title: In older men an optimal plasma testosterone is associated with reduced all-cause mortality and higher dihydrotestosterone with reduced ischemic heart disease mortality, while estradiol levels do not predict mortality.
abstract: BACKGROUND
  Testosterone (T) levels decline with age and lower T has been associated with increased mortality in aging men. However, the associations of its metabolites, dihydrotestosterone (DHT) and estradiol (E2), with mortality are poorly defined.
  
  
  OBJECTIVE
  We assessed associations of T, DHT, and E2 with all-cause and ischemic heart disease (IHD) mortality in older men.
  
  
  METHODS
  Participants were community-dwelling men aged 70 to 89 years who were residing in Perth, Western Australia.
  
  
  METHODS
  Plasma total T, DHT, and E2 were assayed using liquid chromatography-tandem mass spectrometry in early morning samples collected in 2001 to 2004 from 3690 men. Deaths to December 2010 were ascertained by data linkage.
  
  
  RESULTS
  There were 974 deaths (26.4%), including 325 of IHD. Men who died had lower baseline T (12.8±5.1 vs 13.2±4.8 nmol/L [mean±SD], P=.013), DHT (1.4±0.7 vs 1.5±0.7 nmol/L, P=.002), and E2 (71.6±29.3 vs 74.0±29.0 pmol/L, P=.022). After allowance for other risk factors, T and DHT were associated with all-cause mortality (T: quartile [Q] Q2:Q1, adjusted hazard ratio [HR]=0.82, P=.033; Q3:Q1, HR=0.78, P=.010; Q4:Q1, HR=0.86, P>.05; DHT: Q3:Q1, HR=0.76, P=.003; Q4:Q1, HR=0.84, P>.05). Higher DHT was associated with lower IHD mortality (Q3:Q1, HR=0.58, P=.002; Q4:Q1, HR=0.69, P=.026). E2 was not associated with either all-cause or IHD mortality.
  
  
  CONCLUSIONS
  Optimal androgen levels are a biomarker for survival because older men with midrange levels of T and DHT had the lowest death rates from any cause, whereas those with higher DHT had lower IHD mortality. Further investigations of the biological basis for these associations including randomized trials of T supplementation are needed.
authors.affiliation: School of Medicine and Pharmacology (B.B.Y., S.A.P.C., G.J.H., L.F.), University of Western Australia, Perth, Western Australia 6009, Australia; Department of Endocrinology and Diabetes (B.B.Y.), Fremantle Hospital, Fremantle, Western Australia 6160, Australia; Western Australian Centre for Health and Ageing (H.A., O.P.A., L.F.), Centre for Medical Research, University of Western Australia, Perth, Western Australia 6009, Australia; PathWest Laboratory Medicine (S.A.P.C.), Fremantle and Royal Perth Hospitals, Perth, Western Australia 6009, Australia; ANZAC Research Institute (D.J.H.), University of Sydney, Sydney, New South Wales 2139, Australia; School of Psychiatry and Clinical Neurosciences (O.P.A.), University of Western Australia, Perth, Western Australia 6009, Australia; Vascular Biology Unit (J.G.), Queensland Research Centre for Peripheral Vascular Disease, School of Medicine, James Cook University, Townsville, Queensland 4811, Australia; and School of Surgery (P.E.N.), University of Western Australia, Perth, Western Australia 6009, 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: David J
authors.initials: DJ
authors.lastname: Handelsman
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.forename: Osvaldo P
authors.initials: OP
authors.lastname: Almeida
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
authors.forename: Paul E
authors.initials: PE
authors.lastname: Norman
authors.forename: Leon
authors.initials: L
authors.lastname: Flicker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D003940:Diagnostic Techniques, Endocrine / Q000592:standards; D013196:Dihydrotestosterone / Q000097:blood*; D004958:Estradiol / Q000097:blood*; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000175:diagnosis / Q000401:mortality*; D011379:Prognosis; D012015:Reference Standards; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood*; D014904:Western Australia / Q000453:epidemiology
chemical_list: D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol