Growth Hormone

Recombinant human growth hormone (rhGH) has been an established therapy for growth hormone deficiency (GHD) in children and adults for more than three decades. ^[1] Growth hormone therapy with rhGH has been recommended for GH-deficient short stature in children, short stature accompanying chronic renal failure prior to renal transplantation, and Turner's syndrome, and is increasingly recommended for adults with GH deficiency following pituitary tumour surgery or irradiation or idiopathic hypopituitarism. ^[2] Growth hormone was initially given as intramuscular injections three times per week, but daily subcutaneous injections were shown to be more effective and have been used since their introduction in the 1980s. ^[1]

Growth hormone, directly and indirectly through local IGF1 and IGF2 production, stimulates bone turnover by increasing osteoblast number and function. ^[3] GH treatment improves height, body composition, bone density, cardiovascular risk factors, physical fitness and quality of life, and the treatment has few side effects in GH-deficient patients. ^[1] Mechanistic links between GH and aging include the evolutionarily conserved insulin/insulin-like growth factor and mechanistic target of rapamycin signaling pathways. ^[4]

Recombinant human GH therapy in Prader-Willi syndrome has been used since its approval in the United States in 2000 and in Europe in 2001. ^[5] Treatment with rhGH promotes longitudinal growth and likely enables children with chronic kidney disease and short stature to reach normal adult height. ^[6] GH treatment of older adults without evidence of pituitary pathology is one of the most controversial issues in aging, and most information comes from studies that are not placebo-controlled. ^[7] Currently, GH treatment in adults is only indicated for individuals with childhood-onset GHD transitioning to adulthood or new-onset GHD due to hypothalamic or pituitary pathologic processes. ^[7] Longevity is not extended in humans with syndromes of GH deficiency or resistance, although the risk of age-related chronic disease is reduced and various indices of increased healthspan have been reported in those individuals. ^[4]

A large excess of GH increases the risk of osteoarthritis and has other serious metabolic side effects. ^[3] Previous studies have implicated growth hormone in the progression of several cancers, including breast, colorectal, and pancreatic, potentially through induction of the epithelial-to-mesenchymal transition. ^[8] The impact of GH on genome maintenance is drastically different in normal compared to cancer cells, consistent with GH promoting aging and cancer progression. ^[9]