Salivary cortisol and explicit memory in postmenopausal women using hormone replacement therapy

Circulating cortisol levels are known to influence explicit memory in humans and other primates. The present study investigated salivary cortisol and its association with explicit memory performance in 99 postmenopausal women (64 treated with conjugated equine estrogens or estradiol, and 35 matched controls not using any form of hormone therapy). Controls were compared with treated women taking estrogens alone (n = 39), or taking estrogens in combination with a progestin (n = 25). Mean time on hormone therapy was approximately 5 years, with initiation of treatment in close proximity to the onset of menopause. Explicit memory was assessed with the California Verbal Learning Test (CVLT). Saliva was collected before (basal or resting sample) and after (post-test sample) completing a set of cognitive tasks. Cortisol was measured using a high-sensitivity radioimmunoassay. Treated women were found to have higher resting cortisol concentrations than controls matched for time of day. Basal cortisol was a modest predictor of learning and memory on the CVLT. Higher cortisol was associated with better recall and fewer memory errors, which is consistent with experimental studies examining explicit memory under small increases in circulating cortisol load. Potential cumulative effects on the central nervous system of sustained exposure to mildly increased cortisol in conjunction with the long-term use of oral estrogens are discussed in the context of aging and dementia.