Long-Term HRT Worsens Memory

A Few Years of Estrogen in Early Menopause May Be Best

From the WebMD Archives

Oct. 28, 2002 -- For older women who have Alzheimer's, a decade of estrogen replacement therapy (ERT) may mean worse memory loss.

New research involving rats shows that instead of helping prevent onset of dementia, ERT actually made learning worse, reports Gary L. Wenk, PhD, professor of neurology and psychiatry at the University of Arizona Medical Center in Tucson.

His study appears in this month's Behavioral Neuroscience.

Alzheimer's disease is the most common cause of dementia and memory loss in older adults. Older women are especially at risk for developing Alzheimer's; family history and some environmental toxins seem to play a role. But some brain changes are part of the natural aging process, Wenk tells WebMD.

"Inflammation in the brain is just something that happens as you get older," he says. In fact, scientists are beginning to pay closer attention to this brain inflammation, to better understand Alzheimer's and other brain diseases, Wenk says.

In their study, Wenk and colleagues looked at the link between menopause, Alzheimer's, and estrogen.

The study involved 40 female rats. The researchers induced brain inflammation similar to Alzheimer's disease in half of the rats. These rats also had their ovaries removed to mimic menopause. The researchers then gave the rats ERT and looked at its effect on learning.

Then, they tried "teaching" the rats to go through a maze.

The findings: Those rats that had received ERT -- and that had brain inflammation -- did worse in the maze test later on.

It was a surprise to Wenk. "We expected the animals to get better with chronic estrogen therapy," he tells WebMD. "We initially thought it would be very positive, very beneficial, that it would show estrogen would improve cognitive [learning] function in the female mice with brain inflammation."

Earlier studies had shown that women taking ERT in menopause were less likely have Alzheimer's, he says.

However, one study -- published midway through Wenk's study -- showed that when women with early-onset Alzheimer's were taking ERT, their memory got worse.

"That was the same thing we were seeing," he tells WebMD. When he performed additional rat studies, he saw the same thing, time after time.

The rats' experience equals the effects of women taking "chronic estrogen" -- estrogen in the bloodstream on a 24-hour, seven-day-a-week basis, for about a decade.

Bottom line: Once the Alzheimer's process has begun, ERT is not going to benefit brain function, he says. "Chronic estrogen is not a good thing."

The study may point toward beneficial effects from short-term ERT -- perhaps meaning that women should take estrogen pills two or three days every month. "It would be more like a natural estrogen surge that would have a protective effect," he says.

Wenk's study confirms what other researchers have shown, says George Bartzokis, MD, director of UCLA's memory disorders clinic.

"Once you already have Alzheimer's disease, HRT does not seem to be beneficial," he tells WebMD. "However, what [Wenk and colleagues] are not really addressing -- and what most people do not know -- is that Alzheimer's disease develops over a period of 30 years. That means that a large percentage of the population has the process going on in their 60s and even 50s."

Wenk's study shows that estrogen has more value as a "neuroprotectant" -- a brain protector, he says. "When women take it earlier -- when they're 50 -- that's when we see the protective effect, like taking a vaccine for the flu."