| Women
with Alzheimer’s disease who receive long-term estrogen replacement
may have worsened memory loss Postmenopausal women with Alzheimer's disease who undergo long-term estrogen replacement therapy may have increased memory loss, according to an article in the October issue of Behavioral Neuroscience. The researchers used female rats to study the effect of estrogen replacement therapy on memory because the conditions reproduced in the study are analogous to those of postmenopausal women with existing brain inflammation caused by a neurodegenerative illness like Alzheimer's disease or by head trauma who receive long-term estrogen replacement therapy. The American team taught 40 rats to perform a water maze task to look at the interaction of chronic neuroinflammation and excessive or inadequate estrogen. Both conditions (neuroinflammation and hormonal disturbance) are likely to precede the onset of symptoms associated with Alzheimer's disease. As part of the experiment, some of the rats were given bilateral oopherectomy to mimic menopause. Aged rats do not undergo the ovarian failure seen in ovariectomized rats. However, female rats that have undergone oopherectomy experience both the ovarian failure and the alterations in gene expression within the hypothalamus that appear in women in menopause. The researchers found that removal of the rats' ovaries was not enough to impair performance in the water maze task. However, the introduction of either sustained estrogen replacement therapy or chronic brain inflammation did impair memory performance in the rats in the surgery group. Furthermore, the combined occurrence of both conditions (sustained estrogen replacement therapy and longer-term brain inflammation) significantly worsened cognitive performance beyond that produced by either condition alone. "A therapy designed to mimic the natural cycle of hormone fluctuation may provide a more effective therapy to slow the progression of Alzheimer's disease in postmenopausal women," according to the researchers. They added that their findings were echoed by an article published in 2000 in the Journal of the American Medical Association that was based on a long-term, placebo-controlled study on the effects of estrogen replacement therapy on cognitive function in a large group of women with mild to moderate Alzheimer's disease. The effects of estrogen replacement therapy were initially beneficial, but the performance of women receiving sustained therapy declined over time more than that of women who received placebo treatment. "When considered together, the results of this and other clinical trials suggest a pattern of beneficial effects on cognitive function after relatively short-term estrogen replacement therapy; however, this beneficial effect is attenuated, and possibly reversed, after much longer treatment regimens," said the authors of the current study. "Although a comparison between
humans and rodents must be made with caution, it is interesting
that continuous long-term estrogen therapy immediately after oopherectomy
in the present study parallels the detrimental cognitive effect
seen in postmenopausal Alzheimer's disease women who receive continuous,
long-term estrogen replacement therapy decades after the onset of
menopause." |