title: Frailty, serum androgens, and the CAG repeat polymorphism: results from the Massachusetts Male Aging Study.
abstract: BACKGROUND
  The CAG repeat polymorphism in the androgen receptor, denoted (CAG)n, is thought to (inversely) index androgen sensitivity. We hypothesized that (CAG)n would exhibit a modifying influence on the association between circulating total and calculated free testosterone (TT and FT) and physical frailty in aging men.
  
  
  OBJECTIVE
  The objective of the study was to establish the influence of (CAG)n on the relation between circulating TT, FT, LH, SHBG, and frailty.
  
  
  METHODS
  This was a prospective cohort study of health and endocrine functioning in randomly selected men, with a baseline (T1: 1987-89) and two follow-up (T2: 1995-1997; T3: 2002-2004) visits.
  
  
  METHODS
  This was an observational study of men residing in greater Boston, MA.
  
  
  METHODS
  A total of 624 subjects aged 50-86 yr were retained.
  
  
  METHODS
  The frailty phenotype was measured at T3. Components included weight loss, exhaustion, low physical activity, weakness, and slowness. Subjects exhibiting two of these five components were considered to be in an intermediate state, and those exhibiting three or more were considered frail.
  
  
  RESULTS
  (CAG)n was positively associated with TT and FT. Multivariable regression analyses revealed no influence of CAG on longitudinal within-subject changes in hormone levels or cross-sectional (T3) associations between hormone concentrations and the prevalence of intermediate frailty or frailty. Models incorporating subjects' history of hormone decline produced similar negative results.
  
  
  CONCLUSIONS
  This population-based study does not support the hypothesis that interindividual differences in (CAG)n can account for a lack of association between circulating androgens and the frailty phenotype. Longitudinal analyses are needed to confirm these conclusions.
authors.affiliation: Department of Epidemiology, New England Research Institutes, 9 Galen Street, Watertown, Massachusetts 02472, USA. ttravison@neriscience.com
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Travison
authors.forename: Rebecca
authors.initials: R
authors.lastname: Shackelton
authors.forename: Andre B
authors.initials: AB
authors.lastname: Araujo
authors.forename: John E
authors.initials: JE
authors.lastname: Morley
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Williams
authors.forename: Richard V
authors.initials: RV
authors.lastname: Clark
authors.forename: John B
authors.initials: JB
authors.lastname: McKinlay
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000728:Androgens / Q000097:blood*; D001827:Body Height / Q000502:physiology; D003430:Cross-Sectional Studies; D016330:Frail Elderly / Q000706:statistics & numerical data*; D005787:Gene Frequency; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008404:Massachusetts; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012959:Socioeconomic Factors; D013739:Testosterone / Q000097:blood; D018911:Trinucleotide Repeats / Q000235:genetics; D015431:Weight Loss / Q000502:physiology
chemical_list: D000728:Androgens; D012739:Gonadal Steroid Hormones; D013739:Testosterone
references.citation: J Appl Physiol (1985). 2005 Jan;98(1):132-7
references.pmid: 15377647
references.citation: J Am Geriatr Soc. 2006 Jun;54(6):991-1001
references.pmid: 16776798
references.citation: J Endocrinol. 1999 Jul;162(1):137-42
references.pmid: 10396030
references.citation: BMC Geriatr. 2008 Oct 13;8:27
references.pmid: 18851754
references.citation: Biometrics. 1982 Dec;38(4):963-74
references.pmid: 7168798
references.citation: J Clin Endocrinol Metab. 2009 Jan;94(1):277-84
references.pmid: 18840639
references.citation: Eur J Endocrinol. 2008 Dec;159(6):739-46
references.pmid: 18805913
references.citation: Cancer. 2007 Dec 15;110(12):2604-13
references.pmid: 17960609
references.citation: J Steroid Biochem. 1982 Jun;16(6):801-10
references.pmid: 7202083
references.citation: Nat Clin Pract Urol. 2008 Jan;5(1):24-34
references.pmid: 18185511
references.citation: J Am Med Dir Assoc. 2008 May;9(4):205-10
references.pmid: 18457793
references.citation: J Clin Endocrinol Metab. 1999 Oct;84(10):3666-72
references.pmid: 10523012
references.citation: J Clin Endocrinol Metab. 2007 Sep;92(9):3604-10
references.pmid: 17579205
references.citation: J Clin Endocrinol Metab. 2003 May;88(5):2049-54
references.pmid: 12727953
references.citation: Gerontology. 2006;52(2):107-10
references.pmid: 16508318
references.citation: J Am Geriatr Soc. 2008 Nov;56(11):2000-8
references.pmid: 19016935
references.citation: J Endocrinol Invest. 2005;28(11 Suppl Proceedings):15-9
references.pmid: 16760619
references.citation: Eur J Endocrinol. 2007 Mar;156(3):395-401
references.pmid: 17322500
references.citation: Int J Androl. 2003 Apr;26(2):76-83
references.pmid: 12641825
references.citation: J Am Geriatr Soc. 2007 Apr;55(4):548-55
references.pmid: 17397433
references.citation: Biol Psychiatry. 2001 Sep 1;50(5):371-6
references.pmid: 11543741
references.citation: J Gerontol A Biol Sci Med Sci. 2009 Jan;64(1):69-75
references.pmid: 19164273
references.citation: J Clin Endocrinol Metab. 2001 Oct;86(10):4867-73
references.pmid: 11600555
references.citation: Trends Endocrinol Metab. 2003 Aug;14(6):289-96
references.pmid: 12890594
references.citation: J Am Geriatr Soc. 1990 Oct;38(10):1105-12
references.pmid: 2229864
references.citation: Front Horm Res. 2009;37:133-149
references.pmid: 19011294
references.citation: Clin Endocrinol (Oxf). 2001 Nov;55(5):659-66
references.pmid: 11894978
references.citation: Int J Androl. 2010 Jun 1;33(3):500-6
references.pmid: 19207614
references.citation: J Gerontol A Biol Sci Med Sci. 2006 Mar;61(3):262-6
references.pmid: 16567375
references.citation: Exp Gerontol. 2004 Jul;39(7):975-84
references.pmid: 15236757
references.citation: J Nutr Health Aging. 2000;4(3):140-2
references.pmid: 10936900
references.citation: Med Clin North Am. 2006 Sep;90(5):837-47
references.pmid: 16962845
references.citation: Urology. 2001 Aug;58(2 Suppl 1):101-7
references.pmid: 11502461
references.citation: Clin Geriatr Med. 1997 Nov;13(4):685-95
references.pmid: 9354749
references.citation: J Clin Epidemiol. 1991;44(7):671-84
references.pmid: 1829756
references.citation: Calcif Tissue Int. 2008 Jun;82(6):427-35
references.pmid: 18484228
references.citation: J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56
references.pmid: 11253156
references.citation: Ann Nutr Metab. 2008;52 Suppl 1:6-11
references.pmid: 18382070
references.citation: Aging Clin Exp Res. 2007 Apr;19(2):145-53
references.pmid: 17446726
references.citation: J Clin Endocrinol Metab. 2009 Oct;94(10):3806-15
references.pmid: 19737923
references.citation: Rev Endocr Metab Disord. 2005 May;6(2):101-8
references.pmid: 15843881
references.citation: J Am Med Dir Assoc. 2007 Nov;8(9):595-603
references.pmid: 17998116