Long-term estrogen replacement therapy may make memory loss worse in postmenopausal women with Alzheimer's disease, according to researchers at the University of Arizona.

Researchers used 40 female rats to test the effect of hormone replacement therapy on memory loss. The findings are applicable to humans because the conditions reproduced in the study are similar to that of postmenopausal women who have brain inflammation caused by a neurodegenerative illness such as Alzheimer's disease.

The rats performed a water maze task that showed the interaction between the presence of chronic neuroinflammation and having too much or not enough estrogen, which are conditions that are likely to precede the onset of symptoms linked with Alzheimer's disease. Some of the rats had their ovaries removed to mimic the changes seen in postmenopausal women.

Researchers found that the removal of the rats' ovaries was not enough to impair performance in the water maze task. However, adding sustained estrogen replacement therapy or chronic brain inflammation did impair memory performance in the rats with their ovaries removed.

The combination of sustained estrogen replacement therapy and longer term brain inflammation significantly worsened memory performance beyond what was 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," the researchers reported in Behavioral Neurosciences.

Their findings followed a report in the Journal of the American Medical Association last year that involved a long term, placebo-controlled study that looked at the effects of estrogen replacement therapy on cognitive function in large groups of women with mild to moderate Alzheimer's disease.

The effects of estrogen replacement therapy were beneficial, but the cognitive performance of the women receiving sustained estrogen replacement therapy declined more than that of those taking a placebo.

"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 possible reversed, after much longer treatment regimens," the researchers concluded.

"Although a comparison between humans and rodents must be made with caution, it is interesting that continuous long-term estrogen therapy immediately after ovariectomy 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," the reported.

Other sources: American Psychological Association