Nine studies were included. There were 7 studies (n=2,712) on thrombophilia and OC: 6 case-control studies (two of which reported on the same study population) and 1 retrospective cohort study. There were 2 studies (n=400) on thrombophilia and HRT: 1 case-control study and 1 nested case-control study.
The studies were of relatively consistent methodological quality.
Studies of OC.
The overall odds of developing VTE with OC were nearly three times greater than that in women not taking OC (OR 3.10, 95% CI: 2.17, 4.42). However, there was significant heterogeneity among these studies (P=0.003).
There was a significant association of risk of VTE in women taking OC with factor V Leiden (OR 15.62, 95% CI: 8.66, 28.15) in 6 studies, antithrombin deficiency (OR 12.60, 95% CI: 1.37, 115.79) in 2 studies, protein C deficiency (OR 6.33, 95% CI: 1.68, 23.87) in 2 studies, protein S deficiency (OR 4.88, 95% CI: 1.39, 17.10) in 2 studies, and factor V Leiden and prothrombin G20210A (OR 7.85, 95% CI: 1.65, 37.41) in 2 studies. No significant heterogeneity was reported in any of the meta-analyses.
One study found a significant association of risk of VTE in women with elevated levels of factor VIIIc (OR 8.80, 95% CI 4.13, 18.75).
There was no significant association of risk of VTE in women with prothrombin G20210A alone (3 studies). However, there was significant heterogeneity between these studies (P<0.0001).
One study found no significant association of risk of VTE in women with protein C defiency and prothrombin G20210A.
There was little change in the results when the analyses were repeated using a fixed-effect model.
Analyses were also repeated by restricting inclusion to case-control studies, by removing one cohort study. A modest increase in the estimated risk of factor V Leiden and OC use was observed in addition to the now consistent results of individual studies and the significant increase in risk of VTE with prothrombin G20210A and OC.
Studies of HRT.
There was a significant association of risk of VTE in women using HRT with factor V Leiden (OR 13.16, 95% CI: 4.28, 40.47) in 2 studies.