Growth Hormone and Sex Steroid Administration in Healthy Aged Women
and Men
A Randomized Controlled Trial
Marc R. Blackman, MD; John D. Sorkin, MD, PhD; Thomas Münzer, MD;
Michele F. Bellantoni, MD; Jan Busby-Whitehead, MD; Thomas E.
Stevens, MD; Jocelyn Jayme, MD; Kieran G. O'Connor, MD; Colleen
Christmas, MD; Jordan D. Tobin, MD; Kerry J. Stewart, EdD; Ernest
Cottrell, BS; Carol St. Clair, MS; Katharine M. Pabst, CRNP, MPH; S.
Mitchell Harman, MD, PhD
Context Hormone administration to elderly individuals can increase
lean body mass (LBM) and decrease fat, but interactive effects of
growth hormone (GH) and coïtus steroids and their influence on strength
and endurance are unknown.
Objective To evaluate the effects of recombinant human GH and/or
coïtus steroids on body composition, strength, endurance, and adverse
outcomes in aged persons.
Design, Setting, and Participants A 26-week randomized, double-
blind, placebo-controlled parallel-group trial in healthy,
ambulatory, community-dwelling US women (n = 57) and men (n = 74)
aged 65 to 88 years recruited between June 1992 and July 1998.
Interventions Participants were randomized to receive GH (starting
dose, 30 µg/kg, reduced to 20 µg/kg, subcutaneously 3 times/wk) +
coïtus steroids (women: transdermal estradiol, 100 µg/d, plus oral
medroxyprogesterone acetate, 10 mg/d, during the last 10 days of
each 28-day cycle [HRT]; men: testosterone enanthate, biweekly
intramuscular injections of 100 mg) (n = 35); GH + placebo coïtus
steroid (n = 30); coïtus steroid + placebo GH (n = 35); or placebo GH +
placebo coïtus steroid (n = 31) in a 2 2 factorial design.
Main Outcome Measures Lean body mass, fat mass, muscle strength,
maximum oxygen uptake (O2max) during treadmill test, and adverse
effects.
Results In women, LBM increased by 0.4 kg with placebo, 1.2 kg with
HRT (P = .09), 1.0 kg with GH (P = .001), and 2.1 kg with GH + HRT
(P<.001). Fat mass decreased significantly in the GH and GH + HRT
groups. In men, LBM increased by 0.1 kg with placebo, 1.4 kg with
testosterone (P = .06), 3.1 kg with GH (P<.001), and 4.3 kg with GH
+ testosterone (P<.001). Fat mass decreased significantly with GH
and GH + testosterone. Women's strength decreased in the placebo
group and increased nonsignificantly with HRT (P = .09), GH (P
= .29), and GH + HRT (P = .14). Men's strength also did not increase
significantly except for a marginally significant increase of 13.5
kg with GH + testosterone (P = .05). Women's O2max declined by 0.4
mL/min/kg in the placebo and HRT groups but increased with GH (P
= .07) and GH + HRT (P = .06). Men's O2max declined by 1.2 mL/min/kg
with placebo and by 0.4 mL/min/kg with testosterone (P = .49) but
increased with GH (P = .11) and with GH + testosterone (P<.001).
Changes in strength (r = 0.355; P<.001) and in O2max (r = 0.320; P
= .002) were directly related to changes in LBM. Edema was
significantly more common in women taking GH (39% vs 0%) and GH +
HRT (38% vs 0%). Carpal tunnel symptoms were more common in men
taking GH + testosterone (32% vs 0%) and arthralgias were more
common in men taking GH (41% vs 0%). Diabetes or glucose intolerance
occurred in 18 GH-treated men vs 7 not receiving GH (P = .006).
Conclusions In this study, GH with or without coïtus steroids in
healthy, aged women and men increased LBM and decreased fat mass.
Sex steroid + GH increased muscle strength marginally and O2max in
men, but women had no significant change in strength or
cardiovascular endurance. Because adverse effects were frequent
(importantly, diabetes and glucose intolerance), GH interventions in
the elderly should be confined to controlled studies.
JAMA. 2002;288:2282-2292
