Growth Hormone: A review of the literature

BRAIN AND SPINAL CORD INJURIES

Hormonal imbalances, including but not limited to growth hormone (GH) deficiencies, are recognised complications of significant traumas, in particular spinal cord damage and head injuries.


Effect of growth hormone replacement therapy on cognition after traumatic brain injury (2010)

In this study, the effects of GH supplementation were assessed in patients who experienced hormone deficiency following a traumatic brain injury. Objective neuropsychological and functional testing was conducted before and after the treatment. A statistically significant improvement in the outcomes of these tests was observed, suggesting that hormone supplementation can actually reverse cognitive impairment. Furthermore, no untoward side effects from the treatment were observed. (1)


Growth hormone (GH) and brain trauma (2013)

Devesa et al. conducted a case series studying the co-administration of GH together with rehabilitation in the recovery of traumatic brain injury (TBI) patients. All the patients in the report had been treated for several years using standard rehabilitation protocol, without significant improvement. GH was administered for a period up to 8 months, in conjunction with continuing rehabilitation. All cases demonstrated significant improvement in cognitive and motor skills, including swallowing and visual performance. These improvements were independent of whether the patient had an acquired GH-deficiency as a result of TBI. This suggests that GH administration can be beneficial in all patients who experience cognitive and motor impairment as a result of TBI, regardless of whether or not they are GH deficient. No adverse effects were observed. (2)

MUSCULOSKELETAL INJURIES

The clinical benefits of GH extend beyond hormonal regulation. GH has a growing evidence base for use in severe traumas and significant musculoskeletal injuries. The literature suggests that GH would expedite, and maintain, recovery from commonly sustained physical traumas.


Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis (2010)

Extracellular matrix contributes important tensile properties to skeletal and musculotendinous tissue, and its regeneration following injury is vital. Doessing et al. sought to assess the role that GH administration has in the promotion of matrix synthesis by investigating the effects of a 14-day course of recombinant human GH (rhGH) in healthy young individuals. Their results showed that GH administration resulted in a 5.8-fold increase in muscle collagen protein synthesis, and a 1.3-fold increase in tendon collagen protein synthesis. Myofibrillar protein synthesis was unaffected. These results suggest that GH is more biologically important in strengthening the matrix tissue, than for muscle cell hypertrophy. From this it may be inferred that hGH is more valuable in the treatment of injuries than for sporting enhancement. (3)


Growth factors improve muscle healing in vivo (2000)

Menetrey et al. aimed to assess the roles of various growth factors on muscle healing. The study evaluated the effect of local injections into a region of lacerated muscle, comparing IGF-1 solution with a physiological solution of an equivalent volume. The results showed that local injection of IGF-1 led to increased muscle regeneration at one month, in both deep and superficial portions of the muscle. The fast-twitch strength and tetanus strength of the treated muscle was also increased, by 36% and 34% respectively. These results are of interest due to the stimulatory effects of GH on the production IGF-1, and the fact that systemic administration of GH results in elevated serum levels of IGF-1. (4)


Intra-articular growth hormone injections regrow cartilage, increase motion and reduce pain in 93 per cent. of arthritic ankles (2012)

This case series assessed the effects of intra-articular GH injections as a treatment for advanced osteoarthritis of the ankle. Injections were given weekly for a period of 5 to 12 weeks, and were supplemented with gentle rehabilitation. 93% of patients experienced excellent results, with an average pain reduction of 5/10. Range of motion of the ankle increased by an average of 14º, where baseline motion ranged from 0º to 30º. No side effects, complications or infections developed throughout the treatment. (5)


Systemic application of growth hormone enhances the early healing phase of osteochondral defects--a preliminary study in micropigs (2003)

One of the most commonly encountered clinical conditions is impaired osteochrondral healing following a traumatic injury, ultimately leading to osteoarthritis. Bail et al. assessed the effects of systemically administered GH on chondral defects when compared with placebo (sodium chloride). The results of the study demonstrated that the GH supplementation group showed better healing (measured on histomorphology with the Wakitani score), a more rapid advance to cartilage maturation, and an increased percentage of defect filling. (6)


Morphoangiogenesis: a unique action of growth hormone (2002)

In microvascular research, Dunn described a phenomenon known as morphoangiogenesis. He observed that intra-articular GH injections caused mature subchondral arteries to rejuvenate and form fenestrated capillaries and cartilage canals, the structures that form the foetal cartilage skeleton. The process is characterised by in vivo stem cell production and articular cartilage regeneration. These findings support the use of GH as a treatment for articular cartilage degeneration, as seen in osteoarthritis and chondral trauma. (7)


Homologous growth hormone accelerates healing of segmental bone defects (2001)

GH has also been found valuable in secondary fracture healing, a phase characterised by regrowth of bone, rather than scar formation. Raschke et al. demonstrated that the effect of daily subcutaneous GH supplementation during the healing process resulted in increased torsional failure load and stiffness of the defect, by 70% and 83% respectively. This ultimately leads to improved post-fracture functionality and endurance. These findings were statistically significant. A significant increase in insulin-like growth factor (IGF-1) was also observed in the treatment group, suggesting that the effects are endocrinologically mediated. (8)


Effects of growth hormone in patients with tibial fracture: a randomised, double-blind, placebo-controlled clinical trial (2007)

Raschke et al. have also investigated the effects of GH in patients with tibial fractures, an injury that is typically slow-healing and associated with frequent complications. Subgroup analysis demonsrated a 26% decrease in the healing time of closed tibial fractures, when treated with subcutaneous GH for 16 weeks following surgical repair. (9)


Support of the metabolic response to burn injury (2004)

Severe burn injuries cause the body to adopt a hypercatabolic state, leading to increased morbidity and mortality. GH is an anabolic agent, and has been shown to ameliorate some of the deleterious effects of hypermetabolism. Daily administration of rhGH to burns victims reduced wound healing time by 25% when compared with the average healing time. The quality of the healing was also improved, with no increase in the rate of scarring. A corresponding increase of 100% in serum levels of IGF-1 was also noted. (10)

COMPETITIVE SPORT

GH is commonly perceived as a performance-enhancing agent and is reportedly widely abused in professional and amateur sporting circles. It is classified as a prohibited substance on the World Anti-Doping Agency (WADA) Prohibited List. Purported properties include ergogenicity, injury recovery and undetectability.


Growth hormone doping in sports: a critical review of use and detection strategies (2012)

In this paper, Baumann conducts a comprehensive review of the structure, function, and regulation of growth hormone, as well as common strategies used for detection of exogenous supplementation. In contrast to the commonly held belief that GH is undetectable as a doping agent, two common methods are used to detect GH in the blood stream: the GH isoform test and the biomarker test. While these have limitations and the detection remains challenging, research continues to identify more specific and useful methods.


The review also discusses the performance enhancing qualities, or ergogenicity, of exogenous GH. Despite the fact that GH appears to be the ideal ergogenic agent, the evidence for performance enhancement is weak. The complexity of the endocrine system makes assessment of the ergogenicity challenging, and results remain equivocal. As discussed above (Doessing et al.), use of GH appears to be more beneficial in the healing of injuries than in sporting enhancement. (11)

MEDICAL CONDITIONS


Growth hormone deficiency in patients with chronic heart failure and beneficial effects of its correction (2009)

Reduced activity of the GH/IGF-1 axis is well documented among patients with chronic heart failure (CHF), with as many as 40% of CHF patients being GH deficient. Furthermore, this subgroup of patients demonstrates higher mortality. Cittadini et al. sought to establish the clinical status of CHF patients with growth hormone deficiency (GHD), and re-evaluate this after a 6-month course of GH replacement therapy. At the end of the study, patients treated with GH had an improved overall quality of life, increased exercise duration, and increased oxygen uptake. Specific cardiovascular effects included reverse left ventricular (LV) remodelling, reduced LV systolic stress, and improved ventricular geometry. (12)


A preliminary study of growth hormone therapy for Crohn's disease (2000)

Inflammatory bowel disease (IBD) is characterised by immunological dysfunction and impaired epithelial repair. GH receptors are found throughout both the small and large bowel, where they play a role in the mediation of numerous biological functions, including epithelial proliferation. Slonim et al. studied the effects of subcutaneous GH in patients with moderate-to-severe Crohn’s disease. By the end of the study, the Crohn’s Disease Activity Index (CDAI) score had decreased by a mean of 143 point in the GH group, compared with a decrease of 19 points in the placebo group. Baseline scores were 287 and 213 in the GH and placebo groups respectively. (13)


A randomized, double-blind, placebo-controlled study of growth hormone in the treatment of fibromyalgia (1998)

The cause of fibromyalgia is unknown making it a challenging condition to treat. It is estimated that one third of fibromyalgia patients experience growth hormone deficiency, leading to undesirable symptoms such as decreased energy, impaired cognition, muscle weakness and poor general health. In this study, women with fibromyalgia and associated low IGF-1 levels were supplemented with daily subcutaneous injections of GH for a period of 9 months. When compared with placebo, GH resulted in an improvement in overall symptomatology and number of tender points. After discontinuing GH, patients experienced a worsening of symptoms. (14)

REFERENCES

  1. High WM, Jr., Briones-Galang M, Clark JA, Gilkison C, Mossberg KA, Zgaljardic DJ, et al. Effect of growth hormone replacement therapy on cognition after traumatic brain injury. Journal of neurotrauma. 2010 Sep;27(9):1565-75. PubMed PMID: 20578825. Pubmed Central PMCID: 2966848.

  2. Devesa J, Reimunde P, Devesa P, Barbera M, Arce V. Growth hormone (GH) and brain trauma. Hormones and behavior. 2013 Feb;63(2):331-44. PubMed PMID: 22405763.

  3. Doessing S, Heinemeier KM, Holm L, Mackey AL, Schjerling P, Rennie M, et al. Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis. The Journal of physiology. 2010 Jan 15;588(Pt 2):341-51. PubMed PMID: 19933753. Pubmed Central PMCID: 2821728.

  4. Menetrey J, Kasemkijwattana C, Day CS, Bosch P, Vogt M, Fu FH, et al. Growth factors improve muscle healing in vivo. The Journal of bone and joint surgery British volume. 2000 Jan;82(1):131-7. PubMed PMID: 10697329.

  5. Dunn AR. Intra-articular growth hormone injections regrow cartilage, increase motion and reduce pain in 93 per cent. of arthritic ankles. Osteoarthritis and Cartilage. 2012 April;20(S1):S295-S6.

  6. Bail H, Klein P, Kolbeck S, Krummrey G, Weiler A, Schmidmaier G, et al. Systemic application of growth hormone enhances the early healing phase of osteochondral defects--a preliminary study in micropigs. Bone. 2003 May;32(5):457-67. PubMed PMID: 12753861.

  7. Dunn AR. Morphoangiogenesis: a unique action of growth hormone. Microvascular research. 2002 May;63(3):295-303. PubMed PMID: 11969306.

  8. Raschke M, Kolbeck S, Bail H, Schmidmaier G, Flyvbjerg A, Lindner T, et al. Homologous growth hormone accelerates healing of segmental bone defects. Bone. 2001 Oct;29(4):368-73. PubMed PMID: 11595620.

  9. Raschke M, Rasmussen MH, Govender S, Segal D, Suntum M, Christiansen JS. Effects of growth hormone in patients with tibial fracture: a randomised, double-blind, placebo-controlled clinical trial. European journal of endocrinology / European Federation of Endocrine Societies. 2007 Mar;156(3):341-51. PubMed PMID: 17322494.

  10. Herndon DN, Tompkins RG. Support of the metabolic response to burn injury. Lancet. 2004 Jun 5;363(9424):1895-902. PubMed PMID: 15183630.

  11. Baumann GP. Growth hormone doping in sports: a critical review of use and detection strategies. Endocrine reviews. 2012 Apr;33(2):155-86. PubMed PMID: 22368183.

  12. Cittadini A, Saldamarco L, Marra AM, Arcopinto M, Carlomagno G, Imbriaco M, et al. Growth hormone deficiency in patients with chronic heart failure and beneficial effects of its correction. The Journal of clinical endocrinology and metabolism. 2009 Sep;94(9):3329-36. PubMed PMID: 19584187.

  13. Slonim AE, Bulone L, Damore MB, Goldberg T, Wingertzahn MA, McKinley MJ. A preliminary study of growth hormone therapy for Crohn's disease. The New England journal of medicine. 2000 Jun 1;342(22):1633-7. PubMed PMID: 10833209.

  14. Bennett RM, Clark SC, Walczyk J. A randomized, double-blind, placebo-controlled study of growth hormone in the treatment of fibromyalgia. The American journal of medicine. 1998 Mar;104(3):227-31. PubMed PMID: 9552084.

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