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Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10

BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e2990 (Published 10 May 2012) Cite this as: BMJ 2012;344:e2990
  1. Øjvind Lidegaard, professor1,
  2. Lars Hougaard Nielsen, statistician1,
  3. Charlotte Wessel Skovlund, data manager1,
  4. Ellen Løkkegaard, senior registrar2
  1. 1Gynaecological Clinic 4232, Blegdamsvej 9, DK-2100 Copehagen Ø, Juliane Marie Centre, Rigshospitalet, University of Copenhagen, Denmark
  2. 2Department of Obstetrics and Gynaecology, Hillerød Hospital, University of Copenhagen, Denmark
  1. Correspondence to: Ø Lidegaard Lidegaard{at}rh.regionh.dk
  • Accepted 30 March 2012

Abstract

Objective To assess the risk of venous thrombosis in current users of non-oral hormonal contraception.

Design Historical national registry based cohort study.

Setting Four national registries in Denmark.

Participants All Danish non-pregnant women aged 15-49 (n=1 626 158), free of previous thrombotic disease or cancer, were followed from 2001 to 2010.

Main outcome measures Incidence rate of venous thrombosis in users of transdermal, vaginal, intrauterine, or subcutaneous hormonal contraception, relative risk of venous thrombosis compared with non-users, and rate ratios of venous thrombosis in current users of non-oral products compared with the standard reference oral contraceptive with levonorgestrel and 30-40 µg oestrogen. Diagnoses were confirmed by at least four weeks of anticoagulation therapy after the diagnosis.

Results Within 9 429 128 woman years of observation, 5287 first ever venous thrombosis events were recorded, of which 3434 were confirmed. In non-users of hormonal contraception the incidence rate of confirmed events was 2.1 per 10 000 woman years. Compared with non-users of hormonal contraception, and after adjustment for age, calendar year, and education, the relative risk of confirmed venous thrombosis in users of transdermal combined contraceptive patches was 7.9 (95% confidence interval 3.5 to 17.7) and of the vaginal ring was 6.5 (4.7 to 8.9). The corresponding incidences per 10 000 exposure years were 9.7 and 7.8 events. The relative risk was increased in women who used subcutaneous implants (1.4, 0.6 to 3.4) but not in those who used the levonorgestrel intrauterine system (0.6, 0.4 to 0.8). Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk of venous thrombosis in users of transdermal patches was 2.3 (1.0 to 5.2) and of the vaginal ring was 1.9 (1.3 to 2.7).

Conclusion Women who use transdermal patches or vaginal rings for contraception have a 7.9 and 6.5 times increased risk of confirmed venous thrombosis compared with non-users of hormonal contraception of the same age, corresponding to 9.7 and 7.8 events per 10 000 exposure years. The risk was slightly increased in women using subcutaneous implants but not in those using the levonorgestrel intrauterine system.

Footnotes

  • This study was approved by the Danish Data Protection Agency (J No 2010-41-4778).

  • Contributors: ØL planned the study, supervised the analysis, interpreted the results, and wrote the manuscript. He is guarantor of the study. EL planned the study, interpreted the results, and revised the manuscript. LHN made the statistical analyses and interpreted the results. CWS prepared all data from the national registry of patients and national death registry. All authors discussed and approved the final manuscript. ØL decided when and where to attempt publication.

  • Funding: The expenses were covered by the Gynaecological Clinic, Juliane Marie Centre, Rigshospitalet.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work. The primary investigator has within the last three years received honorariums for speeches in pharmacoepidemiological issues, including fees from Bayer Pharma Denmark, MSD Denmark, and Theramex, Monaco, and has been expert witness for plaintiff in a legal US case in 2011. EL has within the last three years participated in two congresses the expenses of which were covered by pharmaceutical companies. LHN and CWS declared no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Ethical approval is not requested for registry based studies in Denmark, and consent from participating patients is not required.

  • Data sharing: No additional data available.

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