Cumulative estrogen exposure and prospective memory in older women




Hesson, Jacqueline Barbara

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With the average female life expectancy in Canada currently at 82 years, women are now spending approximately one-third of their lives in a hypoestrogenic state. Numerous studies from the basic sciences have shown that estrogen is neuroprotective in a variety of ways. The findings from the clinical studies of the effects of estrogen replacement on cognition in postmenopausal women are more inconsistent, though current research suggests that the timing of initiation of estrogen replacement relative to menopause is a major contributing factor to the discrepant findings in this literature. Reproductive and biological variables that affect levels of endogenous estrogen throughout a woman's lifespan may also influence cognitive function later in life as well as modify a woman's response to exogenous estrogen. The present study looked at the effects of cumulative estrogen exposure on the performance of a measure of prospective memory in a group of older postmenopausal women. Cumulative estrogen exposure was estimated using a mathematical index that included variables known to influence estrogen levels across the life span such as age at menarche and menopause, parity, duration of breastfeeding and estrogen replacement therapy, body mass index and time since menopause. Prospective memory is memory for future intentions and it was chosen because of its relevance for independent function and possible utility as an early indicator of dementia. Imaging studies link prospective memory to the prefrontal cortex, an area of the brain that is known to be influenced by estrogen so it was hypothesized that women with higher levels of cumulative estrogen exposure would perform better on a measure of prospective memory than women with lower levels of endogenous estrogen. Measures of verbal memory were also included in the study for comparative purposes as verbal memory is the cognitive function reported most consistently in the previous literature to be affected by postmenopausal estrogen replacement use. The results of the multivariate analyses indicated a significant positive correlation between prospective memory scores and cumulative estrogen exposure but only when women who had initiated estrogen replacement more than five years after menopause were excluded from the analysis. The significant positive correlation between cumulative estrogen exposure and prospective memory performance remained significant when only women who had never used estrogen were included in the analysis. No relationships were observed between levels of cumulative estrogen exposure and performance on measures of verbal memory. While the study was limited by the fact that it was observational in nature and the sample size was small, the results are consistent with recent findings from the hormone literature, in that they suggest that the timing of hormone replacement as well as the influence of variables that affect endogenous estrogen levels over a woman's lifespan need to be considered when studying relationships between cognitive performance and estrogen. In addition, the finding that performance on a measure of prospective memory but not performance on a measure of verbal memory was associated with levels of cumulative estrogen exposure adds further support to the theory that the frontal cortex may be especially sensitive to estrogen.



Hypoestrogenic, postmenopausal