title: Menopausal Hormone Therapy and Mortality: A Systematic Review and Meta-Analysis.
abstract: OBJECTIVE
  The objective was to assess the effect of menopausal hormonal therapy (MHT) on all-cause and cause-specific mortality.
  
  
  METHODS
  We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus) from inception until August 2013. We included randomized controlled trials (RCTs) of more than 6 months of duration comparing MHT with no treatment. Pairs of independent reviewers selected trials, assessed risk of bias and extracted data. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using the random-effects model.
  
  
  RESULTS
  We included 43 RCTs at moderate risk of bias. Meta-analysis showed no effect on mortality (RR 0.99 [95% CI, 0.94-1.05]), regardless of MHT type or history of preexisting heart disease. No association was found between MHT and cardiac death (RR 1.04 [95% CI 0.87-1.23]) or stroke (RR 1.49 [95% CI 0.95-2.31]). Estrogen plus progesterone use was associated with a likely increase in breast cancer mortality (RR 1.96 [95% CI 0.98-3.94]), whereas estrogen use was not. MHT use was not associated with mortality of other types of cancer. In 5 trials, MHT was likely started at a younger age: 2 RCTs with mean age less than 60 and 3 RCTs with MHT started less than 10 years after menopause. Meta-analysis of these 5 RCTs showed a reduction of mortality with MHT (RR 0.70 [95% CI 0.52-0.95]).
  
  
  CONCLUSIONS
  The current evidence suggests that MHT does not affect the risk of death from all causes, cardiac death and death from stroke or cancer. These data may be used to support clinical and policy deliberations about the role of MHT in the care of symptomatic postmenopausal women.
authors.affiliation: Evidence-Based Practice Research Program (K.B., K.M., F.A., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Knowledge and Evaluation Research Unit (K.B., K.M., F.A., V.M.M., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (K.B., K.M., A.A.N., F.A., A.M.A.D., MHM), Mayo Clinic, Rochester, Minnesota 55905; Division of Pediatric Endocrinology (A.A.N.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (B.G.C.L., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Division of General Internal Medicine (S.F.), Women's Health Clinic, Mayo Clinic, Rochester, Minnesota 55905; Facultad de Medicina (Z.H.), Universidad Autónoma de Nuevo León, Nuevo Leon, Mexico; and Mayo Clinic Libraries (L.J.P.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Khalid
authors.initials: K
authors.lastname: Benkhadra
authors.affiliation: Evidence-Based Practice Research Program (K.B., K.M., F.A., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Knowledge and Evaluation Research Unit (K.B., K.M., F.A., V.M.M., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (K.B., K.M., A.A.N., F.A., A.M.A.D., MHM), Mayo Clinic, Rochester, Minnesota 55905; Division of Pediatric Endocrinology (A.A.N.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (B.G.C.L., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Division of General Internal Medicine (S.F.), Women's Health Clinic, Mayo Clinic, Rochester, Minnesota 55905; Facultad de Medicina (Z.H.), Universidad Autónoma de Nuevo León, Nuevo Leon, Mexico; and Mayo Clinic Libraries (L.J.P.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Khaled
authors.initials: K
authors.lastname: Mohammed
authors.affiliation: Evidence-Based Practice Research Program (K.B., K.M., F.A., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Knowledge and Evaluation Research Unit (K.B., K.M., F.A., V.M.M., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (K.B., K.M., A.A.N., F.A., A.M.A.D., MHM), Mayo Clinic, Rochester, Minnesota 55905; Division of Pediatric Endocrinology (A.A.N.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (B.G.C.L., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Division of General Internal Medicine (S.F.), Women's Health Clinic, Mayo Clinic, Rochester, Minnesota 55905; Facultad de Medicina (Z.H.), Universidad Autónoma de Nuevo León, Nuevo Leon, Mexico; and Mayo Clinic Libraries (L.J.P.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Alaa
authors.initials: A
authors.lastname: Al Nofal
authors.affiliation: Evidence-Based Practice Research Program (K.B., K.M., F.A., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Knowledge and Evaluation Research Unit (K.B., K.M., F.A., V.M.M., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (K.B., K.M., A.A.N., F.A., A.M.A.D., MHM), Mayo Clinic, Rochester, Minnesota 55905; Division of Pediatric Endocrinology (A.A.N.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (B.G.C.L., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Division of General Internal Medicine (S.F.), Women's Health Clinic, Mayo Clinic, Rochester, Minnesota 55905; Facultad de Medicina (Z.H.), Universidad Autónoma de Nuevo León, Nuevo Leon, Mexico; and Mayo Clinic Libraries (L.J.P.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Carranza Leon
authors.affiliation: Evidence-Based Practice Research Program (K.B., K.M., F.A., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Knowledge and Evaluation Research Unit (K.B., K.M., F.A., V.M.M., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (K.B., K.M., A.A.N., F.A., A.M.A.D., MHM), Mayo Clinic, Rochester, Minnesota 55905; Division of Pediatric Endocrinology (A.A.N.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (B.G.C.L., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Division of General Internal Medicine (S.F.), Women's Health Clinic, Mayo Clinic, Rochester, Minnesota 55905; Facultad de Medicina (Z.H.), Universidad Autónoma de Nuevo León, Nuevo Leon, Mexico; and Mayo Clinic Libraries (L.J.P.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Fares
authors.initials: F
authors.lastname: Alahdab
authors.affiliation: Evidence-Based Practice Research Program (K.B., K.M., F.A., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Knowledge and Evaluation Research Unit (K.B., K.M., F.A., V.M.M., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (K.B., K.M., A.A.N., F.A., A.M.A.D., MHM), Mayo Clinic, Rochester, Minnesota 55905; Division of Pediatric Endocrinology (A.A.N.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (B.G.C.L., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Division of General Internal Medicine (S.F.), Women's Health Clinic, Mayo Clinic, Rochester, Minnesota 55905; Facultad de Medicina (Z.H.), Universidad Autónoma de Nuevo León, Nuevo Leon, Mexico; and Mayo Clinic Libraries (L.J.P.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Faubion
authors.affiliation: Evidence-Based Practice Research Program (K.B., K.M., F.A., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Knowledge and Evaluation Research Unit (K.B., K.M., F.A., V.M.M., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (K.B., K.M., A.A.N., F.A., A.M.A.D., MHM), Mayo Clinic, Rochester, Minnesota 55905; Division of Pediatric Endocrinology (A.A.N.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (B.G.C.L., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Division of General Internal Medicine (S.F.), Women's Health Clinic, Mayo Clinic, Rochester, Minnesota 55905; Facultad de Medicina (Z.H.), Universidad Autónoma de Nuevo León, Nuevo Leon, Mexico; and Mayo Clinic Libraries (L.J.P.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
authors.affiliation: Evidence-Based Practice Research Program (K.B., K.M., F.A., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Knowledge and Evaluation Research Unit (K.B., K.M., F.A., V.M.M., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (K.B., K.M., A.A.N., F.A., A.M.A.D., MHM), Mayo Clinic, Rochester, Minnesota 55905; Division of Pediatric Endocrinology (A.A.N.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (B.G.C.L., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Division of General Internal Medicine (S.F.), Women's Health Clinic, Mayo Clinic, Rochester, Minnesota 55905; Facultad de Medicina (Z.H.), Universidad Autónoma de Nuevo León, Nuevo Leon, Mexico; and Mayo Clinic Libraries (L.J.P.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Abd Moain
authors.initials: AM
authors.lastname: Abu Dabrh
authors.affiliation: Evidence-Based Practice Research Program (K.B., K.M., F.A., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Knowledge and Evaluation Research Unit (K.B., K.M., F.A., V.M.M., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (K.B., K.M., A.A.N., F.A., A.M.A.D., MHM), Mayo Clinic, Rochester, Minnesota 55905; Division of Pediatric Endocrinology (A.A.N.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (B.G.C.L., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Division of General Internal Medicine (S.F.), Women's Health Clinic, Mayo Clinic, Rochester, Minnesota 55905; Facultad de Medicina (Z.H.), Universidad Autónoma de Nuevo León, Nuevo Leon, Mexico; and Mayo Clinic Libraries (L.J.P.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Jorge Alberto
authors.initials: JA
authors.lastname: Zúñiga Hernández
authors.affiliation: Evidence-Based Practice Research Program (K.B., K.M., F.A., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Knowledge and Evaluation Research Unit (K.B., K.M., F.A., V.M.M., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (K.B., K.M., A.A.N., F.A., A.M.A.D., MHM), Mayo Clinic, Rochester, Minnesota 55905; Division of Pediatric Endocrinology (A.A.N.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (B.G.C.L., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Division of General Internal Medicine (S.F.), Women's Health Clinic, Mayo Clinic, Rochester, Minnesota 55905; Facultad de Medicina (Z.H.), Universidad Autónoma de Nuevo León, Nuevo Leon, Mexico; and Mayo Clinic Libraries (L.J.P.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Prokop
authors.affiliation: Evidence-Based Practice Research Program (K.B., K.M., F.A., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Knowledge and Evaluation Research Unit (K.B., K.M., F.A., V.M.M., A.M.A.D., M.H.M.), Mayo Clinic, Rochester, Minnesota 55905; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (K.B., K.M., A.A.N., F.A., A.M.A.D., MHM), Mayo Clinic, Rochester, Minnesota 55905; Division of Pediatric Endocrinology (A.A.N.), Mayo Clinic, Rochester, Minnesota 55905; Division of Endocrinology (B.G.C.L., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905; Division of General Internal Medicine (S.F.), Women's Health Clinic, Mayo Clinic, Rochester, Minnesota 55905; Facultad de Medicina (Z.H.), Universidad Autónoma de Nuevo León, Nuevo Leon, Mexico; and Mayo Clinic Libraries (L.J.P.), Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008593:Menopause; D009026:Mortality; D016032:Randomized Controlled Trials as Topic; D012306:Risk