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The Effects of Growth Hormone on Body Composition and Physical Performance in Recreational Athletes: A Randomized Trial

Udo Meinhardt, MD; Anne E. Nelson, PhD; Jennifer L. Hansen, RN; Vita Birzniece, MD, PhD; David Clifford, PhD; Kin-Chuen Leung, PhD; Kenneth Graham, BSc; and Ken K.Y. Ho, MD
[+] Article and Author Information

From Garvan Institute of Medical Research and St Vincent's Hospital, Darlinghurst; St. Vincent's Clinical School, University of New South Wales; CSIRO Mathematical and Information Sciences, North Ryde; and New South Wales Institute of Sports, Sydney, New South Wales, Australia.


Note: Drs. Meinhardt and Nelson contributed equally to this article.

Acknowledgment: The authors thank Professor Robert Baxter, Professor David Handlesman, and Dr. Ray Kazlauskas for their contribution to the larger project that this study was part of. They also thank Dr. Glenn Stone for statistical advice; Sue Min Choong and Amie Lau for technical support; Irene Walker and Angela Peris for clinical assistance; all the volunteers for their participation; and the University of New South Wales (UniGym, Sports Association, and the Faculties of Sports Science and Medicine), University of Sydney (Sydney University Sport and the Faculty of Medicine), and the Australian College of Physical Education for assistance with recruitment.

Grant Support: By the World Anti-Doping Agency, Australian Government (through the Anti-Doping Research Program of the Department of Communications, Information Technology, and the Arts), and the Swiss National Foundation and the Federal Council of Sports (Dr. Meinhardt). Novo Nordisk and Organon provided the study medication.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M09-0826.

Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Ho (K.ho@garvan.org.au).

Requests for Single Reprints: Ken K.Y. Ho, MD, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Sydney, Australia; e-mail, k.ho@garvan.org.au.

Current Author Addresses: Dr. Meinhardt: Centre for Pediatric Endocrinology, Moerlistrasse 69, CH 8006 Zurich, Switzerland.

Drs. Nelson, Birzniece, and Ho and Ms. Hansen: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Sydney, Australia.

Dr. Clifford: CSIRO Mathematical and Information Sciences, North Ryde, New South Wales 1670, Sydney, Australia.

Dr Leung: Department of Infectious Diseases and Microbiology, The Children's Hospital at Westmead, New South Wales 2145, Westmead, Australia.

Mr. Graham: New South Wales Institute of Sports, Olympic Park, New South Wales 2127, Sydney, Australia.

Author Contributions: Conception and design: U. Meinhardt, A.E. Nelson, K.C. Leung, K. Graham, K.K.Y. Ho.

Analysis and interpretation of the data: U. Meinhardt, A.E. Nelson, J.L. Hansen, V. Birzniece, D. Clifford, K.C. Leung, K. Graham, K.K.Y. Ho.

Drafting of the article: U. Meinhardt, A.E. Nelson, J.L. Hansen, V. Birzniece, K.C. Leung, K. Graham, K.K.Y. Ho.

Critical revision of the article for important intellectual content: U. Meinhardt, A.E. Nelson, V. Birzniece, K.C. Leung, K. Graham, K.K.Y. Ho.

Final approval of the article: U. Meinhardt, A.E. Nelson, V. Birzniece, D. Clifford, K.C. Leung, K. Graham, K.K.Y. Ho.

Provision of study materials or patients: U. Meinhardt, K. Graham.

Statistical expertise: D. Clifford, K.K.Y. Ho.

Obtaining of funding: A.E. Nelson, K.C. Leung, K.K.Y. Ho.

Administrative, technical, or logistic support: U. Meinhardt, A.E. Nelson, K.K.Y. Ho.

Collection and assembly of data: U. Meinhardt, A.E. Nelson, J.L. Hansen, V. Birzniece.


Ann Intern Med. 2010;152(9):568-577. doi:10.7326/0003-4819-152-9-201005040-00007
Text Size: A A A

Background: Growth hormone is widely abused by athletes, frequently with androgenic steroids. Its effects on performance are unclear.

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

Design: Randomized, placebo-controlled, blinded study of 8 weeks of treatment followed by a 6-week washout period. Randomization was computer-generated with concealed allocation. (Australian–New Zealand Clinical Trials Registry registration number: ACTRN012605000508673)

Setting: Clinical research facility in Sydney, Australia.

Participants: 96 recreationally trained athletes (63 men and 33 women) with a mean age of 27.9 years (SD, 5.7).

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).

Measurements: Body composition variables (fat mass, lean body mass, extracellular water mass, and body cell mass) and physical performance variables (endurance [maximum oxygen consumption], strength [dead lift], power [jump height], and sprint capacity [Wingate value]).

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 coadministered with testosterone. Growth hormone significantly increased sprint capacity, by 0.71 kJ (95% CI, 0.1 to 1.3 kJ; relative increase, 3.9% [CI, 0.0% to 7.7%]) in men and women combined and by 1.7 kJ (CI, 0.5 to 3.0 kJ; relative increase, 8.3% [CI, 3.0% to 13.6%]) when coadministered with testosterone to men; other performance measures did not significantly change. The increase in sprint capacity was not maintained 6 weeks after discontinuation of the drug.

Limitations: Growth hormone dosage may have been lower than that used covertly by competitive athletes. The athletic significance of the observed improvements in sprint capacity is unclear, and the study was too small to draw conclusions about safety.

Conclusion: Growth hormone supplementation influenced body composition and increased sprint capacity when administered alone and in combination with testosterone.

Primary Funding Source: The World Anti-Doping Agency.

Figures

Grahic Jump Location
Appendix Figure 1.
Percentage change in body composition variables.

Data are expressed as means (95% CIs).

Grahic Jump Location
Grahic Jump Location
Appendix Figure 2.
Percentage change in performance variables.

Data are expressed as means (95% CIs). V̇o2max = maximum oxygen consumption.

Grahic Jump Location
Grahic Jump Location
Appendix Figure 3.
Baseline relationships in women and men.

The regression lines and their corresponding equation are shown. BCM = body cell mass; V̇o2max = maximum oxygen consumption.

Grahic Jump Location

Tables

References

Letters

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Comments

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Misleading Interpretations and Public Misinformation: The Impact of One Poorly Chosen Sentence
Posted on May 5, 2010
Shawn C. Sorenson
University of Southern California - Division of Biokinesiology and Physical Therapy
Conflict of Interest: None Declared

The article by Meinhardt et al. titled "The Effects of Growth Hormone on Body Composition and Physical Performance in Recreational Athletes" is important and informative. This randomized, controlled trial evaluating the independent and synergistic effects of exogenous growth hormone (GH) and testosterone (T) on selected physiologic and athletic performance measures is a valuable contribution to the scientific literature. It also provides critical evidence to the ongoing social and scientific debate surrounding sports doping.

The study demonstrates significant increases in anaerobic work capacity, as measured by the Wingate cycle test, following 8 weeks of treatment with GH, with and without concurrent T administration. While effect sizes were modest (0.22-0.38 for GH alone, and 0.61 for GH & T), these findings suggest a previously unreported physiological effect that has potential implications toward athletic performance. The authors correctly conclude, however, that the athletic significance of these findings is uncertain.

Unfortunately, oversights in the presentation of this study have led to erroneous interpretations in mainstream media that compromise the impact of this important work, and carry dangerous ramifications, especially when viewed by an untrained audience.

The characterization of anaerobic work capacity as "sprint capacity" is inaccurate and misleading. Though equivocal support exists for cycle ergometry as a significant predictor of sprint running performance (3,6), it is widely recognized that additional factors including strength and power are important determinants (1,5). To suggest even semantically that Wingate test performance and the capacity to sprint are equivalent measures is wrong.

More egregiously, even while acknowledging such limitations, the authors go on to speculate in specific terms how their findings among recreational athletes translate to 100m running and 50m swimming times in world-class competitors:

"We do not know how an improvement in Wingate test performance translates to performance in the sporting field, but we speculate that the approximately 4% increase in sprint capacity that we observed could translate to an improvement of 0.4 second in a 10-second sprint over 100 meters or of 1.2 seconds in a 30-second swim over 50 meters."

This unsubstantiated claim is made without basis, evidence, or even compelling explanation. Nonetheless, it forms the featured conclusion of numerous prominent media reports, including this from the Los Angeles Times:

"Injections of human growth hormone can improve sprint capacity enough to turn the last-place finisher in the Olympic 100-meter dash into a gold-medal winner, according to a study released Monday (4)."

Disturbingly, at least one study author appears to have expressly endorsed this interpretation.

"Dr Ken Ho, who led the study, said: 'This improvement could turn the last place finisher in the Olympic finals into a gold medal winner' (2)."

Such gross mischaracterization of the study findings is possible only because authors, reviewers, and editors alike failed to screen this language from the manuscript. While some may view this as a victory in the highly publicized battle against sports doping, it is scientifically inaccurate, unethical, and irresponsible. Ironically, it also has the potential to encourage the abuse of doping agents by exaggerating their efficacy.

As scientists we have a responsibility to present facts and interpretations to colleagues and lay audiences alike in a manner that promotes truth and understanding. We are obliged to objectively express in context not only our findings, but also our limitations and biases. It is regrettable that our community has missed such a key opportunity to do so.

References

1. Cronin, J.B., & Hansen, K.T. (2005). Strength and power predictors of sports speed. Journal of Strength and Conditioning Research, 19(2), 349-357.

2. Hutchison, P. (2010, May 4). Human growth hormone 'makes worst athlete the best'. The Daily Telegraph. Retrieved from http://www.telegraph.co.uk

3. Meckel, Y., Atterbom, H., Grodjinovsky, A., Ben-Sira, D., & Rotstein, A. (1995). Physiological characteristics of female 100 metre sprinters of different performance levels. The Journal of Sports Medicine and Physical Fitness, 35(3), 169-75.

4. Roan, S. (2010, May 3). Study shows growth hormone boosts sprint speed. The Los Angeles Times. Retrieved from http://www.latimes.com

5. Smirniotou, A., Katsikas, C., Paradisis, G., Argeitaki, P., Zacharogiannis, E., & Tziortzis, S. (2008). Strength-power parameters as predictors of sprinting performance. The Journal of Sports Medicine and Physical Fitness, 48(4), 447-54.

6. Zagatto, A.M., Beck, W.R., & Gobatto, C.A. (2009). Validity of the running anaerobic sprint test for assessing anaerobic power and predicting short-distance performances. Journal of Strength and Conditioning Research, 23(6), 1820-1827.

Conflict of Interest:

None declared

Re:Misleading Interpretations and Public Misinformation: The Impact of One Poorly Chosen Sentence
Posted on May 12, 2010
Ken K.Y. Ho
Pituitary Research Unit, Garvan Institute of Medical Research
Conflict of Interest: None Declared

Mr. Sorensen has voiced concerns at the interpretation and media communication of our findings centred on a sentence in the Discussion of our paper.

There is objection to an apparent characterization of anaerobic work capacity as 'sprint capacity', and to an apparent claim that Wingate test performance and capacity to sprint are 'equivalent measures'.

Wingate test performance depends on all available forms of muscle energy supply and is primarily a measure of power and anaerobic capacity (1). In the context of broad performance categories assessed in our study, it is the form of testing that is most closely aligned to sprint events (not endurance running, weight lifting or high jump). We did not state that Wingate test and the capacity to sprint are 'equivalent measures'. While strength and power are determinants of sprint capacity (2), we found no evidence that either was enhanced by GH, leading us to postulate that the anaerobic energy required to drive contractile muscle function may be increased by GH. Indeed several studies have demonstrated a positive relationship between Wingate anaerobic capacity and sprint performance (3-5).

Our speculation as to what an improvement in Wingate performance might mean in a sprint event is based on mechanistic and conceptual deduction. To cast this as an unsubstantiated claim appears to be a misreading of a considered extrapolation that has passed the most stringent standards of expert review.

We agree that challenges remain in bridging the gulf between scientific findings and media communication. Selected and simplified information in a compressed media platform can distort as the reaction to one selected sentence can.

References

1. Green S. Measurement of anaerobic work capacities in humans. Sports Med. 1995 Jan;19(1):32-42.

2. Cronin JB, Hansen KT. Strength and power predictors of sports speed. J Strength Cond Res. 2005 May;19(2):349-57.

3. Meckel Y, Atterbom H, Grodjinovsky A, Ben-Sira D, Rotstein A. Physiological characteristics of female 100 metre sprinters of different performance levels. J Sports Med Phys Fitness. 1995 Sep;35(3):169-75.

4. Meckel Y, Machnai O, Eliakim A. Relationship among repeated sprint tests, aerobic fitness, and anaerobic fitness in elite adolescent soccer players. J Strength Cond Res. 2009 Jan;23(1):163-9.

5. Patton JF, Duggan A. An evaluation of tests of anaerobic power. Aviat Space Environ Med. 1987 Mar;58(3):237-42.

Growth hormone: Fishing for a "performance effect" on the media?
Posted on May 31, 2010
Ehlert Tobias
Department of Sports Medicine, Rehabilitation and Disease Prevention, Johannes Gutenberg-University
Conflict of Interest: None Declared

Meinhardt and colleagues reported in their study "The Effects of Growth hormone on body Composition and Physical Performance in Recreational Athletes" significant water retention and reduction of fat mass, while endurance, strength, power and muscle mass was not significantly altered following GH administration. These findings are in line with previous studies (1; 2). Meinhardt and co-workers are the first to suggest an effect of GH in a Wingate test procedure. Experts in exercise physiology are critically discussing the athletic significance of the Wingate test (3), while the authors speculate in the article and in a video message addressed to the mass media that this could translate into an improvement of 0.4 second in a 10-second sprint over 100m. Given the study collective, a more rational speculation could have been that a recreational athlete might be able to improve the 100m sprint time by about half a second. Therefore we should have a closer look at the precise scientific findings of this study and their potential significance for the field of exercise physiology. The authors clearly state that this is an analysis of secondary outcome data. Accordingly, it is not surprising that "training quantity" as an important factor influencing performance outcome measurements is not well distributed between the different groups as shown in table 1. This raises the question whether the study should be called "a randomized trial". The study uses the term "VO2max". In fact the method section reads as if only an "estimated VO2max" had been determined using a population derived nomogram for a heart rate to power output relation and therefore by a method that is irrelevant for the determination of GH-induced intra-individual differences in VO2max. Concerning the so called "significant" improvement in the Wingate value as one among four other secondary outcome variables for physical performance, it is noteworthy that the authors corrected for multiple comparisons across the different groups by a not very conservative Holm correction, while there was no correction against the number of different secondary outcome variables. We speculate here, that the journal would not have taken publication of this work into consideration if the study was related to a clinically relevant outcome measure. The study is just about 9.6 sec over 100m and this does not hurt any patient. It may just do some harm to athletes which are not within the scope of the journal.

References

1.Yarasheski K, Campbell J, Smith K, Rennie M, Holloszy J and Bier D. Effect of growth hormone and resistance exercise on muscle growth in young men. Am. J. Physiol. 262, 1992.

2.Yarasheski K, Zachwieja J, Angelopoulos T and Bier D. Short-term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters. J. Appl. Physiol. 74(6): 3073-3076, 1993.

3.Bedu M, Fellmann N, Spielvogel H, Falgairette G, Van Praagh E, Coudert J. Force-velocity and 30-s Wingate tests in boys at high and low altitudes. J. Appl. Physiol. 70(3): 1031~1037.1991.

Conflict of Interest:

None

Wingate performance and what it means in sports
Posted on June 6, 2010
Ken K.Y. Ho
Pituitary Research Unit, Garvan Institute of Medical Research
Conflict of Interest: None Declared

Mr. Sorensen and Mr Tobias have voiced joined concerns at the interpretation and media communication of our findings centred on a sentence in the Discussion of our paper. The issue centres on what an improvement in Wingate performance means.

Wingate test performance depends on all available forms of muscle energy supply and is primarily a measure of power and anaerobic capacity (1). In the context of broad performance categories assessed in our study, it is the form of testing that is most closely aligned to sprint events (not endurance running, weight lifting or high jump). We did not state that Wingate test and the capacity to sprint are 'equivalent measures' as misunderstood by Sorensen. While strength and power are determinants of sprint capacity (2), we found no evidence that either was enhanced by GH, leading us to postulate that the anaerobic energy required to drive contractile muscle function may be increased by GH. Indeed several studies have demonstrated a positive relationship between Wingate anaerobic capacity and sprint performance (3, 4).

Having stated 'we do not know how an improvement in Wingate test performance translates to performance in the sporting field', our speculation as to what this might mean in a sprint event is based on mechanistic and conceptual extrapolation. To cast this as an unsubstantiated claim appears to be a misreading of a considered deduction that has passed the most stringent standards of expert review.

Tobias has additionally raised issues concerning training bias, analysis and performance methodology. In suggesting that the unequal distribution in training quantity may have influenced the finding that GH improved Wingate performance, he infers that such a bias, if present is of sufficient magnitude to overcome the rigors of stringent randomization within a double-blind placebo-controlled design. This contention is plausible only if there is evidence that the level of training influences the measures of performance to GH, and on Wingate performance only, for which there is none. Tobias is critical of the use of Holm's method for multiple group comparison but does not offer an alternative. We employed several statistical methods including Tukey and Bonferroni corrections all of which gave similar findings but settled for Holm's method during review discussions with the Journal's statistician. Estimated VO2 max from a population derived nomogram is a validated time-honoured method. Direct measurement improves accuracy and its employment may have tightened the variance but would not have changed the outcome that VO2 max was not affected by GH, a finding in agreement with previous studies assessing the performance effects of GH in athletes (5).

We agree that challenges remain in bridging the gulf between scientific findings and media communication. Selected and simplified information in a compressed media platform can distort as the reaction to one selected sentence can.

References

1. Green S. Measurement of anaerobic work capacities in humans. Sports Med. 1995 Jan;19(1):32-42.

2. Cronin JB, Hansen KT. Strength and power predictors of sports speed. J Strength Cond Res. 2005 May;19(2):349-57.

3. Meckel Y, Machnai O, Eliakim A. Relationship among repeated sprint tests, aerobic fitness, and anaerobic fitness in elite adolescent soccer players. J Strength Cond Res. 2009 Jan;23(1):163-9.

4. Patton JF, Duggan A. An evaluation of tests of anaerobic power. Aviat Space Environ Med. 1987 Mar;58(3):237-42.

5. Liu H, Bravata DM, Olkin I, Friedlander A, Liu V, Roberts B, et al. Systematic review: the effects of growth hormone on athletic performance. Annals of internal medicine. 2008 May 20;148(10):747-58.

Conflict of Interest:

None declared

Additional Research is Needed on Growth Hormone
Posted on November 17, 2010
Mark A Troxler DO MBA FACP FACSM
American College Sports Medicine
Conflict of Interest: None Declared

The Anti-Doping Interest Group for the American College Sports Medicine met on June 3, 2010 in Baltimore and discussed Dr Mainhardt, et al work on the effects of growth hormone. As a group we had several concerns about this work. First, it was not a double blinded study. Also the statistician had access to the randomization and was influential in which athlete received growth hormone. The growth hormone was only administered for 6 weeks and not 8 weeks as advertised in the abstract and was administer by the athlete which may or may not have actually been given. The exercise regimen that was recommended was not observed and only asked of participants to continue. Finally, the athletes were treated differently when they performed the Wingate test as opposed to the other performance measures. The athletes were under verbal encouragement only for this test, which consequently was the only test that showed an improvement with the administration of growth hormone. We feel that these defects in the study reduce the reliability of these results.

Conflict of Interest:

None declared

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Summary for Patients

Effects of Growth Hormone Doping on Athletic Performance

The summary below is from the full report titled “The Effects of Growth Hormone on Body Composition and Physical Performance in Recreational Athletes. A Randomized Trial.” It is in the 4 May 2010 issue of Annals of Internal Medicine (volume 152, pages 568-577). The authors are U. Meinhardt, A.E. Nelson, J.L. Hansen, V. Birzniece, D. Clifford, K.C. Leung, K. Graham, and K.K.Y. Ho.

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