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Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9

BMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d6423 (Published 25 October 2011) Cite this as: BMJ 2011;343:d6423
  1. Øjvind Lidegaard, professor of obstetrics and gynaecology1,
  2. Lars Hougaard Nielsen, statistician1,
  3. Charlotte Wessel Skovlund, data manager and scientific assistant1,
  4. Finn Egil Skjeldestad, professor of clinical medicine2,
  5. Ellen Løkkegaard, senior registrar in obstetrics and gynaecology3
  1. 1Gynaecological Clinic 4232, Rigshospitalet, University of Copenhagen, Denmark
  2. 2Department of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tromsø, Norway
  3. 3Department of Obstetrics and Gynaecology, Hillerød Hospital, University of Copenhagen, Denmark
  1. Correspondence to: Ø Lidegaard Lidegaard{at}rh.regionh.dk
  • Accepted 12 September 2011

Abstract

Objective To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose.

Design National historical registry based cohort study.

Setting Four registries in Denmark.

Participants Non-pregnant Danish women aged 15-49 with no history of thrombotic disease and followed from January 2001 to December 2009.

Main outcome measures Relative and absolute risks of first time venous thromboembolism.

Results Within 8 010 290 women years of observation, 4307 first ever venous thromboembolic events were recorded and 4246 included, among which 2847 (67%) events were confirmed as certain. Compared with non-users of hormonal contraception, the relative risk of confirmed venous thromboembolism in users of oral contraceptives containing 30-40 µg ethinylestradiol with levonorgestrel was 2.9 (95% confidence interval 2.2 to 3.8), with desogestrel was 6.6 (5.6 to 7.8), with gestodene was 6.2 (5.6 to 7.0), and with drospirenone was 6.4 (5.4 to 7.5). With users of oral contraceptives with levonorgestrel as reference and after adjusting for length of use, the rate ratio of confirmed venous thromboembolism for users of oral contraceptives with desogestrel was 2.2 (1.7 to 3.0), with gestodene was 2.1 (1.6 to 2.8), and with drospirenone was 2.1 (1.6 to 2.8). The risk of confirmed venous thromboembolism was not increased with use of progestogen only pills or hormone releasing intrauterine devices. If oral contraceptives with desogestrel, gestodene, or drospirenone are anticipated to increase the risk of venous thromboembolism sixfold and those with levonorgestrel threefold, and the absolute risk of venous thromboembolism in current users of the former group is on average 10 per 10 000 women years, then 2000 women would need to shift from using oral contraceptives with desogestrel, gestodene, or drospirenone to those with levonorgestrel to prevent one event of venous thromboembolism in one year.

Conclusion After adjustment for length of use, users of oral contraceptives with desogestrel, gestodene, or drospirenone were at least at twice the risk of venous thromboembolism compared with users of oral contraceptives with levonorgestrel.

Footnotes

  • We thank Torben Bjerregaard Larsen, expert in coagulation at Aalborg University Hospital, and Niels Tønder, cardiologist at Hillerød University Hospital, for their review of the 200 charts.

  • Contributors: ØL, EL, and FES planned the study, supervised the analysis, and interpreted the results. ØL wrote the manuscript. LHN did the statistical analyses and interpreted the results. CWS prepared the data from the national registry of patients and national death registry. All authors discussed and approved the final manuscript. ØL is guarantor of the study. The sponsor had no influence on the design, performance, or interpretation of the results or on the manuscript.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that: Bayer Schering Pharma is thanked for covering the expenses of the analysis. All funding was given to Rigshospitalet, and the primary investigator received no salary for his work with this study, the EMA report or this manuscript. ØL has within the last three years received honorariums for speeches on pharmacoepidemiological issues, including fees from Bayer Pharma Denmark and Novo Nordisk, and will be an expert witness for plaintiffs in a legal US case in 2011-2; FES received compensation for his work in the steering committee of the European Medicines Agency report.

  • Ethical approval: This study was approved by the Danish Data Protection Agency (Journal No 2010-41-4778). Ethical approval is not requested for registry based studies in Denmark.

  • Data sharing: No additional data available.

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