title: Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts.
abstract: BACKGROUND
  Reference ranges are essential for partitioning testosterone levels into low or normal and making the diagnosis of androgen deficiency. We established reference ranges for total testosterone (TT) and free testosterone (FT) in a community-based sample of men.
  
  
  METHODS
  TT was measured using liquid chromatography tandem mass spectrometry in nonobese healthy men, 19-40 yr old, in the Framingham Heart Study Generation 3; FT was calculated. Values below the 2.5th percentile of reference sample were deemed low. We determined the association of low TT and FT with physical dysfunction, sexual symptoms [European Male Aging Study (EMAS) only], and diabetes mellitus in three cohorts: Framingham Heart Study generations 2 and 3, EMAS, and the Osteoporotic Fractures in Men Study.
  
  
  RESULTS
  In a reference sample of 456 men, mean (sd), median (quartile), and 2.5th percentile values were 723.8 (221.1), 698.7 (296.5), and 348.3 ng/dl for TT and 141. 8 (45.0), 134.0 (60.0), and 70.0 pg/ml for FT, respectively. In all three samples, men with low TT and FT were more likely to have slow walking speed, difficulty climbing stairs, or frailty and diabetes than those with normal levels. In EMAS, men with low TT and FT were more likely to report sexual symptoms than men with normal levels. Men with low TT and FT were more likely to have at least one of the following: sexual symptoms (EMAS only), physical dysfunction, or diabetes.
  
  
  CONCLUSIONS
  Reference ranges generated in a community-based sample of men provide a rational basis for categorizing testosterone levels as low or normal. Men with low TT or FT by these criteria had higher prevalence of physical dysfunction, sexual dysfunction, and diabetes. These reference limits should be validated prospectively in relation to incident outcomes and in randomized trials.
authors.affiliation: Sections of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, Massachusetts, USA. bhasin@bu.edu
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.forename: Michael
authors.initials: M
authors.lastname: Pencina
authors.forename: Guneet Kaur
authors.initials: GK
authors.lastname: Jasuja
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Travison
authors.forename: Andrea
authors.initials: A
authors.lastname: Coviello
authors.forename: Eric
authors.initials: E
authors.lastname: Orwoll
authors.forename: Patty Y
authors.initials: PY
authors.lastname: Wang
authors.forename: Carrie
authors.initials: C
authors.lastname: Nielson
authors.forename: Frederick
authors.initials: F
authors.lastname: Wu
authors.forename: Abdelouahid
authors.initials: A
authors.lastname: Tajar
authors.forename: Fernand
authors.initials: F
authors.lastname: Labrie
authors.forename: Hubert
authors.initials: H
authors.lastname: Vesper
authors.forename: Anqi
authors.initials: A
authors.lastname: Zhang
authors.forename: Jagadish
authors.initials: J
authors.lastname: Ulloor
authors.forename: Ravinder
authors.initials: R
authors.lastname: Singh
authors.forename: Ralph
authors.initials: R
authors.lastname: D'Agostino
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D000328:Adult; D002624:Chemistry, Clinical / Q000592:standards*; D002853:Chromatography, Liquid / Q000592:standards*; D015331:Cohort Studies; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis* / Q000453:epidemiology*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D015995:Prevalence; D012016:Reference Values; D012111:Residence Characteristics; D012307:Risk Factors; D053719:Tandem Mass Spectrometry / Q000592:standards*; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
chemical_list: D013739:Testosterone