Hormonal contraception and risk of venous thromboembolism: national follow-up studyBMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b2890 (Published 13 August 2009) Cite this as: BMJ 2009;339:b2890
- Øjvind Lidegaard, professor1,
- Ellen Løkkegaard, consultant2,
- Anne Louise Svendsen, statistician3,
- Carsten Agger, data manager4
- 1Gynaecological Clinic, Rigshospitalet, Copenhagen University, DK-2100 Copenhagen, Denmark
- 2Department of Obstetrics and Gynaecology, Hillerød Hospital, Copenhagen University
- 3Department of Biostatistics, University of Copenhagen
- 4Research Centre for Prevention and Health, Glostrup Hospital, University of Copenhagen
- Correspondence to: Ø Lidegaard
- Accepted 27 May 2009
Objective To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration.
Design National cohort study.
Setting Denmark, 1995-2005.
Participants Danish women aged 15-49 with no history of cardiovascular or malignant disease.
Main outcome measures Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period.
Results 10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use (<1 year 4.17, 95% confidence interval 3.73 to 4.66, 1-4 years 2.98, 2.73 to 3.26, and >4 years 2.76, 2.53 to 3.02; P<0.001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1.03) or with 75 μg desogestrel was 1.12 (0.36 to 3.49), and for hormone releasing intrauterine devices was 0.90 (0.64 to 1.26).
Conclusion The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis.
We thank the National Registry of Medicinal Products Statistics for providing the data on use of hormonal contraception and the National Board of Health for providing the data from the National Registry of Patients.
Contributors: ØL designed the study, planned the analysis, interpreted the results, and wrote the manuscript. He is the guarantor and responsible investigator. EL planned the study and the analysis, interpreted the results, and revised the manuscript. ALS managed data from National Registry of Patients, elaborated the logistics for the identification of the pregnant women, did the statistical analyses, interpreted the results, and revised the manuscript. CA prepared the data from National Registry of Patients and NRM, provided data from Statistics of Denmark for the analysis, and revised the manuscript.
Funding: The Gynaecological Clinic, Rigshospitalet covered the expenses for this study.
Competing interests: ØL has received grants from pharmaceutical companies for cover of research expenses and has received fees for speeches on pharmacoepidemiological topics.
Ethical approval: This study was approved by the Danish Data Protection Agency (J No 2003-41-2872). Ethical approval is not requested for registry based studies in Denmark.
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