EFFECT OF DIFFERENT PROGESTAGENS IN LOW ESTROGEN ORAL-CONTRACEPTIVES ON VENOUS THROMBOEMBOLIC DISEASE

A multinational hospital-based case-control study of the risk of venou s thromboembolic disease associated with combined oral contraceptives (OCs) done in 1989-93 prompted a separate inquiry comparing the risk o f venous thromboembolism (VTE) associated with low oestrogen (<35 mu g ethinyloestradiol) OCs containing levonorgestrel with risks in low oe strogen preparations containing the third-generation progestagens deso gestrel or gestodene. This analysis of data from 9 countries, involved 769 cases and 1979 age matched hospital centre, 246 community control s general practice. 137 cases and 203 controls were current users of l evonorgestrel (odds ratio [OR with 95% confidence interval] 3.5 [2.6-4 .7]), with non-users as the reference; 28 controls were current users of [4.9-17.0]), and 36 cases and 28 controls were current users of ges todene (9.1 [4.9-16.7]). The ratios of these risks, compared with levo norgestrel, were 2.6 (1.4-4.8) for both products separately, Risk esti mates adjusted for body mass index (BMI) were 3.4, 7.3, and 10.2 for l evonorgestrel, desogestrel, and gestodene, respectively, compared with non-users, and 2.2 and 3.0 for desogestrel and gestodene, respectivel y, compared with levonorgestrel. 48 (68%) cases and 48 (86%) controls exposed to desogestrel or gestodene were from the UK (Oxford region). In this centre risk estimates compared with non-users, adjusted for BM I were 2.6, 5.3, and 5.7 for levonorgestrel, desogestrel, and gestoden e, respectively. Current users of low oestrogen dose combined OCs cont aining desogestrel or gestodene appear to be at higher risk of VTE tha n users of combined OCs containing levonorgestrel. The possibility tha t these unexpected results on a secondary study objective are due to c hance, bias, or residual confounding cannot be excluded entirely and t he results need to be confirmed by independent studies. They are at va riance with the apparently more favourable metabolic effects of the ne wer progestagens. Whether the new progestagens are associated with low er risk of arterial disease (stroke and myocardial infarction) must be evaluated further.