The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study

Abstract

Objective To assess the thrombotic risk associated with oral contraceptive use with a focus on dose of oestrogen and type of progestogen of oral contraceptives available in the Netherlands.Design Population based case-control study.Setting Six participating anticoagulation clinics in the Netherlands (Amersfoort, Amsterdam, The Hague, Leiden, Rotterdam, and Utrecht).Participants Premenopausal women <50 years old who were not pregnant, not within four weeks postpartum, and not using a hormone excreting intrauterine device or depot contraceptive. Analysis included 1524 patients and 1760 controls.Main outcome measures First objectively diagnosed episodes of deep venous thrombosis of the leg or pulmonary embolism. Odds ratios calculated by cross-tabulation with a 95% confidence interval according to Woolf’s method; adjusted odds ratios estimated by unconditional logistic regression, standard errors derived from the model.Results Currently available oral contraceptives increased the risk of venous thrombosis fivefold compared with non-use (odds ratio 5.0, 95% CI 4.2 to 5.8). The risk clearly differed by type of progestogen and dose of oestrogen. The use of oral contraceptives containing levonorgestrel was associated with an almost fourfold increased risk of venous thrombosis (odds ratio 3.6, 2.9 to 4.6) relative to non-users, whereas the risk of venous thrombosis compared with non-use was increased 5.6-fold for gestodene (5.6, 3.7 to 8.4), 7.3-fold for desogestrel (7.3, 5.3 to 10.0), 6.8-fold for cyproterone acetate (6.8, 4.7 to 10.0), and 6.3-fold for drospirenone (6.3, 2.9 to 13.7). The risk of venous thrombosis was positively associated with oestrogen dose. We confirmed a high risk of venous thrombosis during the first months of oral contraceptive use irrespective of the type of oral contraceptives.Conclusions Currently available oral contraceptives still have a major impact on thrombosis occurrence and many women do not use the safest brands with regard to risk of venous thrombosis.

Hormonal Contraceptive Use Among Adolescent Girls in Germany in Relation to Health Behavior and Biological Cardiovascular Risk Factors

“…Consequently, the estrogen content of HCs has been gradually reduced from 150 µg to 35, and the progestin component has been modified. HCs available on the market currently are considered to have fewer adverse health effects because of this lower estrogen content and altered progestin; however, some studies with more recently introduced preparations do not support this view [9,10].…”

Assessment of Some Coagulation Parameters among Clients on Hormonal Contraceptive in a Tertiary Health Facility in Sokoto, North Western, Nigeria

“…The lowering of the estrogen dose from >50 µg to 30 µg has been shown to be associated with a significant decrease in the risk of venous thrombosis [6]. The cause of differences in the coagulation and haemostatic status between women using hormonal contraceptives from widely diverse geographical areas is not clearly understood.…”

Contracepção hormonal e sistema cardiovascular

“…The high dose of EE (≥ 50 mcg) is associated with a twofold increase in risk of VTE when compared to a low dose of this hormone (<50 mcg) 9,11,12 . Recently, it was said that formulations containing 20 mcg of EE were associated with lower risk of thrombosis (OR: 0.8; 95% CI: 0.5-1.2) when compared to preparations with 30 mcg of EE, but without any significant difference in the EE dose of contraceptives (150 mcg for 15-20 mcg).…”

“…Typically, thromboembolic events occur within the first year of use of hormonal contraceptives, especially four months after the beginning of use 3,9,11 . But after a year, the time of COC use does not alter the risk of VTE 3,9 .…”