title: Oral vs Transdermal Estrogen Therapy and Vascular Events: A Systematic Review and Meta-Analysis.
abstract: 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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Khaled
authors.initials: K
authors.lastname: Mohammed
authors.affiliation: 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.
authors.forename: Abd Moain
authors.initials: AM
authors.lastname: Abu Dabrh
authors.affiliation: 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.
authors.forename: Khalid
authors.initials: K
authors.lastname: Benkhadra
authors.affiliation: 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.
authors.forename: Alaa
authors.initials: A
authors.lastname: Al Nofal
authors.affiliation: 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.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Carranza Leon
authors.affiliation: 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.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Prokop
authors.affiliation: 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.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
authors.affiliation: 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.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Faubion
authors.affiliation: 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.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
mesh_terms: D000284:Administration, Oral; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008593:Menopause; D064887:Observational Studies as Topic; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology; D057968:Transdermal Patch; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000209:etiology*; D020246:Venous Thrombosis / Q000453:epidemiology / Q000209:etiology*