Effects of recombinant human growth hormone on metabolic indices, body composition, and bone turnover in healthy elderly women
L Holloway, G Butterfield, RL Hintz, N Gesundheit and R Marcus
Aging Study Unit, Palo Alto Veterans Affairs Medical Center, California 94304.
We conducted a controlled trial of recombinant human GH (rhGH) in 27
healthy elderly women (66.7 +/- 3.0 yr), of whom 8 took a stable dose of
replacement estrogen throughout the study (plus estrogen group). Hormone or
placebo was given as a single daily injection. A total of 19 women were
assigned to receive rhGH at an initial daily dose of 0.043 mg/kg BW. After
several weeks, 50% dose reductions were necessitated by side-effects. The
last 7 subjects to be enrolled began treatment at this reduced level. A
total of 13 women assigned to rhGH and 14 women assigned to placebo
completed 6 months of drug treatment. In the rhGH group, 6 women took
estrogen; thus, the effects of rhGH were assessed separately by estrogen
status. Circulating insulin-like growth factor-I (IGF-I) levels were
similar at baseline (rhGH, 133 +/- 40.4 micrograms/L; placebo, 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 micrograms/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 micrograms/L).
Skinfold thickness measurements showed an 11% decrease in fat mass (P <
0.005) and a 9% decrease in percent fat after 6 months of rhGH treatment.
No significant difference in nitrogen balance was seen in either group at 6
months, but rhGH increased creatinine 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% and 75% in plus and
minus estrogen subgroups, respectively. Osteocalcin concentrations
increased by more than 60% in minus estrogen women (P < 0.05), but did
not change in the plus estrogen group. No changes were observed in
circulating type I procollagen extension peptide in either group, and no
change in any turnover marker was seen in the placebo group. rhGH did not
alter blood pressure or circulating L-T4 levels, but a transient increase
in serum T3 was observed in the minus estrogen group at 3 months. rhGH
decreased low density lipoprotein cholesterol in the minus estrogen group,
but otherwise no significant changes in circulating lipoproteins or
fibrinogen were observed. Eight women assigned to rhGH and 14
placebo-treated women remained on blinded treatment through 12
months.(ABSTRACT TRUNCATED AT 400 WORDS)
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