title: In older men, higher plasma testosterone or dihydrotestosterone is an independent predictor for reduced incidence of stroke but not myocardial infarction.
abstract: BACKGROUND
  Older men have lower T levels, but whether differences in circulating T or its metabolites dihydrotestosterone (DHT) or estradiol (E2) contribute to cardiovascular disease remains controversial.
  
  
  OBJECTIVE
  We tested the hypothesis that plasma T, DHT, and E2 are differentially associated with the incidence of myocardial infarction (MI) and stroke in older men.
  
  
  METHODS
  Plasma total T, DHT, and E2 were assayed using liquid chromatography-mass spectrometry in early-morning samples from 3690 community-dwelling men aged 70-89 years. Outcomes of the first hospital admission or death due to MI or stroke were ascertained by data linkage.
  
  
  RESULTS
  Mean follow-up was 6.6 years. Incident MI occurred in 344, stroke in 300, and neither in 3046 men. In a multivariate analysis adjusting for age and other risk factors, T, DHT, and E2 were not associated with incident MI [fully adjusted hazard ratio (HR) for T in quartile (Q) 4 vs Q1: 0.92, 95% confidence interval (CI) 0.66-1.28; DHT: 0.83, 95% CI 0.59-1.15; E2: 0.84, 95% CI 0.62-1.15]. Higher T or DHT was associated with a lower incidence of stroke (T: Q4: Q1 fully adjusted HR 0.56, 95% CI 0.39-0.81, P = .002; DHT: 0.57, 95% CI 0.40-0.81, P = .002). E2 was not associated with stroke (HR 0.76, 95% CI 0.54-1.08, P = .123).
  
  
  CONCLUSIONS
  Higher plasma T or DHT is a biomarker for reduced risk of stroke but not MI. Androgen exposure may influence outcomes after rather than the incidence of MI, whereas androgens but not E2 are independent predictors of stroke risk. Randomized clinical trials are needed to clarify the impact of modifying T or DHT on the risk of stroke in aging men.
authors.affiliation: School of Medicine and Pharmacology (B.B.Y., S.A.P.C., G.J.H., L.F.), Western Australian Centre for Health and Ageing (H.A., O.P.A., L.F.), Centre for Medical Research, School of Psychiatry and Clinical Neurosciences (O.P.A.), and School of Surgery (P.E.N.), University of Western Australia, Perth, Western Australia 6009, Australia; Department of Endocrinology and Diabetes (B.B.Y.), Fremantle and Fiona Stanley Hospitals, Perth, Western Australia 6160, Australia; School of Public Health (H.A.), Curtin University, Perth, Western Australia 6102, Australia; PathWest Laboratory Medicine (S.A.P.C.), Fremantle and Royal Perth Hospitals, Perth, Western Australia 6160, Australia; ANZAC Research Institute (D.J.H.), University of Sydney, Sydney, New South Wales 2139, Australia; Vascular Biology Unit (J.G.), Queensland Research Centre for Peripheral Vascular Disease, School of Medicine, James Cook University, Brisbane, Queensland 4811, Australia; and Department of Vascular and Endovascular Surgery (J.G.), Townsville Hospital, Townsville, Queensland 4814, Australia.
authors.forename: Bu B
authors.initials: BB
authors.lastname: Yeap
authors.forename: Helman
authors.initials: H
authors.lastname: Alfonso
authors.forename: S A Paul
authors.initials: SA
authors.lastname: Chubb
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: David J
authors.initials: DJ
authors.lastname: Handelsman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
authors.forename: Osvaldo P
authors.initials: OP
authors.lastname: Almeida
authors.forename: Leon
authors.initials: L
authors.lastname: Flicker
authors.forename: Paul E
authors.initials: PE
authors.lastname: Norman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D013196:Dihydrotestosterone / Q000097:blood*; D004958:Estradiol / Q000097:blood; D006801:Humans; D015994:Incidence; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology*; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D020521:Stroke / Q000453:epidemiology*; D013739:Testosterone / Q000097:blood*; D014904:Western Australia / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone