This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (142)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in JAMA  Topic Collections  • Aging/ Geriatrics  • Men's Health  • Men's Health, Other  • Exercise  • Women's Health  • Menopause  • Randomized Controlled Trial  • Alert me on articles by topic  Social Bookmarking   What's this?

A Randomized Controlled Trial

Marc R. Blackman, MD; John D. Sorkin, MD, PhD; Thomas Münzer, MD; Michele F. Bellantoni, MD; Jan Busby-Whitehead, MD; Thomas E. Stevens, MD; Jocelyn Jayme, MD; Kieran G. O'Connor, MD; Colleen Christmas, MD; Jordan D. Tobin, MD; Kerry J. Stewart, EdD; Ernest Cottrell, BS; Carol St. Clair, MS; Katharine M. Pabst, CRNP, MPH; S. Mitchell Harman, MD, PhD

JAMA. 2002;288:2282-2292.

Context  Hormone administration to elderly individuals can increase lean body mass (LBM) and decrease fat, but interactive effects of growth hormone (GH) and sex steroids and their influence on strength and endurance are unknown.

Objective  To evaluate the effects of recombinant human GH and/or sex steroids on body composition, strength, endurance, and adverse outcomes in aged persons.

Design, Setting, and Participants  A 26-week randomized, double-blind, placebo-controlled parallel-group trial in healthy, ambulatory, community-dwelling US women (n = 57) and men (n = 74) aged 65 to 88 years recruited between June 1992 and July 1998.

Interventions  Participants were randomized to receive GH (starting dose, 30 µg/kg, reduced to 20 µg/kg, subcutaneously 3 times/wk) + sex steroids (women: transdermal estradiol, 100 µg/d, plus oral medroxyprogesterone acetate, 10 mg/d, during the last 10 days of each 28-day cycle [HRT]; men: testosterone enanthate, biweekly intramuscular injections of 100 mg) (n = 35); GH + placebo sex steroid (n = 30); sex steroid + placebo GH (n = 35); or placebo GH + placebo sex steroid (n = 31) in a 2 x 2 factorial design.

Main Outcome Measures  Lean body mass, fat mass, muscle strength, maximum oxygen uptake (O₂max) during treadmill test, and adverse effects.

Results  In women, LBM increased by 0.4 kg with placebo, 1.2 kg with HRT (P = .09), 1.0 kg with GH (P = .001), and 2.1 kg with GH + HRT (P<.001). Fat mass decreased significantly in the GH and GH + HRT groups. In men, LBM increased by 0.1 kg with placebo, 1.4 kg with testosterone (P = .06), 3.1 kg with GH (P<.001), and 4.3 kg with GH + testosterone (P<.001). Fat mass decreased significantly with GH and GH + testosterone. Women's strength decreased in the placebo group and increased nonsignificantly with HRT (P = .09), GH (P = .29), and GH + HRT (P = .14). Men's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone (P = .05). Women's O₂max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH (P = .07) and GH + HRT (P = .06). Men's O₂max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone (P = .49) but increased with GH (P = .11) and with GH + testosterone (P<.001). Changes in strength (r = 0.355; P<.001) and in O₂max (r = 0.320; P = .002) were directly related to changes in LBM. Edema was significantly more common in women taking GH (39% vs 0%) and GH + HRT (38% vs 0%). Carpal tunnel symptoms were more common in men taking GH + testosterone (32% vs 0%) and arthralgias were more common in men taking GH (41% vs 0%). Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH (P = .006).

Conclusions  In this study, GH with or without sex steroids in healthy, aged women and men increased LBM and decreased fat mass. Sex steroid + GH increased muscle strength marginally and O₂max in men, but women had no significant change in strength or cardiovascular endurance. Because adverse effects were frequent (importantly, diabetes and glucose intolerance), GH interventions in the elderly should be confined to controlled studies.

Author Affiliations: Divisions of Endocrinology and Metabolism (Drs Blackman and Jayme, Mr Cottrell, and Mss St. Clair and Pabst), Cardiology (Dr Stewart), and Geriatric Medicine and Gerontology (Drs Bellantoni, Busby-Whitehead, Stevens, O'Connor, and Christmas), Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md; the Endocrine (Drs Münzer and Harman), Metabolism (Dr Sorkin), and Applied Physiology (Dr Tobin) Sections, Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, and National Center for Complementary and Alternative Medicine (Dr Blackman and Ms Pabst), National Institutes of Health, Bethesda, Md; Department of Medicine, University of Maryland School of Medicine, Baltimore (Dr Sorkin and Ms St. Clair); Burgerspital, St Gallen, Switzerland (Dr Münzer); Division of Geriatric Medicine, University of North Carolina School of Medicine, Chapel Hill (Dr Busby-Whitehead); Division of Geriatric Medicine, University of Southern Alabama School of Medicine, Mobile (Dr Stevens); Louth Hospital, County Louth, Ireland (Dr O'Connor); and Kronos Research Institute, Phoenix, Ariz (Dr Harman).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

Use of Growth Hormone in Elderly Individuals
Eric Braverman
JAMA. 2003;290(4):462.
EXTRACT | FULL TEXT  

Use of Growth Hormone in Elderly Individuals
Saul Malozowski
JAMA. 2003;290(4):462.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis
Doessing et al.
J. Physiol. 2010;588:341-351.
ABSTRACT | FULL TEXT  

The Effects of Growth Hormone (GH) Treatment on GH and Insulin/IGF-1 Signaling in Long-Lived Ames Dwarf Mice
Masternak et al.
J Gerontol A Biol Sci Med Sci 2010;65A:24-30.
ABSTRACT | FULL TEXT  

N-Terminal Propeptide of Type III Procollagen as a Biomarker of Anabolic Response to Recombinant Human GH and Testosterone
Bhasin et al.
J. Clin. Endocrinol. Metab. 2009;94:4224-4233.
ABSTRACT | FULL TEXT  

Growth Hormone and Sex Steroid Effects on Serum Glucose, Insulin, and Lipid Concentrations in Healthy Older Women and Men
Munzer et al.
J. Clin. Endocrinol. Metab. 2009;94:3833-3841.
ABSTRACT | FULL TEXT  

Statement by the Growth Hormone Research Society on the GH/IGF-I Axis in Extending Health Span
Thorner
J Gerontol A Biol Sci Med Sci 2009;64A:1039-1044.
ABSTRACT | FULL TEXT  

Testosterone and Growth Hormone Improve Body Composition and Muscle Performance in Older Men
Sattler et al.
J. Clin. Endocrinol. Metab. 2009;94:1991-2001.
ABSTRACT | FULL TEXT  

Potential Application of Essential Amino Acid Supplementation to Treat Sarcopenia in Elderly People
Henderson et al.
J. Clin. Endocrinol. Metab. 2009;94:1524-1526.
FULL TEXT  

Growth hormone, menopause and ageing: no definite evidence for 'rejuvenation' with growth hormone
Fanciulli et al.
Hum Reprod Update 2009;15:341-358.
ABSTRACT | FULL TEXT  

Effects of an Oral Growth Hormone Secretagogue in Older Adults
White et al.
J. Clin. Endocrinol. Metab. 2009;94:1198-1206.
ABSTRACT | FULL TEXT  

Regulation of Myogenic Differentiation by Androgens: Cross Talk between Androgen Receptor/ {beta}-Catenin and Follistatin/Transforming Growth Factor-{beta} Signaling Pathways
Singh et al.
Endocrinology 2009;150:1259-1268.
ABSTRACT | FULL TEXT  

Effects of an Oral Ghrelin Mimetic on Body Composition and Clinical Outcomes in Healthy Older Adults: A Randomized Trial
Nass et al.
ANN INTERN MED 2008;149:601-611.
ABSTRACT | FULL TEXT  

The Effects of Growth Hormone and/or Testosterone on Whole Body Protein Kinetics and Skeletal Muscle Gene Expression in Healthy Elderly Men: A Randomized Controlled Trial
Giannoulis et al.
J. Clin. Endocrinol. Metab. 2008;93:3066-3074.
ABSTRACT | FULL TEXT  

Pharmacodynamics of Growth Hormone Abuse Biomarkers and the Influence of Gender and Testosterone: A Randomized Double-Blind Placebo-Controlled Study in Young Recreational Athletes
Nelson et al.
J. Clin. Endocrinol. Metab. 2008;93:2213-2222.
ABSTRACT | FULL TEXT  

Effects of short-term GH supplementation and treadmill exercise training on physical performance and skeletal muscle apoptosis in old rats
Marzetti et al.
Am. J. Physiol. Regul. Integr. Comp. Physiol. 2008;294:R558-R567.
ABSTRACT | FULL TEXT  

The Growth Hormone/Insulin-Like Growth Factor-I Axis in Exercise and Sport
Gibney et al.
Endocr. Rev. 2007;28:603-624.
ABSTRACT | FULL TEXT  

Long-term testosterone supplementation augments overnight growth hormone secretion in healthy older men
Muniyappa et al.
Am. J. Physiol. Endocrinol. Metab. 2007;293:E769-E775.
ABSTRACT | FULL TEXT  

Systematic Review: The Safety and Efficacy of Growth Hormone in the Healthy Elderly
Liu et al.
ANN INTERN MED 2007;146:104-115.
ABSTRACT | FULL TEXT  

Pharmacological and X-Ray Structural Characterization of a Novel Selective Androgen Receptor Modulator: Potent Hyperanabolic Stimulation of Skeletal Muscle with Hypostimulation of Prostate in Rats
Ostrowski et al.
Endocrinology 2007;148:4-12.
ABSTRACT | FULL TEXT  

Dehydroepiandrosterone Secretion in Healthy Older Men and Women: Effects of Testosterone and Growth Hormone Administration in Older Men
Muniyappa et al.
J. Clin. Endocrinol. Metab. 2006;91:4445-4452.
ABSTRACT | FULL TEXT  

Baseline Characteristics and Effects of Growth Hormone Therapy over Two Years in Younger and Elderly Adults with Adult Onset GH Deficiency
Franco et al.
J. Clin. Endocrinol. Metab. 2006;91:4408-4414.
ABSTRACT | FULL TEXT  

Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice
Axell et al.
Am. J. Physiol. Endocrinol. Metab. 2006;291:E506-E516.
ABSTRACT | FULL TEXT  

Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline
Molitch et al.
J. Clin. Endocrinol. Metab. 2006;91:1621-1634.
ABSTRACT | FULL TEXT  

Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men
Munzer et al.
Am. J. Physiol. Endocrinol. Metab. 2006;290:E1006-E1013.
ABSTRACT | FULL TEXT  

The Effects of Growth Hormone and/or Testosterone in Healthy Elderly Men: A Randomized Controlled Trial
Giannoulis et al.
J. Clin. Endocrinol. Metab. 2006;91:477-484.
ABSTRACT | FULL TEXT  

Dehydroepiandrosterone Restoration of Growth Hormone Gene Expression in Aging Female Rats, in Vivo and in Vitro: Evidence for Actions via Estrogen Receptors
Iruthayanathan et al.
Endocrinology 2005;146:5176-5187.
ABSTRACT | FULL TEXT  

Adverse Events Associated With Testosterone Replacement in Middle-Aged and Older Men: A Meta-Analysis of Randomized, Placebo-Controlled Trials
Calof et al.
J Gerontol A Biol Sci Med Sci 2005;60:1451-1457.
ABSTRACT | FULL TEXT  

Provision or Distribution of Growth Hormone for "Antiaging": Clinical and Legal Issues
Perls et al.
JAMA 2005;294:2086-2090.
FULL TEXT  

The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications
Kaufman and Vermeulen
Endocr. Rev. 2005;26:833-876.
ABSTRACT | FULL TEXT  

Insulin Resistance and Muscle Strength in Older Persons
Abbatecola et al.
J Gerontol A Biol Sci Med Sci 2005;60:1278-1282.
ABSTRACT | FULL TEXT  

Minireview: Role of the Growth Hormone/Insulin-Like Growth Factor System in Mammalian Aging
Bartke
Endocrinology 2005;146:3718-3723.
ABSTRACT | FULL TEXT  

A Randomized, Placebo-Controlled Trial of Nandrolone Decanoate in Human Immunodeficiency Virus-Infected Men with Mild to Moderate Weight Loss with Recombinant Human Growth Hormone as Active Reference Treatment
Storer et al.
J. Clin. Endocrinol. Metab. 2005;90:4474-4482.
ABSTRACT | FULL TEXT  

Growth hormone and testosterone interact positively to enhance protein and energy metabolism in hypopituitary men
Gibney et al.
Am. J. Physiol. Endocrinol. Metab. 2005;289:E266-E271.
ABSTRACT | FULL TEXT  

Exogenous Testosterone (T) Alone or with Finasteride Increases Physical Performance, Grip Strength, and Lean Body Mass in Older Men with Low Serum T
Page et al.
J. Clin. Endocrinol. Metab. 2005;90:1502-1510.
ABSTRACT | FULL TEXT  

Muscle Mass, Muscle Strength, and Muscle Fat Infiltration as Predictors of Incident Mobility Limitations in Well-Functioning Older Persons
Visser et al.
J Gerontol A Biol Sci Med Sci 2005;60:324-333.
ABSTRACT | FULL TEXT  

Older Men Are as Responsive as Young Men to the Anabolic Effects of Graded Doses of Testosterone on the Skeletal Muscle
Bhasin et al.
J. Clin. Endocrinol. Metab. 2005;90:678-688.
ABSTRACT | FULL TEXT  

Inhibition of 5{alpha}-reductase blocks prostate effects of testosterone without blocking anabolic effects
Borst et al.
Am. J. Physiol. Endocrinol. Metab. 2005;288:E222-E227.
ABSTRACT | FULL TEXT  

Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment
Sinha-Hikim et al.
J. Clin. Endocrinol. Metab. 2004;89:5245-5255.
ABSTRACT | FULL TEXT  

Growing Pains
Davenport
Sci Aging Knowl Environ 2004;2004:ns5-ns5.
ABSTRACT | FULL TEXT  

Hormones and Supplements: Do They Work?: Use of Growth Hormone for Prevention or Treatment of Effects of Aging
Harman and Blackman
J Gerontol A Biol Sci Med Sci 2004;59:B652-B658.
ABSTRACT | FULL TEXT  

Anti-Aging Medicine: The Legal Issues: Anti-Aging Quackery: Human Growth Hormone and Tricks of the Trade--More Dangerous Than Ever
Perls
J Gerontol A Biol Sci Med Sci 2004;59:B682-B691.
ABSTRACT | FULL TEXT  

Antiaging Supplement Holds Promise to Halt Age-Related Cognitive Deterioration
Brown-Borg
Exp Biol Med 2004;229:367-368.
FULL TEXT  

Growth hormone: uses and abuses
Hintz
BMJ 2004;328:907-908.
FULL TEXT  

Treatment with oxandrolone and the durability of effects in older men
Schroeder et al.
J. Appl. Physiol. 2004;96:1055-1062.
ABSTRACT | FULL TEXT  

Low-Dose Recombinant Human Growth Hormone as Adjuvant Therapy to Lifestyle Modifications in the Management of Obesity
Albert and Mooradian
J. Clin. Endocrinol. Metab. 2004;89:695-701.
ABSTRACT | FULL TEXT  

Review Article: Sarcopenia: Causes, Consequences, and Preventions
Marcell
J Gerontol A Biol Sci Med Sci 2003;58:M911-M916.
ABSTRACT | FULL TEXT  

Andropause: Symptom Management for Prostate Cancer Patients Treated With Hormonal Ablation
Thompson et al.
The Oncologist 2003;8:474-487.
ABSTRACT | FULL TEXT  

Use of Growth Hormone in Elderly Individuals
Braverman
JAMA 2003;290:462-462.
FULL TEXT  

Use of Growth Hormone in Elderly Individuals
Malozowski
JAMA 2003;290:462-462.
FULL TEXT  

Claims for the anabolic effects of growth hormone: a case of the Emperor's new clothes?
Rennie
Br. J. Sports. Med. 2003;37:100-105.
ABSTRACT | FULL TEXT  

Evolutionary Medicine: From Dwarf Model Systems to Healthy Centenarians?
Longo and Finch
Science 2003;299:1342-1346.
ABSTRACT | FULL TEXT  

Can Growth Hormone Prevent Aging?
Vance
NEJM 2003;348:779-780.
FULL TEXT  

Use It or Lose It: Activity May Be the Best Treatment for Aging
Cassel
JAMA 2002;288:2333-2335.
FULL TEXT