Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Aug 7:345:e4944.
doi: 10.1136/bmj.e4944.

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

S Mantha  1 , R Karp, V Raghavan, N Terrin, K A Bauer, J I Zwicker
Affiliations
Review

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

S Mantha et al. BMJ. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

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: 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.

Figures

None
Fig 1 Flow diagram of studies included in meta-analysis
None
Fig 2 Adjusted relative risk of venous thromboembolism for users versus non-users of a progestin-only contraceptive, all subgroups combined
None
Fig 3 Unadjusted relative risk of venous thromboembolism for users versus non-users of a progestin-only contraceptive, all subgroups combined
None
Fig 4 Adjusted relative risk of venous thromboembolism for users versus non-users of a progestin-only contraceptive, injectable formulation only
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Helmerhorst FM, Bloemenkamp KW, Rosendaal FR, Vandenbroucke JP. Oral contraceptives and thrombotic disease: risk of venous thromboembolism. Thromb Haemost 1997;78:327-33. - PubMed
    1. Vessey M, Mant D, Smith A, Yeates D. Oral contraceptives and venous thromboembolism: findings in a large prospective study. BMJ 1986;292:526. - PMC - PubMed
    1. Gerstman BB, Piper JM, Tomita DK, Ferguson WJ, Stadel BV, Lundin FE. Oral contraceptive estrogen dose and the risk of deep venous thromboembolic disease. Am J Epidemiol 1991;133:32-7. - PubMed
    1. Lidegaard O, Lokkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 2009;339:1-8. - PMC - PubMed
    1. Van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Doggen CJ, Rosendaal FR. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 2009;339:b2921. - PMC - PubMed

MeSH terms