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 micro g/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) micro g/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) micro g/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.

To test whether concentrations of estradiol and testosterone predict GH responses to mechanistically distinct secretagogues in healthy older adults, we studied 16 volunteers (n = 10 men, n = 6 women, age 49-72 yr) in each of six randomly ordered sessions as follows: 1) saline; 2) l-arginine; 3) aerobic exercise; 4) GHRH; 5) GH-releasing peptide (GHRP)-2; and 6) somatostatin-induced rebound. Statistical comparisons disclosed that stimulus type (P < 0.001) and the interaction between gender and stimulus type (P = 0.023) determine GH secretion. In women, each secretagogue, except exercise and somatostatin-induced rebound, stimulated GH secretion by 2.6- to 6.4-fold over saline/rest (P < 0.023). In men, somatostatin-induced rebound drove GH secretion by 4.6-fold (P = 0.004), exercise by 16-fold (P < 0.001), and other secretagogues by 18- to 109-fold over saline/rest (each P < 0.001). Gender comparisons disclosed greater GH secretion in men than women after somatostatin-induced rebound (P = 0.008) and GHRP-2 injection (P < 0.001) and conversely greater GH secretion in women than men after saline (P = 0.013). Regression analysis showed that individual concentrations of estradiol (r = 0.80, P = 0.002) and testosterone (r = 0.63, P = 0.008) and their combination (r = 0.86, P < 0.001) strongly predict responses to GHRP-2 only. We conclude that among healthy middle-aged and older adults, the action of GHRP is uniquely determined by gender and physiological concentrations of testosterone and estradiol.

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