Oral vs Transdermal Estrogen Therapy and Vascular Events: A Systematic Review and Meta-Analysis.

BACKGROUND: Menopausal hormone therapy is widely used to alleviate climacteric symptoms but may increase the risk of venous and arterial vascular events. OBJECTIVE: The objective was to synthesize the evidence about the risk of vascular events in postmenopausal women who use oral estrogen therapy (ET) and transdermal ET. METHODS: We searched bibliographical databases through August 2013 for longitudinal comparative studies that enrolled postmenopausal women using either oral or transdermal ET and reported the outcomes of interest: venous thromboembolism (VTE), pulmonary embolism, deep venous thrombosis (DVT), myocardial infarction (MI), and stroke. Two reviewers independently selected and appraised studies. Outcomes were pooled using random effects meta-analysis and were reported as risk ratio (RR) and 95% confidence interval (CI). RESULTS: We included 15 observational studies at moderate risk of bias with follow-up of 3 to 20.25 years. When compared to transdermal ET, oral ET was associated with increased risk of a first episode of VTE (RR, 1.63; 95% CI, 1.40-1.90; I(2) = 53%), DVT (RR, 2.09; 95% CI, 1.35-3.23; I(2) = 0 %), and possibly stroke (RR, 1.24; 95% CI, 1.03-1.48; a single case-controlled study), but not MI (RR, 1.17; 95% CI, 0.80-1.71; I(2) = 74%). CONCLUSION: Observational evidence warranting low confidence suggests that compared to transdermal ET, oral ET may be associated with increased risk of VTE and DVT, but not MI.