Background. Considerable endocrine and non-endocrine evidence supports the hypothesis of increased cholinergic activity relative to noradrenergic activity in major depression. We previously reported functional sex differences (sexual diergism) in hypothalamo–pituitary–adrenal cortical (HPA) hormone responses to the administration of low-dose physostigmine (PHYSO), a cholinesterase inhibitor, in 12 female and eight male unipolar major depressives and 12 female and eight male individually matched control subjects. Because growth hormone (GH) secretion also is influenced by cholinergic mechanisms, we measured GH in the samples from this study.

Method. Subjects underwent four test sessions 5–7 days apart: PHYSO (8 μg/kg i.v.), arginine vasopressin (AVP) (0·08 U/kg i.m.), PHYSO+AVP and saline control. The AVP was administered as a second stimulus to HPA axis hormone secretion. PHYSO and AVP produced no side-effects in about half the subjects and predominantly mild side-effects in the other half, with no significant patient–control differences. Point biserial correlations between side-effects (absent or present) after PHYSO and the corresponding GH responses were non-significant in all groups.

Results. Afternoon baseline GH was significantly higher in the women than in the men, but it was not significantly different between the female or the male patients and their respective matched controls. AVP administration had no effect on GH. PHYSO administration acutely stimulated GH secretion, to a similar degree in the women and men. The depressed patients as a group had a significantly greater average post-PHYSO GH response than did their controls, with a trend toward a significant sex×diagnosis interaction: The female depressives had a significantly greater GH response than their female controls, whereas the male depressives had a similar GH response as their male controls.

Conclusions. These findings suggest sexual diergism (functional sex differences) in baseline and cholinergically stimulated plasma GH measures between major depressives and matched normal controls.