ReviewProgestin-only contraception and thromboembolism: A systematic review☆
Introduction
The association between combined hormonal contraceptives and thrombosis is well established. Combined hormonal contraceptives, containing estrogen and progestin, are associated with a 2- to 3-fold increased risk of venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism (PE), compared with nonuse [1], [2]. Combined hormonal contraceptives are also associated with a 2-fold increased risk of arterial thromboembolism (ATE), including stroke and acute myocardial infarction (AMI), compared with nonuse [2], [3]. Although these events are overall rare among women of reproductive age [VTE 5–10/10,000 women years (WY), stroke 21/100,000 WY and AMI 10/100,000 WY], they can have devastating complications associated with significant morbidity [2], [3]. Development of thrombosis is most likely due to estrogen effects on the coagulation system [4]. Historically, progestin-only contraceptives (POCs) were not thought to be linked with thrombosis. However, evidence has demonstrated that combined oral contraceptives with the same estrogen dose but different progestins are associated with differential VTE risk, suggesting that the progestin component may play a role in thrombosis development [1]. In addition, few recent studies have found an elevated risk of VTE with use of POCs, specifically with use of depot medroxyprogesterone acetate (DMPA) that delivers a relatively higher dose and potency of progestin [5], [6].
The US Medical Eligibility Criteria for Contraceptive Use, 2010 (US MEC) provides guidance for safety of contraceptive methods among women with certain characteristics or medical conditions and includes guidance for many conditions associated with increased risk of thrombosis such as postpartum, history of thrombosis, thrombogenic mutations, systemic lupus erythematosus, diabetes, hypertension and others [7]. This systematic review was conducted to identify evidence on thrombosis risk associated with POC use among women with medical conditions that increase their baseline risk for thrombosis, as well as among women in the general population. This review was conducted as part of the process of updating the US MEC.
Section snippets
Materials and methods
We conducted this systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [8].
Results
The search identified 1035 articles, of which 21 met inclusion criteria (Fig. 1) [3], [5], [6], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27]. Most excluded articles addressed combined hormonal contraceptives only, did not have a comparison group of nonusers, were review articles or otherwise did not address the question of interest. Five additional articles were identified from reference lists of included articles or relevant reviews
Discussion
Evidence identified by this systematic review generally found that any risk of venous or arterial thrombosis among women with certain medical conditions was not further elevated with use of POCs. Among women with hypertension, odds of stroke were higher with use of POPs compared with nonuse, but CIs overlapped. Similar results were found among smokers using POPs. One study suggested that injectable use among women who smoke increased the odds of VTE compared with smokers who did not use
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Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention.