Growth hormone responses to low-dose physostigmine in elderly vs. young women and men

Growth hormone (GH) secretion is a sensitive measure of CNS cholinergic neurotransmission, and GH decreases considerably with age. Cholinesterase inhibitors, which increase acetylcholine concentrations, have been used in elderly subjects to investigate the neuroendocrine effects of aging and Alzheimer's disease. However, there have been only a few studies of a potential sex difference in GH responses to cholinesterase inhibitors in elderly subjects, with mixed results.

We therefore administered low-dose physostigmine (PHYSO), a cholinesterase inhibitor, to normal, non-hormone-replaced, elderly women and men, to ascertain a potential sex difference in GH response. We hypothesized: (1) elderly women and men would have similar hormone responses, because of relatively low circulating estrogen in the women, and (2) the elderly women would have significantly lower baseline GH and GH responses to cholinergic challenge than the young women we studied previously.

Normal elderly women and men > or =65 years of age meeting stringent inclusion and exclusion criteria were studied on three test days, 4-7 days apart, by serial blood sampling for several hours for baseline GH, followed by administration of low-dose PHYSO (first and third days) or saline (second day) at 18:00 h. Frequent blood sampling was continued for several hours. Plasma GH and hypothalamo-pituitary-adrenal cortical hormones were measured in each sample.

PHYSO administration produced no side effects in about half the elderly subjects and mild side effects in the other half, with no significant female-male differences and no significant relationship between the presence or absence of side effects and GH response. PHYSO significantly increased GH compared to saline, to a similar degree in the elderly women and men. The elderly women had a significantly greater GH response to PHYSO than did the young women, whereas GH responses were similar in the elderly and young men.

These results indicate similar GH responses to low-dose PHYSO in elderly women compared to elderly men, and a significantly greater GH response in elderly women compared to young women. A likely mechanism is increased sensitivity of central cholinergic systems that inhibit somatostatin and/or enhance GHRH release from the hypothalamus.