title: Reference ranges and determinants of testosterone, dihydrotestosterone, and estradiol levels measured using liquid chromatography-tandem mass spectrometry in a population-based cohort of older men.
abstract: BACKGROUND
  Testosterone (T) levels decline with increasing age. Controversy exists over the threshold for classifying T as low vs. normal in older men. The relevance of assessing dihydrotestosterone (DHT) and estradiol (E2) remains unclear.
  
  
  OBJECTIVE
  We assessed the associations of T, DHT, and E2 in men aged 70 yr or older and established reference ranges for these in healthy older men.
  
  
  METHODS
  Community-dwelling men aged 70-89 yr residing in Perth, Western Australia, Australia, participated in the study.
  
  
  METHODS
  Plasma T, DHT, and E2 were assayed using liquid chromatography-tandem mass spectrometry in early morning samples from 3690 men.
  
  
  RESULTS
  Increasing age, higher body mass index and waist to hip ratio, dyslipidemia, diabetes, and higher LH were independently associated with lower levels of T and DHT. Increasing age, diabetes, and higher LH were associated with lower E2. In a reference group of 394 men aged 76.1 ± 3.2 yr reporting excellent or very good health with no history of smoking, diabetes, cardiovascular disease, cancer, depression, or dementia, the 2.5th percentile for T was 6.4 nmol/liter (184 ng/dl); DHT, 0.49 nmol/liter; and E2, 28 pmol/liter. Applying these cutoffs to all 3690 men, those with low T or DHT had an increased odds ratio for frailty, diabetes, and cardiovascular disease. Men with both low T and DHT had a higher odds ratio for these outcomes.
  
  
  CONCLUSIONS
  The 2.5th percentile in a reference group of healthy older men provides age-appropriate thresholds for defining low T, DHT, and E2. Additional studies are needed to test their potential applicability and clinical utility in older men.
authors.affiliation: School of Medicine and Pharmacology, Level 2, T Block, Fremantle Hospital, Alma Street, Fremantle, Western Australia 6160, Australia. byeap@cyllene.uwa.edu.au
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: 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; D002853:Chromatography, Liquid; D015331:Cohort Studies; D013196:Dihydrotestosterone / Q000097:blood*; D004958:Estradiol / Q000097:blood*; D006304:Health Status; D006801:Humans; D008297:Male; D012016:Reference Values; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000097:blood*; D014904:Western Australia
chemical_list: D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol