Human Growth Hormone for Improved Strength and Increased Muscle Mass in Athletes

By Dónal P. O'Mathúna, PhD, Dr. O'Mathúna is a lecturer in Health Care Ethics, School of Nursing, Dublin City University, Ireland; he reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.

On July 20, 2006, one of sport's superstars, Barry Bonds of the San Francisco Giants, breathed a sigh of relief.1 A federal grand jury failed to indict the star slugger. His trainer was then released from jail where he had been held in contempt of court for failing to testify against Bonds. Allegations of using performance-enhancing drugs have plagued Bonds' rise toward the career home run record, having surpassed Babe Ruth's mark in May 2006 and now lying second behind Hank Aaron. Various sources have claimed that Bonds has used human growth hormone (HGH) and steroids to boost his performance. Bonds has always denied the allegations.

Use of HGH by athletes has come to popular attention in recent years, especially with a number of high-profile arrests and banning of cyclists in the Tour de France.2 Besides anabolic steroids, the most commonly used performance-enhancing hormones are erythropoietin (EPO), insulin, and HGH.2 HGH is banned by the International Olympic Committee, the National Collegiate Athletic Association (NCAA), and all major sporting leagues. Tests for illicit use have serious limitations due to natural variability in HGH levels, normal daily fluctuation, and the need to test within 24 hours of injection. A new detection test was used at the 2004 Olympics in Athens and the 2006 Winter Olympics in Torino with no positive samples detected.3 Lack of detection is not believed to be due to lack of use. An NCAA study found that 3.5% of athletes had used HGH in the previous year, and a survey of 10th graders found that 5% were using HGH.4

Such use is based on stories of extraordinary gains in strength and muscle mass among serious athletes. These claims influence younger athletes who dream of competing at the highest level. At the same time, recreational athletes are exposed to advertisements that HGH will increase energy, build muscle strength, improve sex, and delay (if not prevent) aging.5 Advertisers allege that scientific studies support their claims and conclude, "Anyone over 35 who wants to have good health and longevity will need to be on an HGH program."6 Many of these claims relate to oral supplements that allegedly stimulate endogenous hormone production. More and more, however, physicians are being asked to provide the authentic material: prescriptions for injectable HGH. One-third of all HGH sales worldwide are estimated to be for unapproved uses.5 The evidence for and against its use by athletes will be reviewed here.

Background

Recombinant DNA technology has made available an abundant supply of HGH. Children and adults who are naturally deficient in HGH, and those who have the clinical syndrome of pituitary dwarfism, respond favorably to HGH replacement therapy. Such therapy increases growth, and is accompanied by anabolic effects including increased lean body mass and decreased fat mass.3

Pharmacology and Production

Growth hormone is a relatively small polypeptide secreted by the anterior pituitary gland in pulses several times a day.7 Normal HGH secretion is highest during slow-wave sleep. HGH production decreases dramatically after puberty. This decline underlies popular claims that HGH therapy will overcome aging—reminiscent of claims that the fountain of youth lies in supplements of various other hormones that decline with age.

Endogenous production is intricately regulated by neural control, metabolic and hormonal feedback mechanisms, and circulating levels of various biochemicals.8 HGH production can be increased by exercise, stress, fever, fasting, and ingestion of amino acids like leucine and arginine.9 Particular drugs, like clonidine, L-dopa, gamma-hydroxybutyrate (GHB), and corticosteroids, increase HGH production by acting directly on the pituitary. Secretion is reduced by hyperglycemia, obesity, and hypothyroidism.

Exercise increases HGH production dramatically. Prolonged moderate exercise can increase HGH levels 10-fold.9 Anaerobic, intense exercise can naturally lead to extremely high HGH concentrations in some non-doping athletes.2 With intense exercise, peak production usually is attained 15-30 minutes after exercise is completed. To mimic this, athletes usually inject HGH shortly after training. Elevated levels return to baseline 8-16 hours after intramuscular injection and 11-20 hours after subcutaneous injection.3 This contributes to the difficulty of identifying athletes who are doping.

Mechanism of Action

HGH binds to specific membrane receptors and binding proteins throughout the body.8 The hormone increases the uptake and incorporation of amino acids into muscle.7 HGH has acute, transient insulin-like effects that stimulate glucose uptake into muscle and adipose tissue.8 However, its chronic effects are antagonistic of insulin, leading to fatty acid mobilization, inhibition of glucose uptake, and reduced insulin sensitivity.9 HGH also has indirect effects mediated primarily by insulin-like growth factor-I (IGF-I) produced by the liver, although its mechanism of action is poorly understood.8

Clinical Studies

The results of controlled studies differ greatly from anecdotal reports from underground users. Such use often involves several anabolic drugs at very high doses and in complex regimens specific to each sport. Controlled studies are few and usually involve HGH alone at lower doses. Therefore, the effectiveness and safety of HGH usage is difficult to evaluate.

A prior review in this publication included five studies with untrained men.10 These found that HGH administration produced physiological changes, but muscle mass and strength did not change significantly compared to control groups.

An early study with athletes enrolled seven experienced weight-lifters (average age 23 years).11 Each athlete continued his customary training schedule (3-6 days/week) and injected 40 mcg/kg/d HGH for 14 days. Fasting serum IGF-I levels doubled (P = 0.002). The rate of skeletal muscle protein synthesis did not change significantly during the trial, nor did whole body protein breakdown, suggesting no ergogenic benefit from HGH supplementation.

Twenty-two male power athletes (average age 23 years) were randomly assigned to either placebo or 0.09 U/kg/d injected subcutaneously at bedtime.12 Three HGH subjects dropped out because of carpal tunnel compression and/or fluid retention in the hands. The HGH subjects had significantly greater increases in HGH (P < 0.01) and IGF-I levels (P < 0.001). Other serum hormone and steroid levels did not change. Changes in fat-free mass, lean body mass, and skeletal muscle strength were identical between the two groups.

Eleven male endurance athletes (average age 32 years) were randomized to either placebo or 0.067 mg/kg HGH injected subcutaneously at bedtime.13 Radio-labeled leucine (an amino acid) was infused into the athletes to provide three different methods of measuring protein metabolism. HGH administration led to a significantly greater anabolic effect among athletes both at rest (P < 0.01) and during or after exercise (P < 0.05). The increase was visible after one week of HGH injections and accentuated after four weeks. The placebo group did not change compared to baseline.

Thirty healthy active subjects, none of whom were professional athletes, took part in the most recent controlled study.14 An equal number of men and women participated. All were randomly assigned to receive either HGH 0.033 mg/kg, HGH 0.067 mg/kg, or placebo daily for 28 days. Exercise measurements were made before and after the 28 days using a bicycle ergometer with automatic load increase. The maximum power output and maximum oxygen uptake did not vary significantly between the three groups. No significant differences were found for muscle mass, heart rate, blood pressure, or ECG readings. Total body weight was significantly higher for the higher HGH dose compared to placebo (P = 0.028), with calculations showing that this was primarily due to increased water retention.

Adverse Effects

Acromegaly is a syndrome in which people produce higher than normal levels of HGH.13 People with this condition have abnormal protein remodeling in skeletal muscle and other organs. While muscle mass is increased, physical strength and endurance are reduced. Concerns have been raised that sustained elevated HGH from exogenous sources will lead to similar problems.

Acromegaly is also associated with cardiac pathology.15 In one small study, 15 body builders were self-selected to take either testosterone and anabolic steroids along with 0.15-0.30 IU/kg HGH, to take HGH alone, or to join a control group.16 After six weeks, the supplementing group had significantly lower HDL-cholesterol and apolipoprotein A-1 levels (P < 0.001), both of which are associated with higher risks of coronary disease.

Carpal tunnel compression, arthralgias, and fluid retention are common complaints in controlled studies.17 Chronic administration of HGH can lead to insulin resistance and suppression of endogenous HGH production.2 Increased morbidity and mortality has been observed in severely ill patients given HGH, but the reasons for this association were unclear.18 Other serious adverse effects have occurred because cadaveric HGH of questionable quality has been available on the black market.19 In the early 1980s, several cases of Creutzfeldt-Jakob disease developed because of contaminated cadaveric HGH.

Formulation

HGH-deficient adults usually take 1-2 IU/d by subcutaneous injection every evening. Athletes sometimes take as much as 10-25 IU/d, three or four times a week.3 It is often taken in 4-6 week cycles and in combination with other performance-enhancing agents, especially anabolic steroids. An athlete's regimen can cost about $5,000 per month.4 Because of this cost, many HGH advertisements actually promote supplements containing amino acids, most commonly arginine, ornithine, lysine, and tryptophan.3 These allegedly increase endogenous HGH production.

Conclusion

The most recent randomized controlled trial with athletes concluded that HGH administration has demonstrated no beneficial effects and that only untoward effects can be expected.14 A limitation with such studies is that in practice athletes often take larger, varying doses, and cycle on and off HGH and other anabolic agents. All or some of these may have synergistic effects, but are also likely to put athletes at greater risk. In addition, HGH is part of an intricate web of natural hormones and growth factors. Manipulating one part of the system will lead to counter-balancing changes in other metabolites, thus increasing the risk of unexpected adverse effects.

The favorable changes in body composition described anecdotally can be explained by increased fluid retention.14 Such changes can be enough to lead athletes to believe they can compete better which may in fact improve actual performance. However, water retention and other adverse effects can interfere with athletic performance. More serious adverse effects also can occur. Particular concerns exist about the quality of HGH available on the black market, especially given the hormone's expense.

Recommendation

Use of HGH by athletes is banned by most sports organizations because of both ethical and medical concerns. Clinical trials with exogenous HGH injections have produced none of the gains sought by athletes, and point to many risks. Athletes, whether serious or recreational, who are considering this drug should be strongly urged to avoid its use completely.

References

1. Associated Press. No indictment for Bonds. SI.com. Available at: http://sportsillustrated.cnn.com/2006/baseball/mlb/07/20/grandjury.thursday.ap/index.html?section=cnn_us. Accessed June 26, 2006.

2. Minuto F, et al. Indirect evidence of hormone abuse. Proof of doping? J Endocrinol Invest 2003;26:919-923.

3. Saugy M, et al. Human growth hormone doping in sport. Br J Sports Med 2006;40(suppl 1):i35-i39.

4. Calfee R, Fadale P. Popular ergogenic drugs and supplements in young athletes. Pediatrics 2006;117:e577-e589.

5. Newman J. The supernatural. Vogue August 2006:288-300.

6. Willix, Jr., RD. Health care hoax. Advertisement received in the mail.

7. Roemmich JN, Rogol AD. Exercise and growth hormone: Does one affect the other? J Pediatr 1997;131(1 Part 2):S75-S80.

8. Yarasheski KE. Growth hormone effects on metabolism, body composition, muscle mass, and strength. Exerc Sport Sci Rev 1994;22:285-312.

9. Ehrnborg C, et al. Growth hormone abuse. Baillieres Best Pract Res Clin Endocrinol Metab 2000;14:71-77.

10. O'Mathúna DP. Human growth hormone and athletic performance. Part 1: Effect on strength and muscle mass. Altern Med Alert 2002;5:65-68.

11. Yarasheski KE, et al. Short-term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters. J Appl Physiol 1993;74:3073-3076.

12. Deyssig R, et al. Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Acta Endocrinol (Copenh) 1993;128:313-318.

13. Healy ML, et al. High dose growth hormone exerts an anabolic effect at rest and during exercise in endurance-trained athletes. J Clin Endocrinol Metab 2003;88:5221-5226.

14. Berggren A, et al. Short-term administration of supraphysiological recombinant human growth hormone (GH) does not increase maximum endurance exercise capacity in healthy, active young men and women with normal GH-insulin-like growth factor I axes. J Clin Endocrinol Metab 2005;90:3268-3273. Epub 2005 March 22.

15. Orme SM, et al. Mortality and cancer incidence in acromegaly: A retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab 1998;83:2730-2734.

16. Zuliani U, et al. Effects of anabolic steroids, testosterone, and HGH on blood lipids and echocardiographic parameters in body builders. Int J Sports Med 1989;10:62-66.

17. Yarasheski KE, Zachwieja JJ. Growth hormone therapy for the elderly: The fountain of youth proves toxic. JAMA 1993;270:1694.

18. Takala J, et al. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 1999;341:785-792.

19. Deyssig R, Frisch H. Self-administration of cadaveric growth hormone in power athletes. Lancet 1993;341:768-769.