title: Prospective longitudinal study of testosterone and incident depression in older men: The Health In Men Study.
abstract: BACKGROUND
  Depression in older men has been associated with low circulating testosterone concentration but data from prospective studies are limited.
  
  
  METHODS
  We conducted a prospective longitudinal study in a community representative cohort of 3179 older men free of clinically significant depressive symptoms at baseline. The main objective of this study was to determine if low serum testosterone, dihydrotestosterone and estradiol concentrations are associated with the development of depressive symptoms. Incident depression was assessed with the Patient Health Questionnaire and via an electronic health record database (The West Australian Data Linkage System). The main exposures of interest were serum testosterone, dihydrotestosterone and estradiol measured by liquid chromatography-mass spectrometry and calculated free testosterone in baseline blood samples (collected between 2001 and 2004).
  
  
  RESULTS
  One hundred and thirty five men (4.2%) developed depression over a median follow up time of 9.4 years (range 8.4-10.9). Men with incident depression were older (median age 77.7 vs 76.1 years, z=-3.82, p=0<0.001) and were more likely to have cardiovascular disease (43.0% vs 32.6%, χ(2)=6.32, p=0.012) and diabetes (22.2% vs 13.2%, χ(2)=8.95, p=0.003). Low serum total testosterone (<6.4 nmol/L) was associated with incident depression (HR 2.07, 95%CI 1.17-3.68) and this remained significant after adjustment for relevant potential confounding factors (HR 1.86, 95%CI 1.05-3.31). Low serum dihydrotestosterone, estradiol and calculated free testosterone were not associated with risk of depression.
  
  
  CONCLUSIONS
  Low serum total testosterone, but not calculated free testosterone, was associated with incident depression in this sample of older men.
authors.affiliation: WA Centre for Health & Ageing, Centre for Medical Research, Harry Perkins Institute of Medical Research & School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia. Electronic address: andrew.ford@uwa.edu.au.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Ford
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia & Department of Endocrinology & Diabetes, Fiona Stanley Hospital, Perth, WA, Australia. Electronic address: bbu.yeap@uwa.edu.au.
authors.forename: Bu B
authors.initials: BB
authors.lastname: Yeap
authors.affiliation: WA Centre for Health & Ageing, Centre for Medical Research, Harry Perkins Institute of Medical Research, University of Western Australia, Perth, WA, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. Electronic address: leon.flicker@uwa.edu.au.
authors.forename: Leon
authors.initials: L
authors.lastname: Flicker
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. Electronic address: graeme.hankey@uwa.edu.au.
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Hankey
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; PathWest Laboratory Medicine, Fremantle and Royal Perth Hospitals, Perth, WA, Australia. Electronic address: paul.chubb@health.wa.gov.au.
authors.forename: S A Paul
authors.initials: SA
authors.lastname: Chubb
authors.affiliation: ANZAC Research Institute, University of Sydney, Concord Hospital, Sydney, NSW, Australia. Electronic address: djh@anzac.edu.au.
authors.forename: David J
authors.initials: DJ
authors.lastname: Handelsman
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University and Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, Queensland, Australia. Electronic address: jonathan.golledge@jcu.edu.au.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
authors.affiliation: WA Centre for Health & Ageing, Centre for Medical Research, Harry Perkins Institute of Medical Research & School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia. Electronic address: osvaldo.almeida@uwa.edu.au.
authors.forename: Osvaldo P
authors.initials: OP
authors.lastname: Almeida
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000453:epidemiology; D016022:Case-Control Studies; D003863:Depression / Q000097:blood* / Q000453:epidemiology*; D013196:Dihydrotestosterone / Q000097:blood; D004958:Estradiol / Q000097:blood; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D054526:Men's Health; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013739:Testosterone / Q000097:blood*
chemical_list: D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol
keywords: Depression; Older men; Testosterone