The purpose of this study is to assess the potential relationships of circulating IGF-I, adrenal and gonadal steroids, and polymorphism ER22/23EK of the glucocorticoid receptor (GC-R) gene with nutritional, functional and cognitive deterioration in a group of elderly people living independently. This is a population-based prospective study with 313 individuals (160 women and 153 men, 76.7±7 years) who participated. A physical exam, evaluation of functional capacity (Barthel scale), cognitive function (minimental state examination-MMSE), geriatric depression scale (GDS), mininutritional assessment (MNA-SF) and cardiometabolic status were performed at basal time point and at 2 years of follow-up. Biological measurements included cortisol, dehydroepiandrosterone (DHEA), DHEA sulphate, testosterone, estradiol, IGF-I and polymorphism ER22/23EK of the GC-R gene.Estradiol was associated with MNA-SF decrease over time (p<0.01, adjusted for age and gender, beta= −0.17, p=0.03). Weight loss was related to testosterone in men (8.6 vs 12.1 pg/ml in no losers; p=0.03), and in women with GDS (13.0% with depression vs 3.3% with no depression; p=0.05) and MMSE (22.2% with cognitive deterioration vs 4.8% with no cognitive deterioration; p=0.049). Barthel decrease was associated with testosterone (p=0.02, after adjusting for age and gender, beta=−0.520, p<0.001), and SHBG (p< 0.01, adjusted for age and gender, beta=0.18, p<0.01). DHEA was associated with deterioration in the MMSE (p=0.01, after adjusting for age, gender, GDS scale and academic status, beta=−0.26, p=0.01). Frailty development was related only in men with testosterone levels at the beginning of the study (p=0.017). ER22/ 23EK was found in 3% of the subjects and carriers had AGE (2012) 34:553-561