title: The association of obesity with sex hormone-binding globulin is stronger than the association with ageing--implications for the interpretation of total testosterone measurements.
abstract: OBJECTIVE
  Total testosterone concentrations are influenced by sex hormone-binding globulin (SHBG) concentrations, which are decreased by obesity and increased with ageing. Therefore, we sought to understand and compare the associations of ageing and obesity with SHBG.
  
  
  METHODS
  We performed a retrospective, cross-sectional analysis of the associations of obesity and age on SHBG and testosterone measurements in men being evaluated for hypogonadism.
  A total of 3671 men who underwent laboratory testing for testosterone deficiency from the Veterans Administration Puget Sound Health Care System from 1997 through 2007 was included. Univariate and multivariate linear regression modelling of the associations between age and body mass index (BMI) and SHBG was performed.
  
  
  RESULTS
  Obesity was associated with a significantly lower SHBG [β = -1·26 (95% CI -1·14, -1·38) nmol/l] per unit increase in BMI. In contrast, ageing was associated with a significantly increased SHBG [β = 0·46 (95% CI 0·39, 0·53) nmol/l per year] (P < 0·001 for both effects). The association of obesity with lower SHBG was two to three times larger than the association of ageing with increased SHBG in both univariate and multivariate modelling. On average, obese men (BMI >30 kg/m(2)) had significantly lower SHBG and total testosterone concentrations than nonobese men [(mean ± SD) SHBG: 36 ± 22 vs 50 ± 27 nmol/l and total testosterone: 10·5 ± 5·4 nmol/l vs 14·1 ± 7·4 nmol/l; (P < 0·001 for both comparisons)], but calculated free testosterone concentrations did not differ between obese and nonobese men.
  
  
  CONCLUSIONS
  We found that the association between obesity and lowered SHBG is greater than the association of ageing with increased SHBG. These competing effects may impact total testosterone measurements for the diagnosis of low testosterone, particularly in obese men.
authors.affiliation: Center for Research in Reproduction and Contraception, University of Washington, Seattle, WA, USA.|Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Cooper
authors.affiliation: Center for Research in Reproduction and Contraception, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Page
authors.affiliation: Center for Research in Reproduction and Contraception, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Amory
authors.affiliation: Center for Research in Reproduction and Contraception, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Anawalt
authors.affiliation: Center for Research in Reproduction and Contraception, University of Washington, Seattle, WA, USA.|Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Matsumoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D012189:Retrospective Studies; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000097:blood; D055815:Young Adult
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone