GH administration and discontinuation in healthy elderly men: effects on body composition, GH-related serum markers, resting heart rate and resting oxygen uptake

BACKGROUND AND OBJECTIVES GH administration results in increased lean body mass (LBM), decreased fat mass (FM) and increased energy expenditure (EE). GH therapy may therefore have potential benefits, especially in the elderly, who are known to have decreased function of the GH/IGF-I axis. Several studies have focused on effects of GH administration in the elderly in the last decade. However, very limited information is available regarding changes in body composition and EE upon GH discontinuation in the elderly. The present study therefore investigated the effects of 12 weeks of GH administration and subsequent discontinuation on body composition, resting oxygen uptake (VO2), resting heart rate (HR) and GH related serum markers in healthy elderly men. SUBJECTS AND METHODS Sixteen healthy men [age 74 +/- 1 years (mean +/- SEM), height 174.2 +/- 1.6 cm, body weight 80.7 +/- 2.6 kg, body fat 27.5 +/- 1.1%] completed the study protocol. Recombinant human GH (1.80 +/- 0.24 IU/day) was administered for 12 weeks in a single-blinded, placebo-controlled design. Body composition (dual energy X-ray absorptiometry), resting VO2 (indirect calorimetry), resting HR (telemetry) and serum IGF-I, IGF-II, IGFBP-3 and acid labile subunit (ALS) were measured at baseline, after 12 weeks of GH administration and, additionally in the GH group, 1, 2, 3, 4, 5 and 9 days after GH discontinuation. RESULTS Body weight was unchanged from baseline to 12 weeks in both groups. However, GH administration caused a decrease in FM (3.4 +/- 1.0 kg, P < 0.012), paralleled by a similar increase in LBM (3.2 +/- 0.4 kg, P < 0.0002). Resting VO2 and resting HR increased by 31 +/- 3.6% and 7.3 +/- 1.9 per minute, respectively, in the GH-group, where significant increases in serum IGF-I, IGFBP-3 and ALS also were noted. None of the above parameters changed in the placebo group. Within 2-3 days after GH discontinuation, the GH related serum markers and resting HR returned to baseline levels, whereas resting VO2 remained elevated even 9 days after GH discontinuation. In addition, GH discontinuation caused a significant decrease in body weight (1.86 +/- 0.35 kg), derived exclusively from a decrease in LBM (1.63 +/- 0.43 kg), while the decreased FM was maintained (12 weeks: 17.93 +/- 1.65 kg, +9 days: 17.74 +/- 1.62 kg). CONCLUSIONS The increases in serum IGF-I, IGFBP-3, ALS and resting heart rate induced by 12 weeks of GH administration in elderly men returned to baseline levels within 2-3 days after GH discontinuation. However, resting VO2 remained elevated for a longer period. GH administration reduced fat mass but maintained body weight by increasing lean body mass. In contrast, 9 days of GH discontinuation reduced body weight exclusively by reducing lean body mass.