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Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis

BMJ 2012; 345 doi: (Published 07 August 2012) Cite this as: BMJ 2012;345:e4944
  1. S Mantha, senior staff haematologist1,
  2. R Karp, clinical fellow in medicine2,
  3. V Raghavan, clinical fellow in medicine3,
  4. N Terrin, associate professor of medicine4,
  5. K A Bauer, professor of medicine25,
  6. J I Zwicker, assistant professor of medicine2
  1. 1Division of Hematology-Oncology, Lahey Clinic, Burlington, MA, USA
  2. 2Beth Israel Deaconess Medical Center, Harvard Medical School, Divisions of Thrombosis and Hemostasis and Hematology-Oncology, 330 Brookline Ave, Boston, MA 02215, USA
  3. 3Harvard Medical School, Mt Auburn Hospital, Cambridge, MA
  4. 4Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA
  5. 5Harvard Medical School, VA Boston Healthcare System, Boston, MA
  1. Correspondence to: J I Zwicker jzwicker{at}
  • Accepted 28 June 2012


Objectives To evaluate the risk of venous thromboembolic events associated with the use of progestin-only contraception and whether that risk differs with the mode of drug delivery (oral, intrauterine, or depot injection).

Design Systematic review and meta-analysis of randomised controlled trials and observational studies.

Data sources Pubmed, Embase, Cochrane Library, and reference lists of relevant reviews.

Study selection Randomised controlled trials and case-control, cohort, and cross sectional studies with venous thromboembolic outcome for progestin-only contraception reported relative to a non-hormone comparator group.

Data extraction Data were extracted by two independent investigators, and consensus for inclusion was reached after assessment by additional investigators.

Results Among the 2022 unique references identified by all searches, eight observational studies fulfilled inclusion criteria. A total of 147 women across all studies were diagnosed with a venous thromboembolic event while taking progestin-only contraception, and the summary measure for the adjusted relative risk of a venous thromboembolic episode for users versus non-users of a progestin-only contraceptive was, based on the random effects model, 1.03 (95% CI 0.76 to 1.39). Subgroup analysis confirmed there was no association between venous thromboembolic risk and progestin-only pills (relative risk 0.90 (0.57 to 1.45)) or a progestin intrauterine device (0.61 (0.24 to 1.53)). The relative risk of a venous thromboembolic event for users of an injectable progestin versus non-users was 2.67 (1.29 to 5.53).

Conclusions Published data assessing the risk of venous thromboembolism in women prescribed progestin-only contraception are limited. In this meta-analysis of eight observational studies, the use of progestin-only contraception was not associated with an increased risk of venous thromboembolism compared with non-users of hormonal contraception. The potential association between injectable progestins and thrombosis requires further study.


  • Contributors: RK and VR performed initial literature searches and data extraction. JIZ and SM performed data extraction, statistical analysis, and coauthored the manuscript. NT provided statistical analysis and editing. KAB performed manuscript review and editing.

  • Funding: This study was funded by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (grant No UL1 RR025752). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

  • All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: support from US National Institute of Health for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Data sharing: No additional data available.

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