Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging in the Chianti Area (InCHIANTI) study.
BACKGROUND
Aging in men is characterized by a progressive decline in levels of anabolic hormones, such as testosterone, insulinlike growth factor 1 (IGF-1), and dehydroepiandrosterone sulfate (DHEA-S). We hypothesized that in older men a parallel age-associated decline in bioavailable testosterone, IGF-1, and DHEA-S secretion is associated with higher mortality independent of potential confounders.


METHODS
Testosterone, IGF-1, DHEA-S, and demographic features were evaluated in a representative sample of 410 men 65 years and older enrolled in the Aging in the Chianti Area (InCHIANTI) study. A total of 126 men died during the 6-year follow-up. Thresholds for lowest-quartile definitions were 70 ng/dL (to convert to nanomoles per liter, multiply by 0.0347) for bioavailable testosterone, 63.9 ng/mL (to convert to nanomoles per liter, multiply by 0.131) for total IGF-1, and 50 microg/dL (to convert to micromoles per liter, multiply by 0.027) for DHEA-S. Men were divided into 4 groups: no hormone in the lowest quartile (reference) and 1, 2, and 3 hormones in the lowest quartiles. Kaplan-Meier survival and Cox proportional hazards models adjusted for confounders were used in the analysis.


RESULTS
Compared with men with levels of all 3 hormones above the lowest quartiles, having 1, 2, and 3 dysregulated hormones was associated with hazard ratios for mortality of 1.47 (95% confidence interval [CI], 0.88-2.44), 1.85 (95% CI, 1.04-3.30), and 2.29 (95% CI, 1.12-4.68), respectively (test for trend, P <.001). In the fully adjusted analysis, only men with 3 anabolic hormone deficiencies had a significant increase in mortality (hazard ratio, 2.44; 95% CI, 1.09-5.46 (test for trend, P <.001).


CONCLUSIONS
Age-associated decline in anabolic hormone levels is a strong independent predictor of mortality in older men. Having multiple hormonal deficiencies rather than a deficiency in a single anabolic hormone is a robust biomarker of health status in older persons.
Maggio
Marcello
M
National Institute on Aging, National Institutes of Health, NIA Clinical Research Branch at Harbor Hospital, 3001 S Hanover Street, Baltimore, MD 21225, USA.
Lauretani
Fulvio
F
Ceda
Gian Paolo
GP
Bandinelli
Stefania
S
Ling
Shari M
SM
Metter
E Jeffrey
EJ
Artoni
Andrea
A
Carassale
Laura
L
Cazzato
Anna
A
Ceresini
Graziano
G
Guralnik
Jack M
JM
Basaria
Shehzad
S
Valenti
Giorgio
G
Ferrucci
Luigi
L
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000032:analysis* / Q000097:blood / Q000652:urine; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood / Q000652:urine; D006304:Health Status; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000652:urine; D007558:Italy; D008297:Male; D009026:Mortality; D011237:Predictive Value of Tests; D013739:Testosterone / Q000032:analysis* / Q000097:blood / Q000652:urine
D015415:Biomarkers; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I