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Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study

BMJ 1996; 312 doi: (Published 13 January 1996) Cite this as: BMJ 1996;312:83
  1. Walter O Spitzer, Strathcona professor of preventive medicinea,
  2. Michael A Lewis, assistant professora,
  3. Lothar A J Heinemann, directorb,
  4. Margaret Thorogood Kenneth D MacRae on behalf of Transnational Research Group on Oral Contraceptives and the Health of Young Women, senior lecturerc
  1. a Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada
  2. b Centre for Epidemiology and Health Research, Zepernick/Berlin, Germany
  3. c London School of Hygiene and Tropical Medicine, London
  1. Charing Cross and Westminster Medical School, London Kenneth D MacRae, reader in medical statistics. The full list of members of the group is given at the end of the article. Correspondence to: Professor W O Spitzer, Potsdam Institute of Pharmacoepidemiology and Technology Assessment (PIPTA), Otto Erich Str 7, 14482 Potsdam, Germany.
  • Accepted 13 December 1995


Objective: To test whether use of combined oral contraceptives containing third generation progestogens is associated with altered risk of venous thromboembolism.

Design: Matched case-control study.

Setting: 10 centres in Germany and United Kingdom.

Subjects: Cases were 471 women aged 16-44 who had a venous thromboembolism. Controls were 1772 women (at least 3 controls per case) unaffected by venous thromboembolism who were matched with corresponding case for age and for hospital or community setting.

Main outcome measures: Odds ratios derived with stratified analyses and unconditional logistic regression to adjust for potential confounding variables.

Results: Odds ratios (95% confidence intervals) for venous thromboembolism were: for any oral contraceptives versus no use, 4.0 (3.1 to 5.3); for second generation products (low dose ethinyloestradiol, no gestodene or desogestrel) versus no use, 3.2 (2.3 to 4.3); for third generation products (low dose ethinyloestradiol, gestodene or desogestrel) versus no use, 4.8 (3.4 to 6.7); for third generation products versus second generation products, 1.5 (1.1 to 2.1); for products containing gestodene versus second generation products, 1.5 (1.0 to 2.2); and for products containing desogestrel versus second generation products, 1.5 (1.1 to 2.2). Probability of death due to venous thromboembolism for women using third generation products is about 20 per million users per year, for women using second generation products it is about 14 per million users per year, and for non-users it is five per million per year.

Conclusions: Risk of venous thromboembolism was slightly increased in users of third generation oral contraceptives compared with users of second generation products.

Key messages

  • Key messages

  • This case-control study examined risk of venous thromboembolism associated with different types of oral contraceptive

  • Overall, there was a fourfold higher relative risk of thromboembolism associated with current use of any oral contraceptive versus no current use

  • The risk of thromboembolism was 1.5 times higher for third generation contraceptives compared with second generation products

  • Our data indicate the need for clinical prudence but allow doctors and women seeking contraception to exercise informed choice


  • Funding Unconditional grant from Schering AG Berlin.

  • Conflict of interest Study was funded by Schering AG Berlin.

  • Accepted 13 December 1995
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