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The Aging in the Chianti Area (InCHIANTI) Study

Marcello Maggio, MD; Fulvio Lauretani, MD; Gian Paolo Ceda, MD; Stefania Bandinelli, MD; Shari M. Ling, MD; E. Jeffrey Metter, MD; Andrea Artoni, MD; Laura Carassale, MD; Anna Cazzato, MD; Graziano Ceresini, MD; Jack M. Guralnik, MD; Shehzad Basaria, MD; Giorgio Valenti, MD; Luigi Ferrucci, MD, PhD

Arch Intern Med. 2007;167(20):2249-2254.

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 µg/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.

Author Affiliations: Department of Internal Medicine and Biomedical Sciences, Section of Geriatrics, University of Parma, Parma, Italy (Drs Maggio, Ceda, Artoni, Carassale, Cazzato, Ceresini, and Valenti); Tuscany Regional Health Agency (Dr Lauretani) and Geriatric Rehabilitation Unit, ASF-Florence (Dr Bandinelli), Florence, Italy; Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging Intramural Research Program, National Institutes of Health (Drs Ling, Metter, Basaria, and Ferrucci), and Department of Medicine, Division of Endocrinology, Johns Hopkins University School of Medicine, Bayview Medical Center (Dr Basaria), Baltimore, Maryland; and Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland (Dr Guralnik).

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