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Single and Combined Effects of Growth Hormone and Testosterone Administration on Measures of Body Composition, Physical Performance, Mood, Sexual Function, Bone Turnover, and Muscle Gene Expression in Healthy Older Men

Departments of Internal Medicine (K.T.B., A.L.W., D.A.F., J.D.V.), Human Services (K.T.B., A.L.W.), Health Evaluation Sciences (J.T.P.), and Surgery (J.B.H.), General Clinical Research Center (K.T.B., A.L.W., J.T.P., J.D.V.), and Center for Biomathematical Technology (J.D.V.), University of Virginia, Charlottesville, Virginia 22908; Department of Geriatrics (A.G.), Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298; and Department of Internal Medicine (R.J.U.), Division of Endocrinology, University of Texas Medical Branch, Galveston, Texas 77555

Address all correspondence and requests for reprints to: Arthur Weltman, Ph.D., Exercise Physiology Laboratory/Memorial Gym, University of Virginia, Charlottesville, Virginia 22904. E-mail: alw2v{at}virginia.edu.

Abstract

We examined the effects of GH and/or testosterone (T) administration on body composition, performance, mood, sexual function, bone turnover, and muscle-gene expression in healthy older men. Ten men [mean (SEM) age, 68 (2.5) yr; height, 171.5 (2.4) cm; and weight, 80 (3.0) kg] completed each of the following 1-month, double-blind interventions after a baseline (B) study in randomized order with an intervening 3-month washout: transdermal T patch (5.0 mg/daily); recombinant human GH (6.25 µg/kg sc daily); and combined hormones (GHT). ANOVA with repeated measures was used to evaluate interventional effects. Integrated serum GH concentrations [mean (SEM)] were elevated comparably by GH and GHT: [B = 363 (55), GH = 1107 (120), T = 459 (131), and GHT = 1189 (46) µg/liter·min; P < 0.0001]. Serum IGF-I concentrations also increased commensurately after GH and GHT: [B = 168 (14), GH = 285 (16), T = 192 (25), and GHT = 294 (25) µg/liter; P < 0.0001]. GHT administration increased total estradiol: [B = 110 (20), GH = 106 (13), T = 129 (13), and GHT = 153 (17) pmol/liter; P < 0.02], and both T and GHT elevated free T: [B = 12 (2.1), GH = 11 (1.5), T = 22 (2.8), and GHT = 24 (2.5) pg/ml; P < 0.0001]. No significant changes occurred in strength, flexibility, percentage body fat, or sexual function and mood. However, fat-free mass increased under combined GHT exposure: [B = 55 (1.3), GH = 56 (1.1), T = 55 (1.5), GHT = 57 (1.7) kg; P < 0.03]. Balance improved in response to GH intervention (P < 0.05), as did 30-m walk time during T and GHT interventions [B = 6.6 (0.3), GH = 6.2 (0.7), T = 5.9 (0.3), GHT = 5.5 (0.3) sec; P = 0.04] and stair climb time for all three interventions [B = 32.2 (1.4), GH = 29.8 (1.2), T = 30.5 (1.4), and GHT = 29.9 (1.2) sec (P = 0.0034), wherein the effects of GH, T, and GHT were different from that of B]. Muscle IGF-I gene expression increased by 1.9-fold during GH administration and by 2.3-fold during GHT administration (P < 0.05, compared with B). Myostatin and androgen receptor gene expression were not affected. Serum osteocalcin increased in response to the GH and GHT interventions: [B = 4.8 (0.52), GH = 5.7 (0.54), T = 4.7 (0.33), and GHT = 5.5 (0.39); P <0.009]. There were no significant adverse events during 30 patient-months of intervention. We conclude that 1 month of GH and/or T administration improves certain measures of balance and physical performance in older men and increases muscle IGF-I gene expression.

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