Thrombosis risk with the use of hormonal contraception among women with thrombophilia: An updated systematic review.

Abstract

Objectives: Thrombophilia is associated with an elevated risk of thrombosis, which may be further elevated with the use of hormonal contraception. Our objective was to update a previously published systematic review on thrombosis risk with the use of hormonal contraception among women with thrombophilia.

Study design: We conducted a systematic review of five databases from database inception through December 8, 2022. We searched for articles that examined risk of venous thromboembolism (VTE) or arterial thromboembolism (ATE) in women with thrombophilia using hormonal contraception compared with women using nonhormonal or no contraception. We assessed the risk of bias for each study and certainty of evidence for all outcomes.

Results: Eighteen articles met inclusion criteria; four had moderate risk of bias and 14 had high risk of bias. Odds of VTE in women with factor V Leiden (FVL) mutation or prothrombin (PT) gene mutation were elevated in combined oral contraception (COC) users vs nonusers. Odds of VTE were elevated in COC users with FVL mutation, PT gene mutation, both FVL and PT mutations, antithrombin deficiency, or protein C deficiency compared with nonusers without the mutation. Odds of stroke were elevated in COC users with FVL mutation compared with nonusers without the mutation. Evidence was mixed on whether risk was elevated in women with protein S deficiency using COC compared with nonuse. One study found elevated odds of VTE in women with FVL mutation but not women with PT gene mutation using progestin-only contraception (POC), compared with nonusers without the mutation.

Conclusions: Overall, studies found elevated odds of VTE and ATE in women with thrombophilia using COC compared with nonusers without thrombophilia. The certainty of evidence for all outcomes is low. Evidence is also limited by small numbers of women and minimal evidence on the use of patch, ring, or progestin-only contraception and is insufficient to assess differential risk by all thrombophilia types.

Implications: Use of estrogen-containing hormonal contraception might further elevate the risk of thrombosis among women with thrombophilia. Further study is needed on safety of POC use in women with thrombophilia.