Growth hormone (GH) is frequently surreptitiously used to improve athletic performance or to stop or reverse the effects of aging. While the US Food and Drug Administration (FDA) has approved GH treatment for specific conditions, the off-label use of GH is illegal in the United States and may be associated with significant risks.1

A position statement2 by the American Association of Clinical Endocrinologists (AACE) published in Endocrine Practice is focused on the issue of off-label use and misuse of various hormones and supplements, including the misuse of GH.

Background

Human cadaveric GH was used initially in medical treatments but has been replaced by recombinant GH preparations produced using recombinant DNA methodology. However, human cadaveric GH may still be available on the black market.2

In recent years, there has been a significant surge in the misuse of GH.2 Several factors are at fault, including unfounded advertisements and websites supporting its use to improve energy and muscle strength, as well as claims made by unauthorized self-proclaimed specialists in support of the use of GH to alleviate various symptoms.2


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Approved Uses for Growth Hormone

Treatment with GH is approved by the FDA for indications in both children and adults. The approved indications for recombinant GH include short stature secondary to GH deficiency, Turner syndrome, Noonan syndrome, Prader-Willi syndrome, short stature homeobox-containing gene (SHOX) gene deficiency, chronic renal insufficiency, and idiopathic short stature.1 Use of GH is also approved for short stature in children born small for gestational age without catch-up growth.1

The Endocrine Society guidelines for evaluation and management of adult GH deficiency recommend completing an insulin tolerance test and GH-releasing hormone-arginine test, or a glucagon stimulation test when these are not available, to establish a diagnosis of GH deficiency. However, there is no need for this formal testing to confirm the diagnosis in some cases, such as in children with structural lesions and multiple hormone deficiencies or a known genetic etiology.3 In these patients, documenting low levels of insulin-like growth factor-1 (IGF-1) is sufficient.

In the presence of GH deficiency, treatment with GH has significant clinical benefits, including improvement in quality of life, body composition, bone mineral density, serum lipid levels, and exercise ability. However, GH treatment is contraindicated in patients with an active malignancy and may require adjustments in patients receiving treatment for diabetes mellitus.3

Treatment with GH should be started at low doses and titrated in each patient according to clinical response, levels of IGF-1, and side effects.3

Off-Label Use of Growth Hormone

According to the Crime Control Act of 1990, off-label use of GH in the United States is illegal. GH has been included in the prohibited list of substances promulgated by the World Anti-Doping Agency.2

There has been much attention given to GH abuse in competitive sports, and evidence suggests nonprescription use of GH is not uncommon among adolescents and adults aiming to enhance physical and athletic performance. However, data in support of the effects of GH on athletic performance in healthy individuals are limited.2 In many cases, GH is combined with other anabolic agents and is not used alone, further limiting the ability to assess its independent effects in healthy users.2

While there are claims that GH is a potential anti-aging hormone that can prevent body composition changes and physical decline associated with the aging process, there is no evidence that treatment with GH in older adults improves body function.2

Risks Associated With Use of Growth Hormone

While the approved use of GH is generally regarded as quite safe, there are concerns regarding the potential for cancer risk and tumor regrowth, although several studies have shown no effect of GH treatment on tumor regrowth or recurrence.3 A 2018 systematic review and meta-analysis to assess GH therapy in childhood cancer survivors did not show increased risk for recurrence or secondary tumors.4

The most common side effects of GH therapy are associated with fluid retention and include paresthesia, peripheral edema, arthralgia, myalgia, and sweating. Other potential adverse effects may include increased blood pressure, intracranial hypertension, gynecomastia, worsening of glucose tolerance, and retinopathy. Most of these adverse effects are dose-related and more common in older adults.2,3

Use of cadaveric GH from the black market may be associated with an increased risk for Creutzfeldt-Jakob disease.2

Most data on the potential adverse effects associated with GH therapy are based on studies of GH replacement in GH-deficient subjects, and there are no available studies on the potential harms of GH misuse, during which GH is often used in supraphysiologic doses and regimens that may be more hazardous.2 Acromegaloid features may develop with prolonged use of GH in large doses and may be associated with increased mortality risk.2,3

Another important factor to keep in mind is the high cost of GH treatment, especially for those who use high GH doses on a daily basis. In addition to the direct cost of GH treatment, there are also additional indirect healthcare costs secondary to the morbidity associated with excess GH use.2

Recommendations for Healthcare Professionals

The AACE strongly recommends a diagnosis of GH deficiency be made by a board-certified endocrinologist and subsequently confirmed by careful review of a patient’s test results. Endocrinologists and other adult healthcare practitioners should be prepared to lead discussions with patients regarding the unfavorable balance between risks and benefits associated with off-label GH use.2

“Given the rise of health-care costs associated with tests and medications, practitioners should strive to be good stewards of the health-care system by minimizing the ordering of unnecessary tests and medications. Treatment recommendations should be based upon well-designed scientific studies. Finally, we should always keep in mind one of the most important principles of medicine, which is to do no harm,” concluded the experts who authored the AACE statement.2

Disclosure: Several authors of the AACE position statement2 declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

1. Somatropin information. US Food and Drug Administration. Updated July 23, 2015. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/somatropin-information

2. Irwig MS, Fleseriu M, Jonklaas J, et al. Off-label use and misuse of testosterone, growth hormone, thyroid hormone, and adrenal supplements: risks and costs of a growing problem. Endocr Pract. 2020;26(3):340-353.

3. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587-1609.

4. Tamhane S, Sfeir JG, Kittah NEN, et al. GH therapy in childhood cancer survivors: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2018;103(8):2794-2801.