Medical Use of Somatropin (Growth Hormone): Official Indications
Somatropin — recombinant human growth hormone — has been the standard of treatment since 1985 for a number of diseases associated with disorders of growth and metabolism. At the same time, it is precisely this drug that most often becomes surrounded by myths about «rejuvenation» and «sporting advantages». The editorial team has gathered in one article what somatropin is officially registered for, how the diagnosis is made, what contraindications exist and how treatment is monitored.
From the pituitary hormone to a recombinant drug
The first growth hormone preparations were obtained from the pituitary glands of deceased people. Such therapy was used from the late 1950s, but had two significant limitations: a shortage of raw material and the risk of transmitting prion infections. In the mid-1980s, cases of Creutzfeldt-Jakob disease were described in patients who had received pituitary hormone, and its use was stopped in many countries.
Practically simultaneously, recombinant growth hormone appeared, synthesized by genetically modified bacteria. The first such preparation (somatrem, with an additional methionine) was approved in the USA in 1985, and later somatropin appeared with an amino acid sequence completely identical to the human hormone of 191 amino acids.
Today somatropin is produced by several manufacturers under different trade names, in the form of a powder for solution or ready-made cartridges for injection pens. In recent years, long-acting preparations for once-weekly administration have also been registered — somapacitan, somatrogon and lonapegsomatropin — which reduce the burden on patients, especially children.
Despite the variety of forms, the principle of treatment is unchanged: to restore the action of the hormone where it is lacking, or to compensate for specific growth disorders. Somatropin is a prescription drug, and its prescribing in most countries goes through specialized endocrinology centers.
Indications in pediatrics
Most registered indications concern children with growth disorders. The list differs somewhat between the FDA, EMA and national regulators, but the main positions coincide. The clinical guidelines of the Pediatric Endocrine Society (Grimberg et al., 2016) describe in detail when therapy is justified and when its benefit is doubtful.
| Indication | The essence of the problem | Comment |
|---|---|---|
| Growth hormone deficiency | The pituitary does not produce enough hormone | The classic and best-justified indication |
| Turner syndrome | A chromosomal anomaly in girls, short stature | Treatment without confirmed hormone deficiency |
| Prader-Willi syndrome | A genetic syndrome with obesity and hypotonia | Improves body composition; apnea screening is needed |
| Chronic kidney disease | Growth retardation due to metabolic disturbances | Before kidney transplantation |
| Born small for gestational age (SGA) | Absence of catch-up growth | Assessed at a few years of age |
| SHOX gene deficiency, Noonan syndrome | Genetic causes of short stature | Registered in a number of countries |
| Idiopathic short stature | The cause is not established | Approved by the FDA; not registered in Europe |
The goal of pediatric therapy is to bring the child's final height closer to the genetically expected one. Treatment lasts for years and stops when the growth plates in the bones close. After that, some patients are re-examined to determine whether the hormone deficiency persists in adulthood.
Effectiveness depends on the age at the start of therapy, the cause of short stature and adherence to the regimen of daily injections. The best results are achieved with an early start of treatment in children with true hormone deficiency.
In pediatrics the dose is calculated per kilogram of body weight or per body surface area and adjusted depending on the growth rate and the level of IGF-1. These calculations are performed only by a doctor.
Indications in adults
The main indication for adults is confirmed growth hormone deficiency. It may be a continuation of childhood deficiency or arise for the first time as a result of a pituitary tumor, surgery, irradiation, traumatic brain injury or other lesions of the hypothalamic-pituitary region. The guidelines of the Endocrine Society (Molitch et al., 2011) define the procedure for diagnosing and treating such patients.
In adults, hormone deficiency manifests as an increase in visceral fat, a decrease in muscle mass and bone density, an unfavorable lipid profile, reduced physical endurance and poorer quality of life. Replacement therapy partly corrects these changes, although its effect on hard endpoints, such as cardiovascular mortality, has not been definitively proven.
Certain somatropin preparations are registered in the USA for the treatment of HIV-associated wasting (cachexia) and short bowel syndrome. These indications are narrow and are used within the framework of complex treatment.
It is important to distinguish medical indications from the so-called anti-aging practice. A systematic review by Liu and colleagues (2007) regarding healthy elderly people showed only a small decrease in fat mass and an increase in lean mass without improvement in strength or functional indicators, but with an increased frequency of edema, arthralgias and carpal tunnel syndrome. Aging is not a registered indication for somatropin.
Similarly, a review by Liu and colleagues (2008) regarding athletic performance found no convincing evidence of improved strength or endurance in healthy people.
Diagnosis before prescribing
A single blood test for growth hormone is of little value: because of pulsatile secretion, its level at any given moment can be very low even in a healthy person. So the diagnosis of deficiency is made on the basis of stimulation tests and a combination of clinical data.
The gold standard in adults was for a long time considered the insulin tolerance test: artificial hypoglycemia stimulates the release of growth hormone, and an insufficient response indicates deficiency. The test requires constant medical supervision and has contraindications, in particular heart disease and epilepsy.
Alternatives are the glucagon test and the oral test with macimorelin — a ghrelin receptor agonist. A study by Garcia and colleagues (2018) showed that the diagnostic accuracy of macimorelin is comparable to the insulin tolerance test, while the test itself is simpler for the patient.
The level of IGF-1 helps in diagnosis, but a normal value does not rule out deficiency. Instead, IGF-1 is the main marker for selecting the dose and monitoring safety already during treatment.
Contraindications and safety monitoring
The prescribing information for somatropin preparations contains a clear list of situations in which the drug is not prescribed. Some of them are related to the risk of stimulating cell growth, some — to the experience of clinical studies in which harm was found.
- Active malignant neoplasm— any antitumor therapy must be completed before the start of treatment.
- Acute critical illness— in a study by Takala and colleagues (1999), mortality increased in ICU patients on high doses of growth hormone.
- Prader-Willi syndrome with severe obesity or breathing impairment— cases of sudden death have been described.
- Closed growth plates— stimulation of growth in length is impossible.
- Active proliferative diabetic retinopathy.
During treatment, patients regularly undergo tests for IGF-1, glucose and glycated hemoglobin, thyroid hormones and cortisol. Growth hormone can «reveal» hidden hypothyroidism or adrenal insufficiency, so the endocrinologist monitors the entire pituitary axis.
The most common side effects in adults include edema, pain in the joints and muscles, paresthesias and carpal tunnel syndrome. In children, rare but important complications are benign intracranial hypertension, slipped capital femoral epiphysis and progression of scoliosis.
Outside medical indications, somatropin is a doping agent: growth hormone and its releasing factors are in section S2 of the WADA Prohibited List.
Editorial conclusions
Somatropin has a clearly defined list of official indications — from growth hormone deficiency to genetic syndromes and chronic kidney disease in children. For each of them there are clinical guidelines and data from long-term observations.
Prescribing is preceded by careful diagnosis with stimulation tests, and treatment is accompanied by regular laboratory monitoring. Contraindications, such as an active tumor or a critical condition, are based on real clinical data.
The use of somatropin for «rejuvenation» or sporting purposes is not among the official indications and has no convincing evidence base; instead it is associated with side effects and doping sanctions.
We also recommend reading our materials on somatropin and sleep, on IGF-1 as a key laboratory marker and on the medical use of GHRP-2.
References
- Grimberg A, DiVall SA, Polychronakos C, et al. Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016;86(6):361–397.
- Molitch ME, Clemmons DR, Malozowski S, et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587–1609.
- Liu H, Bravata DM, Olkin I, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med. 2007;146(2):104–115.
- Liu H, Bravata DM, Olkin I, et al. Systematic review: the effects of growth hormone on athletic performance. Ann Intern Med. 2008;148(10):747–758.
- Takala J, Ruokonen E, Webster NR, et al. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med. 1999;341(11):785–792.
- Garcia JM, Biller BMK, Korbonits M, et al. Macimorelin as a diagnostic test for adult GH deficiency. J Clin Endocrinol Metab. 2018;103(8):3083–3093.
- Genotropin (somatropin) for injection. Prescribing information. Pfizer; U.S. Food and Drug Administration.
- World Anti-Doping Agency. Prohibited List, section S2: Peptide hormones, growth factors, related substances and mimetics. Montreal: WADA; актуальна редакція.
Andriy Melnyk
A strength-sports coach and author of programs for beginner and intermediate levels. Writes about training planning.
