Human Growth Hormone and Athletic Performance
Part 1: Effect on Strength and Muscle Mass
By Dónal P. O’Mathúna, PhD
The use of human growth hormone (hgh) by athletes came to mass media attention with the arrest of several cyclists at the 1998 Tour de France.1 HGH is one of several peptide hormones banned by the International Olympic Committee and the National Collegiate Athletic Association, but laboratory examinations are not readily available to detect its use. Meanwhile, stories of extraordinary gains in strength and muscle mass circulate widely, and athletes of all abilities and ages—including adolescents—would love to have HGH’s purported beneficial effects. A 1992 study estimated that 5% of male students at U.S. high schools used or had used HGH.2
A huge marketing campaign has been launched to promote widespread use of HGH not for the treatment of disease, but for other reasons. Advertisements offer younger looks, increased energy, greater muscle strength, and long-lasting sexual vitality. They proclaim that thousands of scientific studies support their claims and conclude that "Anyone over 35 who wants to have good health and longevity will need to be on an HGH program."3 These claims relate to oral supplements alleged to stimulate endogenous hormone production, not subcutaneous HGH administration. Before your patients use HGH, the lack of tangible benefit and the serious side effects already seen in athletes must be examined carefully.
Background
Recombinant DNA technology has made available an abundant supply of HGH. Children and adults who naturally are deficient in HGH, and 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.4 People with acromegaly, a condition characterized by excessive endogenous HGH production, have larger, but not stronger, muscles.5
Pharmacology and Production
Growth hormone is a relatively small polypeptide secreted by the anterior pituitary gland in pulses several times a day.6 Normal HGH secretion is highest during slow-wave sleep. HGH production decreases dramatically after puberty. This decline underlies the 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 in concentration with age.
Endogenous production is intricately regulated by neural control, metabolic and hormonal feedback mechanisms, and circulating levels of various biochemicals.7 HGH production can be increased by exercise, stress, fever, fasting, and ingestion of amino acids like leucine and arginine.8 Particular drugs, like clonidine, L-dopa, gamma-hydroxybutarate (GHB), and corticosteroids, increase HGH production by acting directly on the pituitary.9 Secretion is reduced by hyperglycemia, obesity, and hypothyroidism.
Exercise increases HGH production dramatically. Prolonged moderate exercise can increase HGH levels 10-fold.8 Anaerobic, intense exercise can lead to a 100-fold increase in HGH production.10 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.
Mechanism of Action
HGH increases the uptake and incorporation of amino acids into muscle.6 HGH has acute, transient insulin-like effects that stimulate glucose uptake into muscle and adipose tissue.7 However, its chronic effects are antagonistic of insulin, leading to fatty acid mobilization, inhibition of glucose uptake, and reduced insulin sensitivity.8 HGH also has indirect effects mediated primarily by insulin-like growth factor-1 (IGF-1), although its mechanism of action is poorly understood.7
Clinical Studies
Controlled studies have not produced the huge gains reported anecdotally. An early double-blind, crossover study gave eight athletes methionyl-HGH for six weeks.11 Percent body fat decreased significantly, and fat-free mass (FFM) and serum IGF-1 increased significantly (P < 0.05). Muscle size and strength changes were not measured.
The first study to examine whether exogenous HGH administration potentiates the anabolic effects of resistance exercise involved 18 untrained men (average age 27 years).5 All subjects undertook 12 weeks of heavy resistance training, five days/week. The double-blind study randomly assigned subcutaneous injections of either saline or HGH given immediately after exercising. Subjects received 40 mcg/kg of HGH, equivalent to 2-4 times their daily secretion rate. Two HGH subjects withdrew because of carpal tunnel problems. FFM increased in both groups, with significantly greater increases in the HGH group (P < 0.01). Whole body protein synthesis rates increased more in the HGH group (P < 0.03) and total urinary nitrogen decreased more (P < 0.05). However, the fractional muscle protein synthesis rates did not change, suggesting that synthesis of proteins other than muscle was increased. The size and strength of all muscles measured increased, but with no differences between the two groups.
The same study design was used with 23 older sedentary men (average age 67 years).12 All exercised four days/week for 16 weeks and the HGH group received 12.5-24 mcg/kg. Five of the 13 HGH recipients were removed from the study because of carpal tunnel compression, arthralgia, and fluid retention in the hands and feet. The results mirrored those with the younger men, with no differences in muscle size, strength, or protein synthesis, while FFM increased more with HGH (P = 0.003).
The impact of HGH on seven experienced weight-lifting athletes was studied (average age 23 years).13 Each athlete continued his customary training schedule (3-6 days/week) and injected 40 mcg/kg/d HGH for 14 days. Fasting serum IGF-1 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 of HGH injected subcutaneously at bedtime.14 Three HGH subjects dropped out because of carpal tunnel compression and fluid retention in the hands. The HGH subjects had significantly greater increases in HGH (P < 0.01) and IGF-1 levels (P < 0.001). Other serum hormone and steroid levels did not change. Changes in FFM, lean body mass, and skeletal muscle strength were identical between the two groups.
Eighteen healthy men (ages 65-82 years) underwent 14 weeks of progressive weight training and then were randomized to receive either 20 mcg/kg/d HGH or placebo.15 They continued training for 10 more weeks. Muscle strength increased significantly in both groups during the initial 14 weeks (P = 0.0001), but not in the subsequent weeks. Body weight did not differ between groups, but the HGH group had a significantly greater increase in lean body mass and decrease in fat mass (P < 0.05). Needle biopsies of the vastus lateralis muscles revealed changes in the cross-sectional areas of type I and II muscle fibers during training, but with no differences between the two groups.16 No significant differences were found between the groups in levels of muscle HGH receptors, IGF-1, or mRNA expression of related genes. The authors concluded that HGH supplementation did not enhance the beneficial effects of exercise in older men.
Adverse Effects
In Yarasheski’s studies, 14 men and women withdrew because of carpal tunnel compression, arthralgia, and fluid retention in the hands and feet.17 Elsewhere, five of 11 HGH recipients experienced carpal tunnel and edema problems, with only two resolving spontaneously.14
Concerns about cardiac effects also have been raised with long-term supplementation of HGH. Fifteen body builders self-selected to take either anabolic steroids along with 0.15-0.30 IU/kg HGH, or to join a control group.18 After six weeks, the supplementing group had significantly lower high-density lipoprotein-cholesterol and apolipoprotein A-1 levels (P < 0.001), both of which are associated with higher risks of coronary disease. In acromegaly, sustained HGH excess is associated with cardiac pathology.19
Some countries still produce cadaveric HGH of questionable quality which may be available on the black market.20 In the early 1980s, several cases of Creutzfeldt-Jakob disease developed because of contaminated cadaveric HGH.
Chronic administration of HGH leads to insulin resistance,7 and after six weeks of HGH supple- mentation, five of seven subjects had suppressed endogenous HGH production.11 Increased morbidity and mortality has been observed in severely ill patients given HGH, but the reasons for this association were not established.21
Formulation and Dosage
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.8 Athletes sometimes cycle on and off HGH, and take lower doses along with anabolic steroids.
An athlete’s regimen can cost $2,000-$5,000 per month.9 Because of this expense, many of the advertisements for HGH as a dietary supplement actually promote amino acids that allegedly increase endogenous HGH production.8 These supplements most commonly contain arginine, ornithine, lysine, and tryptophan.
Conclusion
The favorable changes in body composition described can be explained by increased fluid retention, not increased muscle mass.12 Uncomfortable adverse effects occur frequently, which could 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. Exogenous HGH injections have produced none of the gains sought by athletes, and yet have many risks.
Clinical studies have not produced the types of muscle strength gains that are reported anecdotally. A limitation with these studies is that in practice, athletes often take larger, varying doses, and cycle on and off other anabolic agents. All or some of these agents may produce synergistic effects, but also are likely to put athletes at higher risk of adverse effects. Even if short-term gains occur, HGH is part of an intricate web of hormones and growth factors. Manipulating one part of this system most likely leads to counter-balancing changes in other metabolites. This increases the risk of unexpected adverse effects.
Recommendation
Use of HGH by athletes is banned by most sports organizations because of both ethical and medical concerns. Given the results of clinical trials, there is no clear benefit for athletes who inject HGH. In contrast, there are significant dangers, both medically and financially. Athletes considering this drug should be strongly urged to avoid its use completely.
Dr. O’Mathúna is Professor of Bioethics and Chemistry at Mount Carmel College of Nursing, Columbus, OH.
References
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2. Rickert VI, et al. Human growth hormone: A new substance of abuse among adolescents? Clin Pediatr 1992; 31:723-726.
3. Willix Jr., RD. Health care hoax. Advertisement.
4. Zachwieja JJ, Yarasheski KE. Does growth hormone therapy in conjunction with resistance exercise increase muscle force production and muscle mass in men and women aged 60 years or older? Phys Ther 1999;79:76-82.
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6. Roemmich JN, Rogol AD. Exercise and growth hormone: Does one affect the other? J Pediatr 1997; 131:S75-S80.
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10. Jenkins PJ. Growth hormone and exercise. Clin Endocrinol 1999;50:683-689.
11. Crist DM, et al. Body composition response to endogenous GH during training in highly conditioned adults. J Appl Physiol 1988;65:579-584.
12. Yarasheski KE, et al. Effect of growth hormone and resistance exercise on muscle growth and strength in older men. Am J Physiol 1995;268:E268-E276.
13. 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.
14. Deyssig R, et al. Effect of growth hormone treatment on hormonal parameters, body composition and strength in athletes. Acta Endocrinol 1993;128: 313-318.
15. Taaffe DR, et al. Effect of recombinant human growth hormone on the muscle strength response to resistance exercise in elderly men. J Clin Endocrinol Metab 1994;79:1361-1366.
16. Taaffe DR, et al. Lack of effect of recombinant human growth hormone (GH) on muscle morphology and GH-insulin-like growth factor expression in resistance-trained elderly men. J Clin Endocrinol Metab 1996; 81:421-425.
17. Yarasheski KE, Zachwieja JJ. Growth hormone therapy for the elderly: The fountain of youth proves toxic. JAMA 1993;270:1694.
18. 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.
19. Orme SM, et al. Mortality and cancer incidence in acromegaly: A retrospective cohort study. J Clin Endocrinol Metab 1998;83:2730-2734.
20. Deyssig R, Frisch H. Self-administration of cadaveric growth hormone in power athletes. Lancet 1993;341: 768-769.
21. Takala J, et al. Increased mortality associated with growth hormone treatment in critically ill adults. N Engl J Med 1999;341:785-792.
O'Mathuna DP. Human growth hormone and athletic performance. Part 1: Effect on strength and muscle mass. Altern Med Alert 2002;5:65-68.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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