Risk of venous thromboembolism and the use of dienogest- and drospirenone-containing oral contraceptives: results from a German case-control study.

Objective: The primary objective of the study was to clarify whether the use of the oral contraceptive 2 mg dienogest/30 microg ethinylestradiol (DNG/EE) is associated with a higher risk of venous thromboembolism (VTE) than the use of other combined oral low-dose contraceptives (i.e. containing < or =30 microg EE), particularly oral contraceptives containing levonorgestrel (LNG). The secondary objective was to investigate the VTE risk associated with drospirenone/ethinylestradiol (DRSP/EE) in comparison to low-dose LNG/EE.

Methods: This German community-based, case-control study recruited VTE cases from the primary care sector. Eligible cases were women aged 15-49 years with a VTE between January 2002 and February 2008. Four controls (women without a confirmed or potential VTE before the index date) were matched by age and region to each case. Medical information relevant for the assessment of VTE was abstracted from patient charts. Data on personal characteristics of the patients were collected via self-administered questionnaires. At the end of the study a blinded adjudication of the reported VTE was conducted. Conditional logistic regression techniques were used, adjusting for nine potential confounders, including personal history of VTE, family history of VTE, body mass index, duration of current combined oral contraceptive (COC) use and smoking.

Results: A total of 680 VTE cases and 2720 corresponding controls were analysed. The mean age of cases and controls was - as a result of matching - almost identical (36.1 years). A total of 35, 25, and 60 of the cases had used DNG-, DRSP- and LNG-containing low-dose COCs, respectively, at the time of the VTE diagnosis. The crude odds ratio (OR) for VTE associated with current COC use in comparison to women who had never used a COC before the index date was 1.9 (95% CI 1.5-2.5), the adjusted OR was 2.3 (95% CI 1.7-3.0). The point estimate of the crude OR of DNG/EE vs any other low-dose COCs was 0.9 (95% CI 0.6-1.3), the adjusted OR was 0.9 (95% CI 0.6-1.4). The crude ORs for DNG/EE and DRSP/EE vs low-dose LNG/EE were 1.1 (95% CI 0.7-1.8) and 1.0 (95% CI 0.6-1.6), respectively; the adjusted ORs were 1.1 (95% CI 0.7-1.9) and 1.0 (95% CI 0.6-1.8).

Conclusions: The study confirms that COC use is associated with an increased risk of VTE. The VTE ORs (adjusted and crude) that compared DNG/EE and DRSP/EE with other low-dose COCs (including LNG/EE) were close to unity and do not indicate a higher risk for users of DNG/EE or DRSP/EE.