EFFECTS OF RECOMBINANT HUMAN GROWTH-HORMONE ON METABOLIC INDEXES, BODY-COMPOSITION, AND BONE TURNOVER IN HEALTHY ELDERLY WOMEN

We conducted a controlled trial of recombinant human GH (rhGH) in 27 h ealthy elderly women (66.7 +/- 3.0 yr), of whom 8 took a stable dose o f replacement estrogen throughout the study (plus estrogen group). Hor mone or placebo was given as a single daily injection. A total of 19 w omen were assigned to receive rhGH at an initial daily dose of 0.043 m g/kg BW. After several weeks, 50% dose reductions were necessitated by side-effects. The last 7 subjects to be enrolled began treatment at t his reduced level. A total of 13 women assigned to rhGH and 14 women a ssigned to placebo completed 6 months of drug treatment. In the rhGH g roup, 6 women took estrogen; thus, the effects of rhGH were assessed s eparately by estrogen status. Circulating insulin-like growth factor-I (IGF-I) levels were similar at baseline (rhGH, 133 +/- 40.4 mu g/L; p lacebo, 128 +/- 13). rhGH increased IGF-I and IGF-I-binding protein-3 (IGFBP-3) in all subjects [6 month IGF-I in plus estrogen women, 230 /- 25.4 mu g/L; in those not receiving estrogen (minus estrogen), 308 +/- 21.3]. No changes in IGF-I or IGFBP-3 occurred with placebo (IGF-I , 144 +/- 21.3 mu g/L). Skinfold thickness measurements showed an 11% decrease in fat mass (P < 0.005) and a 9% decrease in percent fat afte r 6 months of rhGH treatment. No significant difference in nitrogen ba lance was seen in either group at 6 months, but rhGH increased creatin ine clearance by 9.2% (P < 0.05). rhGH dramatically increased markers of bone turnover, with more pronounced effects in minus estrogen women . Hydroxyproline excretion increased by 20% and 80%, and pyridinoline excretion increased by 44% acid 75% in plus and minus estrogen subgrou ps, respectively. Osteocalcin concentrations increased by more than 60 % in minus estrogen women (P < 0.05), but did not change in the plus e strogen group. No changes were observed in circulating type I procolla gen extension peptide in either group, and no change in any turnover m arker was seen in the placebo group, rhGH did not alter blood pressure or circulating L-T-4 levels, but a transient increase in serum T-3 wa s observed in the minus estrogen group at 3 months. rhGH decreased low density lipoprotein cholesterol in the minus estrogen group, but othe rwise no significant changes in circulating lipoproteins or fibrinogen were observed. Eight women assigned to rhGH and 14 placebo-treated wo men remained on blinded treatment through 12 months. Analysis of this cohort showed persistence of the 6 month changes in IGF-I, IGFBP-3, an d bone turnover markers. rhGH did not increase bone mineral density at the lumbar spine or hip, but the placebo group experienced 1.7% and 3 .0% decreases in bone mineral density at the trochanter and Ward's tri angle. We conclude that rhGH can be administered to healthy elderly wo men without obvious adverse effects on major cardiovascular risk facto rs, and the effects of such treatment are modulated by concurrent estr ogen replacement therapy, rhGH is a powerful initiator of bone remodel ing, but alone is unlikely to achieve major improvement in bone mass. The clinical utility of rhGH in elderly women is constrained by a high prevalence of side-effects, particularly fluid retention and carpal t unnel syndrome.