The age-related down-regulation of the growth hormone/insulin-like growth factor-1 axis in the elderly male is reversed considerably by donepezil, a drug for Alzheimer's disease.
GH secretion declines by 14%/decade of adult life, leading to the suggestion that people over the age of 60 years are functionally GH deficient. Recently, rivastigmine, a novel cerebral selective cholinesterase-inhibitor (ChEI), was shown to be a powerful drug to enhance GH release to repeated GHRH stimulation in healthy elderly human subjects. The present study was designed as a randomised controlled trial to evaluate long term effects of donepezil, a cerebral selective ChEI, on basal GH and IGF-1 levels and on GH response to GHRH (1 microg/kg i.v., GHRH test) before and after an 8-week donepezil treatment period. Donepezil was given orally 5 mg per day for 4 weeks and 10 mg per day for another 4 weeks. Twenty four healthy male volunteers (n=2 x 12, placebo group vs. donepezil group, age: 61-70 years) were studied. Donepezil treatment group: basal GH levels taken at 08:30 a.m. doubled from 0.4+/-0.3 to 0.8+/-0.4 ng/ml (p=0.008). GHRH-test: GH-AUC was 318+/-227 ng/ml/h and increased by 53% to 485+/-242 ng/ml/h (p=0.009). Total serum IGF-1 levels, taken simultaneously with the basal GH levels, showed a considerable increase, too: the baseline IGF-1 levels increased by 31% from 84+/-19 to 110+/-21 ng/ml (p=0.007). This study demonstrated that the age-related down-regulation of the GH/IGF-1 axis is reversed considerably by donepezil in the elderly male. Future investigation will reveal whether such a new therapeutic intervention can delay the onset or even reverse some manifestations of the somatopause in the long term and evaluate its benefit/risk ratio concerning new treatment implications.
Obermayr
Rudolf P
RP
Ludwig Boltzmann Institute for Aging Research, Donauspital, Sozialmedizinisches Zentrum Ost der Stadt Wien, Langobardenstrasse 122, A-1220 Wien, Austria. rudolf.obermayr@wienkav.at
Mayerhofer
Lothar
L
Knechtelsdorfer
Maarten
M
Mersich
Nicole
N
Huber
Erik R
ER
Geyer
Georg
G
Tragl
Karl-Heinz
KH
D000368:Aged; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy; D000704:Analysis of Variance; D019540:Area Under Curve; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*; D016037:Single-Blind Method
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D007334:Insulin-Like Growth Factor I; D000077265:Donepezil; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone