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J Clin Endocrinol Metab. 2015 Nov;100(11):4012-20. doi: 10.1210/jc.2015-2237.

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

Author information

Evidence-Based Practice Research Program (K.M., K.B., A.A.N., V.M.M., M.H.M.), Knowledge and Evaluation Research, Center for the Science of Health Care Delivery (K.M., A.M.A.D., K.B., A.A.N., V.M.M., M.H.M.), Division of Preventive, Occupational, and Aerospace Medicine (K.M., K.B., M.H.M.), Division of Pediatric Endocrinology (A.A.N.), Division of Endocrinology, Diabetes, Metabolism and Nutrition (B.G.C.L., V.M.M.), Library Public Services (L.J.P.), and Division of General Internal Medicine, Women's Health Clinic (S.S.F.), Mayo Clinic, Rochester, Minnesota 55905.



Menopausal hormone therapy is widely used to alleviate climacteric symptoms but may increase the risk of venous and arterial vascular events.


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.


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).


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%).


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.

[Indexed for MEDLINE]

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