestrel may increase the risk of venous thromboembolism in users. A World Health Organization case-control study (1143 cases 3000 controls) found that current OC users were at consistently higher risk of venous thromboembolism than nonusers. The risk was exacerbated in European OC users who had a history of pregnancy-related hypertension. Risk was closely associated with type of progestin. European users of combination OCs with the older progestins had relative risks of 3.4-4.1 whereas the new low-dose combination OC was associated with a risk 7.4 times higher than in nonusers. In developing countries these figures were 2.8-3.8 and 12.2 respectively. In a more detailed analysis of 769 hospitalized cases and 1979 hospitalized (and 246 nonhospitalized) controls it was found that OC use had a 4.1 increased risk of thromboembolism and the risk in the newer OCs was 9.4 versus 3.4 in the older formulations. In this study the risk of thromboembolism in nonusers was estimated to be 3.9/100000 woman years compared to 10.3 among levonorgestrel users and 21.3 among gestodene or desogestrel users. A computer analysis of data on healthy women in the UK under age 40 revealed that 4.3 deaths/100000 occurred in women using levonorgestrel 4.8 in those who used gestodene and 1.5 among those who used desogestrel. After controls these differences were not significant. Further analysis of cases of nonfatal venous thromboembolism indicated that women using the newer formulations had twice the risk of those using the older formulations. A Dutch study found similar results. Since this increased risk would translate into one additional death per million users per year it is difficult to make a clinical decision about the new formulations which may decrease the risk of myocardial infarction and diabetes. Further research is indicated to determine the impact of the new progestins on stroke and myocardial infarction.