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Human Growth Hormone Therapy (History, Applications, Controversies, And Risks)

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Human Growth Hormone Therapy

One of the major contributors to proper growth and development of your body is the Growth Hormone (GH) or Human Growth Hormone (hGH).  Also known as somatotropin, this peptide hormone is secreted by the pituitary gland and stimulates growth and cell reproduction. As such, its deficiency can lead to several disorders and ailments. Most noted among them being growth failure, short height, and late sexual maturity.

Human Growth Hormone (hGH) Therapy:

Growth Hormone Deficiency (GDH) is treated by Human Growth Hormone (hGH) therapy. The process involves daily administration of prescribed hGH into the patient’s subcutaneous layer. Today, the therapy is used in several hGH-deficiency as well as non-hGH-deficiency diseases.

Brief History:

Before mid-twentieth century, no work was done to extract pituitary GH for treatment of children with GH-deficiency. Extraction and purification of GH from pigs and cows were done between the late 1940s – early 1950s. The work failed to show any significant result, due to greater species-to-species molecular structure variation.

First growth hormone from the human pituitary gland was acquired in 1956, from a human cadaver. Soon, a trial followed and by 1960, it had been proven that pituitary GH would benefit GH-deficient children. By 1985, several thousands of children in the United States and worldwide were treated for severe GH deficiency.

However, the momentum hit a roadblock when in 1985, the US Food and Drug Administration (US FDA) received reports that four young adults who had been treated with GH in the 1960s developed life-threatening Creutzfeldt-Jakob Disease (CJD). The link was found between CJD and human pituitary GH and on April 19, 1985, its supply was suspended. Subsequently, the use of human pituitary GH quickly declined.

Development of Recombinant Human Growth Hormone (rhGH):

By 1972, the biochemical structure of the hGH became known and the first recombinant human GH (rhGH) was biosynthetically developed in 1981, by Genentech (San Francisco, California). At present, another improved process called protein secretion technology is the most common method used to synthesize rhGH.

The development of rhGH created wide opportunities for in-depth analysis into the possibility of hGH usage in non-hGH-deficient children and other additional indications in adults.

Common Applications of hGH Therapy:

  1. Growth Hormone Deficiency (GHD):

Growth Hormone Deficiency (GDH) may be congenital or develop later in life. There are, almost, no apparent cause in the majority of cases. In severe cases, GHD leads to short stature, delayed growth, slow bone maturation, and slower muscular development. GDH is treated by Growth hormone therapy using daily injections of rhGH.

  1. Chronic Kidney Disease (CKD):

Children with Chronic Kidney Disease (CKD) show severe growth failure and hGH therapy has been acknowledged to combat this. In the case of CKD patients who have not yet reached puberty, hGH treatment improved the final height, depending upon the duration of hGH therapy and extent of initial growth failure. Higher doses than GDH are prescribed for this treatment, which may be stopped after transplantation or may continue. Outcomes are positively better in younger patients who start their treatment earlier and have least renal deterioration.

  1. Turner Syndrome (TS):

Turner Syndrome affects females only, causing exceedingly short stature with height reduction of about 20-22 cm than normal women within their appropriate counterparts. With the application of hGH therapy, cases and studies have shown positive results in the patients suffering from Turner Syndrome.

  1. Prader–Willi syndrome (PWS):

Prader–Willi syndrome (PWS) is the first human disorder linked to genetic imprinting. It is caused due to the changes in the children’s gene expression from their parents. The patients exhibit similar physical abnormality to GHD patients. hGH therapy has induced decreased fat mass, improved heart conditions, increased lean body mass apart from helping linear growth. Early detection is key for better treatment to reduce the effects of the disease.

  1. Small for Gestational Age (SGA):

Small for Gestational Age (SGA) babies are those born with the weight below the 10th percentile for the gestational age, specifically caused by Intrauterine Growth Restriction. A condition where a fetus fails to reach its genetically determined potential size. Irrespective of being premature or not, most SGA babies experience catch-up growth or normalization of their height by 2 or 3 years of age. hGH therapy has shown to accelerate growth and help attain a normal adult height.

  1. Idiopathic Short Stature (ISS):

Idiopathic Short Stature (ISS) is a condition where an individual exhibits height below the average mean of their corresponding age, sex and wider population group, without any apparent abnormalities. hGH therapy enables children with ISS to increase their adult height, minus any unusual issues.

  1. Short Stature Homeobox-Containing Gene (SHOX) Deficiency:

Homeobox gene is a type of genes which regulates development. Short Stature Homeobox-Containing Gene (SHOX) Deficiency is believed to be the main cause of short stature in females with Turner Syndrome. In 2006, the US FDA approved hGH treatment for patients with SHOX deficiency.

  1. Adult Growth Hormone Deficiency:

The US FDA approved hGH treatment of GH-deficient adults in 1996. Clinical studies have shown benefits in body composition, bone density among others. However, long-term observation is required to study for risks such as pituitary tumor recurrence and cancer.

Controversies And Risks:

Since the development of rhGH brought about an unlimited source of growth hormone, several unorthodox and off-label use of hGH have come to light. There have been instances of athletes using human growth hormone to enhance their performance, compelling several athletic bodies to ban its use.

The New England Journal of Medicine in its editorials in 2003 were critical of inappropriate advertising of dietary supplements and use of hGH as an anti-aging agent. It strongly emphasized the insufficient medical and scientific evidence supporting both claims and warned about the unknown dangers of long-term hGH use in healthy adults and geriatric patients.

In one of the controlled small studies, hGH treatment to increase strength and diminish muscle wasting in Intensive Care Unit (ICU) patients, reported inexplicable higher mortality rate for patients who received hGH. Since then, hGH is rarely used in ICU patients except those having extreme growth hormone deficiency.

In 2011, FDA issued a safety alert about a French study, detailing persons treated with rhGH during childhood for certain kinds of short stature were at a small increased risk of death when compared to individuals in the general population of France.

In Conclusion:

There is no denying the fact that hGH therapy is an important treatment and has proved successful in increasing growth and adult height in numerous conditions. However, there is a need for large, multi-center and controlled trials before any conclusion about anti-ageing benefits, increased athletic performance and other indications can be ascertained. And as more and more trials and studies continue to be conducted, it is inevitable that the application of human growth hormone will only continue to expand.

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