March 21, 2008 — Growth hormone use increased lean body mass but not physical performance and was associated with adverse events, according to a systematic review in the March 18 Early Release issue of the Annals of Internal Medicine and will appear in the May 20 print issue of the Annals.

"Human growth hormone is reportedly used to enhance athletic performance, although its safety and efficacy for this purpose are poorly understood," write Hau Liu, MD, MBA, MPH, and colleagues from Santa Clara Valley Medical Center in San Jose, California; Stanford University in Stanford, California; and the Veterans Affairs Palo Alto Health Care System in Palo Alto, California. "This practice, often called sports doping, is banned by most professional sports leagues and associations, including the International Olympic Committee, Major League Baseball, and the National Football League. However, a wide range of athletes, including those from baseball, cycling, and track and field, have been implicated in or confessed to illicit growth hormone use."

The objective of this systematic review was to examine evidence concerning the effects of growth hormone on athletic performance in physically fit, young individuals. A search of MEDLINE, EMBASE, SPORTDiscus, and Cochrane Collaboration databases for English-language studies published between January 1966 and October 2007 identified randomized controlled trials comparing growth hormone treatment with no growth hormone treatment in community-dwelling healthy participants aged 13 to 45 years. Two authors independently reviewed the identified articles and abstracted data.

A total of 44 articles met inclusion criteria. These articles described 27 study samples in which a total of 303 participants received growth hormone, representing 13.3 person-years of treatment. Participants were young (mean age, 27 ± 3 years), lean (mean body mass index [BMI], 24 ± 2 kg/m²), and physically fit (maximum oxygen uptake, 51 ± 8 mL/kg of body weight per minute).

The identified studies varied in growth hormone dosage (mean, 36 ± 21 µg/kg per day) and treatment duration (mean, 20 ± 18 days) for studies giving growth hormone for more than 1 day. Compared with participants who did not receive growth hormone, those who did had increased lean body mass (mean increase, 2.1 kg; 95% confidence interval [CI], 1.3 - 2.9 kg), but strength and exercise capacity did not appear to improve.

In 2 of 3 studies that evaluated lactate levels during exercise, these were statistically significantly higher in growth hormone recipients. Soft tissue edema and fatigue were more frequently reported in growth hormone–treated participants vs those not treated with growth hormone.

Limitations of the review include few studies that evaluated athletic performance, and growth hormone protocols in the studies may not reflect real-world doses and regimens.

"Claims that growth hormone enhances physical performance are not supported by the scientific literature," the review authors write. "Although the limited available evidence suggests that growth hormone increases lean body mass, it may not improve strength; in addition, it may worsen exercise capacity and increase adverse events. More research is needed to conclusively determine the effects of growth hormone on athletic performance."

The Agency for Healthcare Research and Quality, the Department of Veteran Affairs, Stanford University Medical Center, Stanford University, Genentech, Inc, the National Science Foundation, and the Evidence-Based Medicine Center of Excellence of Pfizer supported this study. Some of the review authors have disclosed various financial relationships with Blue Cross and Blue Shield Association, Genentech, Teva, LG Life Sciences, Ambrx, and the US Attorney (expert testimony regarding off-label use of growth hormone).

Ann Intern Med. Published online March 18, 2008.

Clinical Context

Study Highlights

• The purpose of this systematic review was to determine the effects of growth hormone therapy on athletic performance in healthy, physically fit young adults.
• The primary goal was to assess the effects of growth hormone on body composition, strength, basal metabolism, and exercise capacity, and the secondary aim was to summarize evidence on adverse events associated with use of growth hormone in healthy, physically fit young adolescents and adults.
• The reviewers searched MEDLINE, EMBASE, SPORTDiscus, and Cochrane Collaboration databases for English-language studies published between January 1966 and October 2007.
• Inclusion criteria were randomized controlled trials comparing growth hormone treatment with no growth hormone treatment in community-dwelling, healthy participants aged 13 to 45 years.
• 2 authors independently reviewed the identified articles and abstracted data.
• 44 articles met inclusion criteria, describing 27 study samples in which a total of 303 participants received growth hormone, representing 13.3 person-years of treatment.
• Mean age of participants was 27 ± 3 years, and mean BMI was 24 ± 2 kg/m².
• Participants were physically fit, with mean maximal oxygen uptake of 51 ± 8 mL/kg of body weight per minute.
• The identified studies varied in growth hormone dosage (mean, 36 ± 21 µg/kg per day) and treatment duration (mean, 20 ± 18 days) for studies giving growth hormone for more than 1 day.
• Compared with participants who did not receive growth hormone, those who did had increased lean body mass (mean increase, 2.1 kg; 95% CI, 1.3 - 2.9 kg) and a near-significant trend toward decreased fat mass.
• Use of growth hormone had a minimal effect on key athletic performance outcomes such as gains in biceps and quadriceps strength and exercise capacity, and it may even be associated with worsened exercise capacity.
• Growth hormone therapy resulted in increased use of lipids for fuel during rest, reflected in a statistically significantly lower resting respiratory exchange ratio and respiratory quotient. However, this improvement did not appear to persist during exercise.
• In 2 of 3 studies that evaluated lactate levels during exercise, these were statistically significantly higher in growth hormone recipients. Increased lactate levels during exercise are associated with decreased exercise stamina and physical exhaustion.
• Soft tissue edema, joint pain, carpal tunnel syndrome, and fatigue were more frequently reported in growth hormone–treated participants vs those not treated with growth hormone. These adverse events may be related to fluid retention.
• Limitations of the review include few studies that evaluated athletic performance, growth hormone protocols in the studies may not reflect real-world doses and regimens, no studies evaluated growth hormone for periods longer than 3 months, and only a small percentage of participants were women.
• Based on these findings, the reviewers concluded that claims that growth hormone enhances physical performance are not supported by the scientific literature; limited available evidence suggests that growth hormone increases lean body mass, but it may not improve strength and may actually worsen exercise capacity and increase adverse events.
• The reviewers recommend more research to conclusively determine the effects of growth hormone on athletic performance.

Pearls for Practice

• A systematic review suggests that claims that growth hormone enhances physical performance are not supported by the scientific literature. Limited available evidence suggests that growth hormone increases lean body mass, but it may not improve strength and may actually worsen exercise capacity.
• In 2 of 3 studies that evaluated lactate levels during exercise, these were statistically significantly higher in growth hormone recipients. Soft tissue edema, joint pain, carpal tunnel syndrome, and fatigue were more frequently reported in growth hormone–treated participants vs those not treated with growth hormone. These adverse events may be related to fluid retention.

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