Growth hormone (somatropin) in aging

Growth hormone (GH, somatropin) is a peptide hormone secreted by the anterior pituitary that regulates body composition, bone density, and metabolism primarily through hepatic production of insulin-like growth factor 1 (IGF-1). After the third decade, GH pulse amplitude and daily secretion decline roughly 14% per decade — termed somatopause — leading to reduced IGF-1, increased visceral adiposity, and loss of lean mass. The landmark Rudman 1990 trial (NEJM) showed six months of recombinant GH in 21 men aged 61–81 increased lean body mass by 8.8% and reduced adipose tissue by 14.4%; Rudman himself cautioned the study had no anti-aging implications. A central paradox complicates the picture: in C. elegans, Drosophila, and multiple mouse strains (Ames dwarf, Snell dwarf, GH-receptor knockout), reduced GH/IGF-1 signaling extends lifespan by 40–65%, while humans with Laron syndrome (congenital GH-receptor deficiency) show near-zero cancer incidence and diminished diabetes risk despite severe short stature. In older adults, GH replacement improves body composition but has not demonstrated benefits in functional capacity, cognition, or survival, and carries substantial risks — insulin resistance, fluid retention, arthralgias, carpal tunnel syndrome, and a theoretical increase in cancer promotion via IGF-1-driven mitogenic signalling. Aguiar-Oliveira and Bartke (Endocrine Reviews 2019) concluded that current evidence does not support off-label GH use for healthy aging; approved indications remain restricted to documented adult GH deficiency of pituitary origin.