Growth hormone (GH, HGH) regulates essential processes such as bone and muscle growth in the body, but as time progresses, the pituitary gland reduces the production of GH. This insufficient production of GH can result in a severe disorder known as growth hormone deficiency (GHD).
Research has underlined the devastating effects of GHD, such as decreased cardiac function, muscle mass, and energy levels. Therefore, researchers have attempted to investigate potential treatment options to increase serum GH levels. One successful method, administration of recombinant GH injections, has become widely used in the treatment of GHD. Despite positive findings, the long-term administration of GH does not come without its potential downfalls. As such, a new study was conducted to investigate the benefits and risks associated with GH therapy in adults with growth hormone deficiency.
Benefits of GH therapy
Growth hormone therapy is linked to various benefits on muscle mass, bone structure, quality of life, cardiac function, and age-related processes.
Recent studies illustrated that administration of GH in individuals resulted in an increase in muscle mass and a reduction in fat compared to placebo. Additionally, a study by Makimura and colleagues demonstrated that in patients with low GH levels and obesity administration of a growth hormone-releasing hormone analog promotes a reduction in visceral fat mass and thickness of the carotid, a significant predictor of coronary disease. Furthermore, a study by Boschetti et al. demonstrated improvement in cardiac function, with a greater capacity for ventricular filling observed after GH therapy in adults with GHD.
Moreover, researchers demonstrated an increase in bone mineral density in growth hormone deficient patients who underwent GH therapy. There have been several associations between GH therapy and quality of life. A study by Giavoli and colleagues supported this finding by demonstrating an improvement in the quality of life scores, especially in the earlier phases of GH therapy. In addition to the above parameters, there has been an improvement in lipid profiles. Prior studies have observed an increase in high-density lipoprotein and reduction in low-density lipoprotein (LDL) after GH therapy.
Researchers attempted to investigate whether aging is associated with the above parameters. A systematic review in patients older than sixty revealed a reduction in LDL, increased muscle mass, decreased visceral fat mass, and improved quality of life. However, no effects were observed in bone mineral density.
Risks of GH therapy
Growth hormone therapy is associated with risks such as increased lipoprotein, adverse events, mortality, diabetes, and neoplasia.
A study conducted by Wieringa and colleagues showed an increase in lipoprotein, an indicator of increased cardiovascular risk, during GH therapy in growth hormone-deficient adults. Other studies have demonstrated significant adverse events such as edema, myalgia, and paresthesias from water retention caused by growth hormone. Researchers demonstrated an increased likelihood of developing such side effects with increasing age and weight. Thus, it is recommended to use each patient’s minimum effective dose to reduce toxic effects during GH treatment. Additionally, the use of low doses can help reduce the increased risk of mortality associated with GH treatment.
Growth hormone therapy is known to increase insulin resistance and blood glucose levels via processes such as gluconeogenesis. A study by Maison et al. revealed an increase in insulin and glucose levels after GH treatment, irrespective of dose or duration of treatment.
Moreover, researchers have taken an extra step to study glucose homeostasis in relation to the increased risk of developing type II diabetes. Multiple studies have demonstrated an increased incidence of diabetes following GH treatment. In addition to the increased risk of diabetes, researchers have suggested an association between GH treatment and increased risk of cancer, especially in children. However, recent data has reported encouraging findings that the relative risk of neoplasia in GH-treated individuals was not increased compared to the control group.
Implications of GHR polymorphism on clinical manifestations and responsiveness to GH therapy
The growth hormone binds to the growth hormone receptors (GHR) that are located on the plasma membrane of target cells. GHR polymorphism has been greatly studied due to the presence of two distinct isoforms that differ by the absence of an exon region (d3), although this absence still renders the protein functional. The deficient isoform of GHR (d3/d3) is considered dominant over the full-length isoform (fl/fl).
Prior studies have alluded that GHR polymorphism can affect the clinical presentation of GHD in adults and the responsiveness to GH therapies. For example, a study by Moyes and colleagues demonstrated significantly increased IGF-1 levels in the deficient exon group compared to the full-length variant after 12 months of treatment. Furthermore, Meyer and colleagues observed that after one year of GH treatment, patients with the d3/d3 genotype required lower GH doses compared to the full-length genotype suggesting increased responsiveness in d3-allele carriers.
However, other studies have shown little to no effect of GHR polymorphism on GH therapy responsiveness. A study by Barbosa et al. demonstrated no significant changes in IGF-1 and body fat after 12 months of GH therapy between the two genotype groups. Likewise, another study by researchers found that the presence of the d3 genotype did not provide individuals with an upper hand in outcomes related to IGF-1 levels, muscle mass, or quality of life.
Given the conflicting evidence, the data is inconclusive to support the role of GHR polymorphism in the clinical presentation and responsiveness of GH treatment in adults with GHD. The importance of the d3 genotype in better responsiveness to GH therapy remains vague.
The question in the scientific community remains: do the benefits outweigh the risks? The study conducted demonstrated indisputable benefits regarding body composition, bone structure, and lipid profiles. However, there is evidence to suggest potential risks associated with GH treatment, such as the increased risk of diabetes and cancer. Nevertheless, it is essential to remain vigilant and to evaluate the associated risk and benefits periodically to prevent any undesirable effects. Future studies should focus on the long-term safety of GH treatment by measuring relevant outcomes such as the incidence of cardiovascular disease, neoplasia, and mortality.