Growth Hormone and Sports

Andrew R. Hoffman, MD

Department of Medicine

Stanford University School of Medicine

Stanford, CA

Why is GH Popular in the Doping World?

• GH is on the list of banned substances, so it must be effective.

• It’s called “growth hormone,” so it must really be anabolic.

• It is difficult to detect illicit use of GH.

• GH levels increase during exercise.

• Lipolytic and water retaining properties are readily apparent, suggesting that GH is “working.”

• There are well documented anabolic effects and improvement in exercise capabilities in patients with GH-deficiency syndrome.

• GH is said to promote faster recovery to allow the athlete to train more and train harder.

• GH is reputed to prevent tendon and muscle injuries induced by anabolic steroids, so it can be given in conjunction with other anabolic agents.

• Scientific studies are of short duration and the doses of GH that the scientists use do not represent doses used by athletes, so GH really has never been properly tested.

Ehrnborg and Rosen, GH & IGF Res, 2009Rogel, GH& IGF Res, 2009

What the Athletes Know

Ironman Magazine, 2007 Popular “Myths” about GH

• GH enables you to eat as many as 10,000 calories a day yet lose appreciable levels of body fat simultaneously

• GH promotes hyperplasia, or a splitting of muscle fibers into new fibers—a property that other anabolic hormones don’t have

• GH provided little or no actual anabolic or muscle-building effects by itself but did pack a punch when used with anabolic steroids.

• When the steroids were eliminated a few weeks before the contest, GH froze the muscle size produced by the earlier drug cycles and kept delivering fat-loss benefits

Report to the Commissioner of Baseball of an Independent

Investigation into the Illegal Use of Steroids and Other Performance

Enhancing Substances by Players in Major League Baseball (2007)

GEORGE J. MITCHELL

A number of studies have shown that use of human growth hormone does not increase muscle strength in healthy subjects or well-trained athletes. Athletes who have tried human growth hormone as a training aid have reached the same conclusion. The author of one book targeted at steroid abusers observed that

“[t]he most curious aspect of the whole situation is that I’ve never encountered any athlete using HGH to benefit from it, and all the athletes who admit to having used it will usually agree: it didn’t/doesn’t work for them.”

Effect of GH replacement on muscle strength in patients with GH-deficiency: a meta-analysis

• Long term (up to 10+ years) observational studies suggest that GH replacement leads to increased strength

• 8 studies with utilizable, robust data, involving 231 patients in 9 cohorts

• Randomized, double-blind, placebo-controlled, of parallel or cross-over design and of an average 6·7 months duration

Widdowson and Gibney, Clin Endo 2010

Results: No significant improvement in muscle strength

GH replacement therapy in adults with GH deficiencyExercise

Hartman et al. JCEM 2008; 93:125-130

Effect of GH Replacement on Exercise Capacity in Patients

with GH Deficiency: A Meta-analysis

• 11 randomized, double blind, placebo controlled studies, either parallel or crossover design, involving a total of268 patients.

• 6-18 months of GH therapy

• GH replacement was associated with significant improvement with all studies combined for maximal power output and maximal oxygen uptake

Benefit of GH replacement expressed as percent change from baseline compared with placebo-combined variable

Widdowson and Gibney, JCEM 2008

Effect of growth hormone and resistance exerciseon muscle growth in young men

Yaresheski et al Am J Physiol, 1992

• Protocol

18 young men (21-34 yr) assigned to heavy resistance training ± GH

GH dose: 40 mcg/kg/d for 12 weeks

Two GH-treated men developed carpal tunnel syndrome and left protocol

• In comparison to placebo controls, GH-treated men had

Increase in fat free mass

Increase in total body protein synthesis

But no change in

muscle protein synthesis

muscle size

strength

GH and Exercise in the Elderly

• 18 healthy elderly men (65-82 yr) underwent progressive resistance training for 14 weeks and were then randomized to either GH (0.02 mg/kg/d) or placebo while undertaking a further 10 weeks of training.

• Vastus lateralis samples were obtained at baseline and at 14 and 24 weeks.

Taafe et al. JCEM 1996

• GH did not enhance strength

• No change in muscle GH receptor, IGF-I, IGF-I receptor, IGF-II, or IGF-II receptor mRNAs as a result of exercise or after treatment with GH or placebo.

• GH did not alter type I or type II fiber area

Meta-Analysis of the Effect of GH on Athletic Performance

Liu H et al. Ann Intern Med 2008;148:747-758

October 2007

27 unique study samples

303 subjects received GH13.3 person-years of treatment

Effect of GH on basal metabolism.

Liu H et al. Ann Intern Med 2008;148:747-758©2008 by American College of Physicians

BMR

RER or RQ

HeartRate

Effect GH on body composition

Liu H et al. Ann Intern Med 2008;148:747-758

Weight

Fat Mass

Lean BodyMass

Effect of GH on strength

Liu H et al. Ann Intern Med 2008;148:747-758

Key Adverse Events.

Liu H et al. Ann Intern Med 2008;148:747-758

©2008 by American College of Physicians

Limitations of the Systematic Analysis

• Very few high quality trials have been performed.

• Few studies evaluated athletic performance. Through 2007, only 8 studies assessed strength or exercise capacity in a randomized manner.

• The dose of GH varied in these studies, and none of the doses approximated the dosing by athletes.

• No studies evaluated the use of GH for >3 months.

• Almost no data on the effect of GH on women athletes.

• The subject populations are varied, ranging from "highly trained" to "untrained.”

Short-Term rhGH Administration in Abstinent Steroid Dependent Men

• 48 men (average age 32), abstinent from drug use for at least 12 weeks, treated with GH 19 mcg/kg/d for 6 days.

• Single-blind randomized control trial

Graham et al Horm Res 2008

Short-Term rhGH Administration in Abstinent Steroid Dependent Men

• Decreased anxiety and decreased depressive symptoms after 6 days of GH.

• Improved psychologic parameters persisted for one week after cessation of GH

“The self-administration of rhGH by the intelligent athlete, may prevent any chinks in the psychological armour, in preparation for stressful combat and so improve psychological performance pre-contest and provide an edge over competitors.”

Graham et al Horm Res 2008; GH& IGF Res, 2009; Curr Neurovasc Res, 2007

GH + Testosterone Effect on Muscle Performance in Older Men

• 122 community-dwelling men aged 65-90 (mean age 70.4 yr)

IGF-I level in lower adult tertile (≤167 ng/dl)

Testosterone level in lower half of population (≤ 550 ng/dl)

• Treatment period of 16 weeks

All men received transdermal T (5g/d or 10g/d)

Men received rhGH (0, 3 or 5 mcg/kg/d)

Sattler, F. R. et al. J Clin Endocrinol Metab 2009;94:1991-2001

Copyright ©2009 The Endocrine Society

Sattler, F. R. et al. J Clin Endocrinol Metab 2009;94:1991-2001

Changes in serum testosterone (A) and IGF-I (B) from baseline to wk 16 according to dose

Copyright ©2009 The Endocrine Society

Sattler, F. R. et al. J Clin Endocrinol Metab 2009;94:1991-2001

DEXA-derived changes in LBM and fat mass for each treatment group from baseline to wk 17

Total Appendicular

Total Trunk

TABLE 3. Change in composite maximum voluntary strength and aerobic endurance

Sattler, F. R. et al. J Clin Endocrinol Metab 2009;94:1991-2001

The effects of GH on body composition and physical performance

in recreational athletes: a randomized trial.

• OBJECTIVE: To determine the effect of growth hormone alone or with testosterone on body composition and measures of performance.

• PARTICIPANTS: 96 recreationally trained athletes (63 men and 33 women) with a mean age of 27.9

• INTERVENTION:

Men were randomly assigned to receive placebo, growth hormone (2 mg/d subcutaneously), testosterone (250 mg/wk intramuscularly), or combined treatments.

Women were randomly assigned to receive either placebo or growth hormone (2 mg/d).

• PRIMARY FUNDING SOURCE: The World Anti-Doping Agency.

Meinhardt U et al. Ann Intern Med 2010;152:568-577

The effects of GH on body composition and physical performance

in recreational athletes: a randomized trial.

Results

• Body cell mass was correlated with all measures of performance at baseline.

• Growth hormone significantly reduced fat mass, increased lean body mass through an increase in extracellular water, and increased body cell mass in men when co-administered with testosterone.

• Growth hormone significantly increased sprint capacity (anaerobic work capacity), by 0.71 kJ (relative increase, 3.9%) in men and women combined and by 1.7 kJ (relative increase, 8.3%) when co-administered with testosterone in men

• Other performance measures did not significantly change.

• The increase in sprint capacity was not maintained 6 weeks after discontinuation of the drug.

Percentage change in body composition variables.Data are expressed as means (95% CIs).

Meinhardt U et al. Ann Intern Med 2010;152:568-577

©2010 by American College of Physicians

Percentage change in performance variables.Data are expressed as means (95% CIs).

Meinhardt U et al. Ann Intern Med 2010;152:568-577

©2010 by American College of Physicians

Summary

• Claims that GH increases strength and improves athletic performance are not based on a robust body of scientific evidence. Large changes are rarely reported.

• GH may increase total lean body mass, but there is little evidence that it increases muscle mass in normal individuals.

• GH may enhance the effect of androgens to increase strength and performance.

• Large doses of GH will causes serious side effects, even in young healthy individuals.

A Lesson from the Androgen Story

In summary, neither enhancement of weight nor improvement in strength can be demonstrated consistently when androgens are administered double blind to athletes. Most reviewers in the field have consequently concluded that a positive relationship between androgen use and athletic performance is unproven and that effects on weight and muscle mass are inconsistent. Admittedly, the total number of athletes studied carefully is small, and it is possible that androgens work in some individuals but not others and that if the individual groups had been larger, negative results might have become positive; alternatively, positive results might have disappeared.

Androgen Abuse by Athletes

JEAN D. WILSON

Endocrine Reviews, 1988

600 mg of testosterone enanthate or placebo weekly for 10 weeks

Bhasin S et al. N Engl J Med 1996;335:1-7.

Barriers to Real-Life Testing of GH as an Ergogenic Aid

• Problems with dosing

Need to use doses of GH similar to those used by athletes

Need to use high doses of other anabolic agents in conjunction with GH

With high doses of GH or steroids, blinding will be difficult

• Problems with study design

Long term trials (at least 3 months?) may be required

Changes with GH likely to be relatively small, requiring a large n

• Feasibility

GH is very expensive

Pharmaceutical companies not interested in sponsoring these trials

• Institutional review boards and ethical considerations