Progestin-only contraception and thrombosis: an updated systematic review.

Objective: Evidence is limited on whether use of progestin-only contraception (POC) is associated with risk of thrombosis. Our objective was to update an earlier systematic review on POC and thrombosis risk.

Methods: We searched for articles that examined risk of venous thromboembolism (VTE) (e.g., deep venous thrombosis or pulmonary embolism) or arterial thromboembolism (ATE) (e.g., myocardial infarction or stroke) among women with thrombogenic conditions or characteristics or in the general population using POC, compared with women using non-hormonal or no contraception, published during February 1, 2016 - November 30, 2022. We also included articles from a previous systematic review with articles published through January 2016. We assessed quality for each study and certainty of evidence for all outcomes.

Results: Thirty-three articles met inclusion criteria; one was good quality, 20 were fair quality, and 12 were poor quality. Seven articles were newly identified, and 26 were included in the previous review. Risk of VTE, but not ATE, was generally elevated with depot medroxyprogesterone acetate (DMPA) use among women with certain thrombogenic conditions or characteristics (e.g., diabetes or postpartum) and women in the general population. Risks of VTE and ATE were generally not elevated with use of other POC, including levonorgestrel intrauterine devices, implants, or progestin-only pills.

Conclusions: Evidence suggests that risk of VTE, but not ATE, is increased with DMPA use compared with non-use among women with certain thrombogenic conditions and women in the general population. Evidence does not suggest increased risk of VTE or ATE with use of other POC. While several studies examined thrombosis risk with POC use and thrombogenic conditions or characteristics, data are limited for individual conditions or characteristics and no evidence was identified for most conditions. The certainty of evidence is low or very low for all outcomes. Conclusions: Use of DMPA might increase risk of VTE among women with medical conditions associated with thrombosis and among women in the general population. Evidence does not suggest an increased risk of thrombosis with other POC. Further study is needed on safety of POC use by women with thrombogenic conditions.