title: Extreme concentrations of endogenous sex hormones, ischemic heart disease, and death in women.
abstract: OBJECTIVE
  Sex hormones may be critical determinants of ischemic heart disease and death in women, but results from previous studies are conflicting. To clarify this, we tested the hypothesis that extreme plasma concentrations of endogenous estradiol and testosterone are associated with risk of ischemic heart disease and death in women.
  
  
  RESULTS
  In a nested prospective cohort study, we measured plasma estradiol in 4600 and total testosterone in 4716 women not receiving oral contraceptives or hormonal replacement therapy from the 1981 to 1983 examination of the Copenhagen City Heart Study. During ≤30 years of follow-up, 1013 women developed ischemic heart disease and 2716 died. In women with a plasma estradiol below the fifth percentile compared with between the 10th and 89th percentiles, multifactorially adjusted risk of ischemic heart disease was 44% (95% confidence interval, 14%-81%) higher; however, plasma estradiol concentrations did not associate with death. Also, in women with a plasma testosterone concentration at or above the 95th percentile compared with between the 10th and 89th percentiles, multifactorially adjusted risk was 68% (34%-210%) higher for ischemic heart disease, 36% (18%-58%) higher for any death, and 38% (15%-65%) higher for death from other causes than cardiovascular disease and cancer. These results were similar for postmenopausal women alone.
  
  
  CONCLUSIONS
  In women, extreme low concentrations of endogenous estradiol were associated with high risk of ischemic heart disease, and extreme high concentrations of endogenous testosterone were associated with high risk of ischemic heart disease and death.
authors.affiliation: From the Department of Clinical Biochemistry, Gentofte Hospital (M.B., H.N.H.), Department of Clinical Biochemistry, Herlev Hospital (S.S.V., B.G.N.), Department of Clinical Biochemistry, Rigshospitalet (A.T.-H.), and The Copenhagen City Heart Study, Frederiksberg Hospital (M.B., G.B.J., A.T.-H., B.G.N.), and Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark (M.B., A.T.-H., B.G.N.).
authors.forename: Marianne
authors.initials: M
authors.lastname: Benn
authors.affiliation: From the Department of Clinical Biochemistry, Gentofte Hospital (M.B., H.N.H.), Department of Clinical Biochemistry, Herlev Hospital (S.S.V., B.G.N.), Department of Clinical Biochemistry, Rigshospitalet (A.T.-H.), and The Copenhagen City Heart Study, Frederiksberg Hospital (M.B., G.B.J., A.T.-H., B.G.N.), and Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark (M.B., A.T.-H., B.G.N.).
authors.forename: Sidsel Skou
authors.initials: SS
authors.lastname: Voss
authors.affiliation: From the Department of Clinical Biochemistry, Gentofte Hospital (M.B., H.N.H.), Department of Clinical Biochemistry, Herlev Hospital (S.S.V., B.G.N.), Department of Clinical Biochemistry, Rigshospitalet (A.T.-H.), and The Copenhagen City Heart Study, Frederiksberg Hospital (M.B., G.B.J., A.T.-H., B.G.N.), and Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark (M.B., A.T.-H., B.G.N.).
authors.forename: Haya N
authors.initials: HN
authors.lastname: Holmegard
authors.affiliation: From the Department of Clinical Biochemistry, Gentofte Hospital (M.B., H.N.H.), Department of Clinical Biochemistry, Herlev Hospital (S.S.V., B.G.N.), Department of Clinical Biochemistry, Rigshospitalet (A.T.-H.), and The Copenhagen City Heart Study, Frederiksberg Hospital (M.B., G.B.J., A.T.-H., B.G.N.), and Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark (M.B., A.T.-H., B.G.N.).
authors.forename: Gorm B
authors.initials: GB
authors.lastname: Jensen
authors.affiliation: From the Department of Clinical Biochemistry, Gentofte Hospital (M.B., H.N.H.), Department of Clinical Biochemistry, Herlev Hospital (S.S.V., B.G.N.), Department of Clinical Biochemistry, Rigshospitalet (A.T.-H.), and The Copenhagen City Heart Study, Frederiksberg Hospital (M.B., G.B.J., A.T.-H., B.G.N.), and Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark (M.B., A.T.-H., B.G.N.).
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.affiliation: From the Department of Clinical Biochemistry, Gentofte Hospital (M.B., H.N.H.), Department of Clinical Biochemistry, Herlev Hospital (S.S.V., B.G.N.), Department of Clinical Biochemistry, Rigshospitalet (A.T.-H.), and The Copenhagen City Heart Study, Frederiksberg Hospital (M.B., G.B.J., A.T.-H., B.G.N.), and Faculty of Health and Medical Sciences, University of Copenhagen, København, Denmark (M.B., A.T.-H., B.G.N.). boerge.nordestgaard@regionh.dk.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002423:Cause of Death; D003718:Denmark / Q000453:epidemiology; D015536:Down-Regulation; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013739:Testosterone / Q000097:blood*; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D013739:Testosterone; D004958:Estradiol
keywords: death; epidemiology; estrogens; general social development and population; gonadal steroid hormones; myocardial infarction; myocardial ischemia; testosterone