Human growth hormone

Human growth hormone (HGH) is a natural hormone produced in the pituitary gland, which promotes normal growth and development in the body. It activates protein production in muscle cells and the release of energy from fats. It is typically used to stimulate growth in children with hormone deficiency, or to treat people with severe illnesses, burns or infection where destruction of human tissue and muscle occurs.

A genetically engineered or ‘recombinant’ version of HGH has been produced (rHGH). Test tube experiments have shown that it can stimulate immune cells such as natural killer (NK) cells, which are related to tumour control and T-cells. rHGH is also known as somatrem or somatotropin. One form of HGH is made by Serono under the brand name Serostim, although other forms are made by other manufacturers. It is given as an injection under the skin.

rHGH is a licensed treatment that can be prescribed on the National Health Service for children with short stature as a result of growth hormone deficiency. However, it is not licensed for prescribing to people with HIV in Europe. rHGH is also very expensive to produce, casting doubt on the feasibility of its introduction into routine HIV care.

There has been some concern that the use of human growth hormone in people with HIV would stimulate viral replication and lead to increased viral load. However, recent evidence suggests that individuals who add growth hormone to their anti-HIV combination are likely to experience a small drop in viral load.¹

In HIV disease, HGH is best known as a treatment for HIV-related wasting, although it is not an approved treatment for this condition in Europe. High doses of HGH have been found to increase weight and lean body mass in people with AIDS wasting.^{2 3} An increase in lean body mass is thought to be important in HIV disease because the loss of lean body mass is the form of wasting most closely related to an increased risk of death.

In August 1996, HGH was granted accelerated approval in the United States for the treatment of AIDS wasting. Studies of up to twelve weeks in duration have found that the drug may stabilise weight or reverse weight loss in people with HIV, although no improvements in survival were seen. The long-term safety and tolerability of HGH are unknown. In the European Union, HGH has been granted orphan drug status for the treatment of AIDS wasting, which means that Serono will have exclusive rights to market the product for this purpose in Europe, even though other companies also have their own versions of the treatment.

In a recent meta-analysis of treatments for wasting, rHGH was found to have similar efficacy to the other two major treatments, testosterone and anabolic steroids, with all three showing a significant benefit over placebo. However, rHGH may have advantages in terms of increasing muscle function and quality of life.⁴

Clinical studies, including two randomised trials, have confirmed that HGH can reduce abdominal fat and increase muscle mass in people taking anti-HIV treatment.^{5 6 7 8} These improvements in body composition are paralleled by increases oxygen uptake, the ability to carry out moderate physical exercise, and the capacity for high-intensity exercise.^{9 10}

Reductions in ‘buffalo hump’ and breast size have also been reported, although breast development in men has been noted as a side-effect of rHGH.¹¹ Improvements may reverse on stopping rHGH and may be more likely among individuals with mild body fat abnormalities.

The benefits of rHGH seem to be limited to boosting muscle and decreasing fat accumulation. It has no effect on fat loss in the face and limbs.

In addition to its possible beneficial effects on wasting and fat redistribution, recent studies have suggested that rHGH may improve CD4 cell counts in patients on antiretroviral therapy. In one randomised study addition of 1.5mg rHGH daily to antiretroviral therapy for 48 weeks increased CD4 cell counts by a median of 55 cells/mm³, while a shorter course of 3mg daily for 24 weeks improved CD4 cell counts by the same amount. Around half of this increase was in naive CD4 T-cells and it was coupled with an increase in the size and function of the thymus gland, the organ under the breastbone that produces new naive T-cells.¹²

Further research is needed to establish whether these effects are paralleled by an improved ability to fight infection.

Side-effects of HGH can include headache, muscle pain, joint pain, salt and water retention and rare instances of carpal tunnel syndrome (pain or tingling in the first three or four fingers of the hand). Children treated with the drug over the long term develop antibodies to it, but these do not seem to have any harmful effects.

A large-scale study of rHGH in people with AIDS wasting identified several serious side-effects which were thought to be associated with rHGH. These included skin cancers, gastrointestinal bleeding, inflammation of the arteries, and breast development in men.¹³ Elevated triglycerides and the development of diabetes have also been reported among individuals taking rHGH with antiretroviral therapy-related body fat changes.¹⁴ In a randomised study of several HGH doses to treat AIDS wasting, glucose levels rose modestly in 28% of patients receiving a daily dose and 18% of patients receiving doses on alternate days. There was one case of new onset diabetes and two cases of hyperglycaemia amongst the 646 patients who received HGH for up to 24 weeks.¹⁵.