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We previously demonstrated that the reversible cholinesterase inhibitor, physostigmine (PHYSO), administered to normal young adult women and risen (average age 35 years) at a dose that produced few or no side effects, resulted in a sex difference (sexual diergism) in hypothalamo-pituitary-adrenal cortical (HPA) axis responses: Plasma ACTH(1-39), cortisol, and arginine vasopressin (AVP) concentrations increased to a significantly greater extent in the area than in the women. To explore the effect of age on these sexually diergic hormone responses, in the present sturdy we used the snare dose of PHYSO (8 mug/kg IV) to stimulate ACTH(1-39), cortisol, and AVP secretion in normal elderly, port-estrogen-replaced women and elderly risen (average ages 73 years and 70 years, respectively). The subjects underwent three felt sessions 5-7 days apart: PHYSO, saline control, and a second session of PHYSO. Serial blood samples were taken for hormone analyses before and after pharmacologic challenge.

As with the previously studied younger subjects, PHYSO administration produced no side effects its about half the elderly subjects and mild side effects in the outer half, with no significant female-male differences. The hormone responses were 2-5 fold greater in the elderly subjects than in the younger subjects, but in contrast to the younger subjects, the elderly risen did not have significantly greater hormone responses to PHYSO administration than did the elderly women. The ACTH1-39 and AVP responses to PHYSO for the two sessions were significantly positively correlated in the men (+0.96, +0.91) but not in the women. Norse of the hormone responses was significantly correlated with the presence or absence of side effects in either group of subjects.

These results indicate a greater sensitivity of the HPA axis to low-dose PHYSO, and a loss of overall sex differences in hormone responses, in elderly compared with younger subjects. The lack of a difference its side effects between the elderly women and risen and the lack of significant correlations between presence or absence of side effects arid hormone responses suggest that the increase in hormone responses with aging is duo to correspondingly increased responsiveness of central cholinergic systems and/or the HPA axis, and not to a nonspecific stress response. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.