GROWTH HORMONE BEYOND SOMATIC GROWTH: EFFECTS OF THE GH/IGF-1 AXIS ON COGNITION, MOOD, AND METABOLIC HEALTH IN ADULT GROWTH HORMONE DEFICIENCY

Abstract

Growth hormone (GH) is classically defined by its role in linear growth, yet the GH/insulin-like growth factor-1 (IGF-1) axis is increasingly recognized as an important regulator of central nervous system function. This study examined cognitive, affective, and metabolic correlates of the GH/IGF-1 axis in adults with growth hormone deficiency (AGHD) and tested whether recombinant human GH replacement improves these outcomes. In a quasi-experimental design, 104 adults with AGHD and 104 age- and sex-matched healthy controls underwent neuropsychological testing, mood assessment, and metabolic profiling; a randomized subsample of AGHD patients (n=102) received GH or placebo for 24 weeks. At baseline, AGHD patients had markedly lower serum IGF-1 (96 vs 182 ng/mL; p<.001) and showed impairments across cognitive domains, most prominently in processing speed (z=-0.62). Serum IGF-1 correlated with processing speed across the full sample (r=0.46, p<.001). GH replacement raised IGF-1 into the normal range, improved cognitive z-scores, reduced depressive symptoms relative to placebo (group × time F(4,404)=7.8, p<.001), and produced favorable changes in body composition and lipid profile, including a 9.8% reduction in fat mass. These findings indicate that the GH/IGF-1 axis contributes to cognition, mood, and metabolic regulation well beyond childhood growth and that its restoration confers measurable neurocognitive and metabolic benefit in deficient adults. (All data are simulated for methodological demonstration and do not derive from human participants.)