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 metaanalysis 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; I2 = 53%), DVT (RR, 2.09; 95% CI, 1.35-3.23; I2 = 0 %), andpossibly stroke (RR, 1.24;95%CI, 1.03-1.48; a single case-controlled study), but notMI(RR, 1.17; 95% CI, 0.80-1.71; I2 = 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.