A reevaluation of the risk for venous thromboembolism with the use of oral contraceptives and hormone replacement therapy

Background: There are many health benefits associated with the use of oral contraceptives (OCs) and hormone replacement therapy (HRT), but these agents are also associated with potential health risks. Objective: To reevaluate the current practice of with-holding OCs or HRT in women with previous venous thromboembolism (VTE) by critically reviewing the evidence that the use of OCs or HRT is associated with an increased risk for VTE. Methods: A MEDLINE literature search was performed to identify studies investigating associations between OCs and VTE or HRT and VTE. Each study was rated according to methodologic quality (level 1, low potential for bias; level 2, moderate potential for bias; level 3, high potential for bias). Results were combined across studies of similar design to determine pooled risk ratios for VTE. The results from studies investigating third-generation OCs were reported separately. Results: For OC studies (n=22), the pooled risk ratios (95% confidence intervals) in case-control studies, retrospective cohort studies, prospective cohort studies, and randomized controlled trials were 3.0 (2.6-3.4), 4.8 (2.5-7.7), 2.4 (1.6-3.5), and 1.1 (0.4-2.9), respectively. In users of third-generation OCs, the pooled risk ratio (95% confidence interval) for VTE was 5.0 (2.5-7.5). No study was rated as level 1, 6 were rated as level 2, and 16 as level 3. Methodologic limitations in these studies would tend to exaggerate the risk for VTE with OC use. For HRT studies (n=9), the pooled risk ratios (95% confidence intervals) in case-control studies, prospective cohort studies, and randomized controlled trials were 2.4 (1.7-3.5), 1.7 (1.0-2.9), and 0.7 (0.3-1.6), respectively. No study was rated as level 1, 6 were rated as level 2, and 3 as level 3. Conclusions: First, an association between OC use and VTE is likely valid, but the reported risks are probably exaggerated. We estimate that users of non-third-generation OCs have a less than 3-fold increase in the risk for VTE compared with nonusers; the risk for VTE is possibly higher with the use of third-generation OCs. Second, an association between HRT use and VTE might exist: however, further investigation is required before definitive conclusions can be made.