Growth Hormone for Weight Loss

 

• What is growth hormone?
• What are the actions of growth hormone?
• Why is growth hormone used to manage obesity?
• How effective is growth hormone in the management of obesity?
• What are the risks of growth hormone use?

What is a hormone?

Hormones are chemicals that are released by cells in the body and are detected by other cells, altering the way they function. They act as ‘chemical messengers’, and play a large role in how the body operates. ‘Artificial’ hormones may be created or synthesised and administered in the form of drugs to treat medical conditions.

What is growth hormone?

Growth hormone (GH) is a hormone produced by the cells of the pituitary gland, a small gland found in the brain. GH production begins early in the womb and continues throughout life, though at a lesser rate. GH release is altered by several factors.

GH secretion is increased by:

• Growth hormone releasing hormone (GHRH), a hormone released by the hypothalamus (a part of the brain);
• Ghrelin, a hormone produced in the gut;
• Fasting;
• High protein meals;
• Low blood sugar levels (hypoglycaemia). Insulin can be used to create low blood sugar levels. In normal circumstances, this would result in increased GH secretion. If this does not occur, GH deficiency may be diagnosed.
• The main female sex hormone oestrogen;
• Other hormones such as dopamine, alpha-adrenergic agonists (released during times of stress) and beta-adrenergic antagonists (beta blockers); and
• Exercise, infection, and trauma.

GH secretion is reduced by:

• Somatostatin, a hormone released by the hypothalamus;
• Insulin like growth factor (IGF-1): This hormone is increased by GH, is responsible for most of the effects of GH, and also reduces the amount of GH released (negative feedback);
• High blood sugar (hyperglycaemia);
• Leptin, a hormone produced by fat cells. It signals to the hypothalamus that the body has had enough to eat;
• Excess glucocorticoids, a type of steroid that may be administered as a drug. High levels of glucocorticoid increase the number of GH receptors on cells. These detect GH, so if there are more of them, the action of GH on cells is greater;
• Beta-2-adrenergic receptor activation. These are a type of receptor that are stimulated by hormones released during times of stress, and also by certain drugs such as adrenaline. If these are activated, GH action is decreased.

GH secretion is at its peak (150 µg/kg) during puberty, and declines by about 50% every seven years to about 25 µg/kg by age 55.

What are the actions of growth hormone?

The main action of GH is to cause the liver to produce a hormone called IGF-1. IGF-1 plays an important role in the growth and development of children. GH acts directly and via IGF-1 to stimulate growth in the long bones of children, such as the thigh bone (femur) and arm bone (humerus).

Metabolic effects of growth hormone include:

• Increased breakdown of stored fat (triglyceride), and increased use of this fat to create energy;
• Counteracting the actions of insulin. Insulin moves sugar from the blood into cells, so GH opposes this;
• Retention (holding in the body) of sodium, phosphate and water; and
• Stimulation of protein production (a large component of muscles).

Too much GH leads to the condition known as acromegaly or gigantism. Growth hormone deficiency may occur in a range of conditions.

Recombinant human GH (rhGH) is a form of artificially produced GH, and may be administered as a drug to manage a range of conditions, such as:

• GH deficiency in adults due to hypothalamic pituitary disease;
• Chronic kidney disease leading to short stature (height);
• Short stature due to Turner’s syndrome or Prader-Willi syndrome;
• HIV-associated wasting in adults; and
• Small for gestational age infants who do not reach sufficient height.

Why is growth hormone used to manage obesity?

Obese individuals are known to have low levels of GH. Growth hormone reduces obesity through its actions on two enzymes which control lipolysis (breakdown of stored triglycerides into free fatty acids) and lipogenesis (fat accumulation). These hormones are lipoprotein lipase (LPL) and hormone sensitive lipase (HSL).

GH reduces the uptake of free fatty acids by adipocytes (fat storage cells). It inhibits LPL, which controls the buildup of triglycerides in fatty tissue. LPL breaks down triglycerides, releasing free fatty acids (FFAs) which may then be taken up by fat cells. GH also encourages the body to use FFAs as an energy source, and to reduce the use of sugars (glucose) and proteins for energy. The impact of GH in reducing LPL activity is greater in fat deposits within the abdomen than in subcutaneous fat. Other hormones that impact on LDL are insulin (increased activity); and catecholamines (dopamine, etc), testosterone and oestrogen (decreased activity).

The presence of circulating FFA reduces the release of GH by the pituitary. The elevation of FFA in obese individuals (due to greater fatty tissue mass) may be partially responsible for the lower levels of GH evident in obesity. There is also increased clearance of GH in obese individuals, through mechanisms that are not well understood. Also, the increased levels of IGF-1 seen in obese individuals has a negative feedback effect on GH release. Finally, the high levels of insulin seen in many obese individuals reduces the release of GH by the pituitary in response to GHRH.

GH assists the action of HSL, which breaks down stored triglycerides into FFAs and glycerol. This allows the use of FFAs as fuel sources elsewhere in the body. The glycerol portion of the triglyceride must be removed in order to enable FFAs to exit the fat cell. GH increases the number of receptors on the cell that recognise hormones that stimulate HSL activity. It also prevents the breakdown of messengers in the cell that allow the effects of HSL to occur.

GH also has a direct impact on the number and maturity of fat cells. Through IGF-1, GH stimulates production of pre-fat cells; however, GH then prevents them from maturing.

GH opposes skeletal muscle breakdown during fasting. When an individual is eating very few calories, GH encourages the use of fat for energy rather than sugar or proteins. This prevents the breakdown of muscle in order to produce proteins for energy.

How effective is growth hormone in the management of obesity?

The effectiveness of GH in reducing obesity is under debate. Some research indicates that it is not effective. One 2003 review stated that “GH administered together with (low calorie) diets did not enhance fat loss or preserve lean tissue mass. No studies provided strong evidence for an independent beneficial effect of GH on visceral adiposity.” Visceral adiposity is fat in and around the abdominal organs. Further, this review reported that most studies found reduced glucose tolerance (the presence of pre-diabetes) associated with the use of GH.

On the other hand, many other studies have reported that GH is effective in reducing fat mass, especially visceral fat. These studies were performed on adults with GH deficiency due to pituitary disease, or low levels of GH associated with obesity in the absence of pituitary disease. One review found that “GH replacement with or without diet and exercise interventions effectively reduces visceral adipose tissue (VAT) and improves lipid abnormalities in GH deficient adults.”²⁴ This review concluded that “GH therapy decreases VAT in subjects with adult GH deficiency and in GH-replete viscerally obese adults. It is generally agreed that adults with GHD and visceral obesity should be given GH replacement therapy. The use of GH, with or without insulin sensitisers, represents a novel, albeit expensive, adjunct to diet and exercise in GH-replete obese individuals who are striving to reduce their cardiovascular risk.”²⁴

A further study showed a small but significant reduction in visceral obesity, and an increase in lean mass and body weight with the administration of GH at physiological (normal for the body) doses. GH administration at high levels was not found to be an effective treatment in viscerally obese subjects. Another study demonstrated a 1.6-fold increase in fat loss due to administration of GH compared with placebo, and concurrent increase in lean body mass.

It has been suggested that the negative results seen in some trials may be due to administration of high doses of GH leading to high levels of insulin. This leads to the formation of fat, which may offset the lipolytic effect of the growth hormone.

What are the risks of growth hormone use?

Side effects of growth hormone administration include:

• Insulin resistance (pre-diabetes)
• Swelling
• Joint pain
• Carpal tunnel syndrome

These are reported to be reversible when treatment with GH is stopped.

There have been some concern that GH use may lead to cancer, particularly if it is given in high doses over long periods of time. A 12–35% increase in pre-cancerous polyps in the colon occurs in patients with acromegaly, and colon cancer occurs in 6.9% of cases. However, it has been suggested that individuals with acromegaly are exposed to higher levels of GH over longer periods of time than would occur with therapeutic GH administration.

Another study reported an increased incidence of leukaemia in children treated with human pituitary GH replacement therapy. Subsequent studies did not confirm this increase. A study published in the Lancet found greater risk of death from Hodgkin’s disease, colorectal cancer and cancer overall in patients treated with human pituitary GH. However, in conjunction with other studies, the authors concluded that, if high-risk groups such as those with chromosomal fragility were excluded, leukaemia risk was not substantially raised.

A recent study designed to further examine this issue analysed the impact of daily GH administration to rats over two years and found no growth of cancer. One expert wrote that it is important to monitor the levels of IGF-1 and IGF-1-binding protein-3 (increased by GH) to ensure therapy resulted in age appropriate limits. IGF-1 prevents cell death, and may therefore prevent the death of cells with mutations which may become cancer cells.

More information

For more information on obesity, health and social issues, and methods of weight loss, as well as some useful tools, see Weight Loss.

 

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