Nonandrogenic Anabolic Hormones Predict Risk of Frailty: European Male Ageing Study Prospective Data

Context Low levels of nonandrogenic anabolic hormones have been linked with frailty, but evidence is conflicting and prospective data are largely lacking. Objective To determine associations between nonandrogenic anabolic hormones and prospective changes in frailty status. Design/Setting A 4.3-year prospective observational study of community-dwelling men participating in the European Male Ageing Study. Participants Men (n = 3369) aged 40 to 79 years from eight European centers. Main Outcome Measures Frailty status was determined using frailty phenotype (FP; n = 2114) and frailty index (FI; n = 2444). Analysis Regression models assessed relationships between baseline levels of insulinlike growth factor 1 (IGF-1), its binding protein 3 (IGFBP-3), dehydroepiandrosterone sulfate (DHEA-S), 25-hydroxyvitamin D (25OHD), and parathyroid hormone (PTH), with changes in frailty status (worsening or improving frailty). Results The risk of worsening FP and FI decreased with 1 standard deviation higher IGF-1, IGFBP-3, and 25OHD in models adjusted for age, body mass index, center, and baseline frailty [IGF-1: odds ratio (OR) for worsening FP, 0.82 (0.73, 0.93), percentage change in FI, -3.7% (-6.0, -1.5); IGFBP-3: 0.84 (0.75, 0.95), -4.2% (-6.4, -2.0); 25OHD: 0.84 (0.75, 0.95); -4.4%, (-6.7, -2.0)]. Relationships between IGF-1 and FI were attenuated after adjusting for IGFBP-3. Higher DHEA-S was associated with a lower risk of worsening FP only in men >70 years old [OR, 0.57 (0.35, 0.92)]. PTH was unrelated to change in frailty status. Conclusions These longitudinal data confirm the associations between nonandrogenic anabolic hormones and the changes in frailty status. Interventional studies are needed to establish causality and determine therapeutic implications.