Frailty, serum androgens, and the CAG repeat polymorphism: results from the Massachusetts Male Aging Study.
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.
Travison
Thomas G
TG
Department of Epidemiology, New England Research Institutes, 9 Galen Street, Watertown, Massachusetts 02472, USA. ttravison@neriscience.com
Shackelton
Rebecca
R
Araujo
Andre B
AB
Morley
John E
JE
Williams
Rachel E
RE
Clark
Richard V
RV
McKinlay
John B
JB
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
D000728:Androgens; D012739:Gonadal Steroid Hormones; D013739:Testosterone
J Appl Physiol (1985). 2005 Jan;98(1):132-7
15377647
J Am Geriatr Soc. 2006 Jun;54(6):991-1001
16776798
J Endocrinol. 1999 Jul;162(1):137-42
10396030
BMC Geriatr. 2008 Oct 13;8:27
18851754
Biometrics. 1982 Dec;38(4):963-74
7168798
J Clin Endocrinol Metab. 2009 Jan;94(1):277-84
18840639
Eur J Endocrinol. 2008 Dec;159(6):739-46
18805913
Cancer. 2007 Dec 15;110(12):2604-13
17960609
J Steroid Biochem. 1982 Jun;16(6):801-10
7202083
Nat Clin Pract Urol. 2008 Jan;5(1):24-34
18185511
J Am Med Dir Assoc. 2008 May;9(4):205-10
18457793
J Clin Endocrinol Metab. 1999 Oct;84(10):3666-72
10523012
J Clin Endocrinol Metab. 2007 Sep;92(9):3604-10
17579205
J Clin Endocrinol Metab. 2003 May;88(5):2049-54
12727953
Gerontology. 2006;52(2):107-10
16508318
J Am Geriatr Soc. 2008 Nov;56(11):2000-8
19016935
J Endocrinol Invest. 2005;28(11 Suppl Proceedings):15-9
16760619
Eur J Endocrinol. 2007 Mar;156(3):395-401
17322500
Int J Androl. 2003 Apr;26(2):76-83
12641825
J Am Geriatr Soc. 2007 Apr;55(4):548-55
17397433
Biol Psychiatry. 2001 Sep 1;50(5):371-6
11543741
J Gerontol A Biol Sci Med Sci. 2009 Jan;64(1):69-75
19164273
J Clin Endocrinol Metab. 2001 Oct;86(10):4867-73
11600555
Trends Endocrinol Metab. 2003 Aug;14(6):289-96
12890594
J Am Geriatr Soc. 1990 Oct;38(10):1105-12
2229864
Front Horm Res. 2009;37:133-149
19011294
Clin Endocrinol (Oxf). 2001 Nov;55(5):659-66
11894978
Int J Androl. 2010 Jun 1;33(3):500-6
19207614
J Gerontol A Biol Sci Med Sci. 2006 Mar;61(3):262-6
16567375
Exp Gerontol. 2004 Jul;39(7):975-84
15236757
J Nutr Health Aging. 2000;4(3):140-2
10936900
Med Clin North Am. 2006 Sep;90(5):837-47
16962845
Urology. 2001 Aug;58(2 Suppl 1):101-7
11502461
Clin Geriatr Med. 1997 Nov;13(4):685-95
9354749
J Clin Epidemiol. 1991;44(7):671-84
1829756
Calcif Tissue Int. 2008 Jun;82(6):427-35
18484228
J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56
11253156
Ann Nutr Metab. 2008;52 Suppl 1:6-11
18382070
Aging Clin Exp Res. 2007 Apr;19(2):145-53
17446726
J Clin Endocrinol Metab. 2009 Oct;94(10):3806-15
19737923
Rev Endocr Metab Disord. 2005 May;6(2):101-8
15843881
J Am Med Dir Assoc. 2007 Nov;8(9):595-603
17998116