Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging in the Chianti Area (InCHIANTI) study

Abstract

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.

Figure

Relationship between the number of anabolic hormones in the lowest serum level quartile and 6-year survival in older men. The survival distribution function according to the number of dysregulated hormones is shown for the 6 years of follow-up. The solid black line indicates the survival rates for patients with 0 dysregulated hormones; short-dashed line, survival rates for patients with 1 dysregulated hormone; medium-dashed line, survival rates for patients with 2 dysregulated hormones; and long-dashed line, survival rates for patients with 3 dysregulated hormones. The thresholds for anabolic hormonal deficiency were 70 ng/dL (to convert to nanomoles per liter, multiply by 0.037) for bioavailable testosterone, 63.9 ng/mL (to convert to nanomoles per liter, multiply by 0.13) for total insulinlike growth factor 1, and 60 μg/dL (to convert to micromoles per liter, multiply by 0.027) for dehydroepiandrosterone sulfate (log rank=62.92; P<.001).