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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).

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