Estradiol and progesterone associated changes in event-related potentials in young and older women

Abstract

Levels of the gonadal steroids estradiol and progesterone fluctuate during the menstrual cycle in young women and in response to hormone replacement therapy in postmenopausal women. Measuring the performance of women over the menstrual cycle with cognitive tests, it has been reported that gonadal steroids modulate cognitive skills with known sex differences (e.g. verbal fluency and spatial skills). Studies using event-related potentials, reported inconsistent results even though hormone associated changes in the perception and processing of emotional stimuli have been observed. With regard to effects of hormone-replacement therapy (HRT) on ERPs few double-blind, placebo-controlled studies with healthy elderly women have been published yet. We therefore conducted two studies aimed at evaluating changes in ERPs due to changing sex hormone concentrations over the menstrual cycle (study I) or as the result of hormonal treatment (study II). In the first study we tested changes of the ERPs across the menstrual cycle (menses, follicular phase, luteal phase) in young women. ERPs were measured with a vigilance-paradigm, oddball active-paradigm and the dichotic listening task. During the luteal phase there was a diminished orienting-response as well as an enhanced Slow Wave. Additionally, there was a longer N2-latency during the follicular and luteal phase in comparison to the menses. These results suggest a diminished initial attention to new stimuli and a delayed cognitive processing of relevant stimuli during the luteal phase, which also need more effortful late processing to be correctly identified. To test whether similar changes in ERPs occur after treatment with gonadal steroids (estradiol or estradiol plus progesterone versus placebo) we tested 51 menopausal women with the same ERP paradigms at three time points (baseline, 4 weeks of treatment, 24 weeks of treatment). No hormone induced differences in ERPs were observed. Result of these two studies suggest an altered responsiveness of the aged brain to gonadal steroid hormones.