Effect of short-term DHEA supplementation on serum and hippocampal estrogen concentrations in perimenopausal female rhesus macaques.

The hippocampus of rhesus macaques expresses genes that encode key enzymes involved in the intracrine conversion of dehydroepiandrosterone (DHEA) to estradiol. Therefore, it is plausible that supplementary DHEA may enhance hippocampal estradiol concentrations and help to compensate for the marked postmenopausal attenuation of circulating estrogen levels. To test this hypothesis, we used LC-MS/MS to measure estradiol and estrone concentrations in the serum and hippocampus of young and old perimenopausal female rhesus macaques, as well as old perimenopausal females that received daily DHEA (5 mg) oral supplementation for 1 week. Despite lower concentrations of these estrogens in the serum of the older animals, their concentrations in the hippocampus did not show any obvious differences due to age or to DHEA supplementation. The results suggest that de novo estrogen synthesis in the brain may compensate for the perimenopausal loss of estrogens in the circulation even without supplemental DHEA.