HRT Shrinks the Brain

MONDAY Jan. 12, 2009 -- Two studies looking at the same group of women found that while hormone therapy is linked with brain shrinkage, it does not seem to be associated with early signs of cerebrovascular disease.

This suggests that hormone therapy's effect on brain volume, not its effect on the brain lesions that indicate "silent strokes," is the mechanism by which hormones increase the risk for dementia in women over 65.

"These are a nice companion to cognitive studies reported earlier. This is now neuroradiological evidence that, together, suggest that the effect [of hormones] may be more degeneration than vascular," said Miriam Weber, an assistant professor of physical medicine and rehabilitation and of neurology at the University of Rochester Medical Center.

These papers, both published in the Jan. 13 issue of Neurology, are the latest in a parade of analyses resulting from the hormone therapy arm of the landmark, government-sponsored Women's Health Initiative study.

Previous results included an increased risk of stroke and cerebrovascular disease in women over 65 taking hormone replacement therapy (HRT). Another offshoot of the WHI, the WHI Memory Study, found an increased risk of dementia and memory problems in this group of women.

Both papers set out to understand the mechanisms behind this increased risk for dementia in women taking conjugated equine estrogens (either estrogen alone or estrogen plus progestin).

In the primary paper, researchers analyzed brain scans on about 1,400 women in the WHI Memory Study, who had been on hormone therapy for about four to six years.

They found no relationship between vascular lesions in the brain or an increased risk of dementia.

"The main message is that women over 65 years of age who took CEE-based hormone therapy [either estrogen alone or estrogen plus progestin] through the WHI clinical trials and who agreed to have an MRI scan did not experience increases in brain lesion volume," said study author Laura H. Coker, an assistant professor of public health sciences at Wake Forest University School of Medicine in Winston-Salem, N.C.

The second paper, after analyzing MRI scans from the same group of people (now aged 71 to 89), found shrinkages in both the hippocampus and frontal lobe regions of the brain, which are critically involved in memory and cognitive function.

"Much to our surprise, we found a small but significant decrease in the hippocampal and frontal volumes, and a nonsignificant trend towards reduced total brain volume in women who had been randomized to hormone therapy," reported Susan M. Resnick, lead author of the second paper and a senior investigator with the Intramural Research Program at the U.S. National Institute on Aging. "The negative effects were most evident in women who already may have had some memory problems before using hormone therapy. . . so it suggests that hormone therapy may be accelerating processes that have already begun."

The most pronounced effect was seen in women with more brain lesions. "In a very healthy brain, the hormone therapy did not appear to have an adverse effect, but in women who were already having some problems, the hormone therapy did have an adverse effect," Resnick said.

In the WHI trial, hormones were given to 65-year-old women when, in real life, they are often given to much younger women, which may be a harbinger of good news.

"The encouraging thing is that younger women are much less likely to have vulnerable brains," Resnick explained.

Indeed, preliminary research presented earlier this year by the same team did find that women who start hormone therapy before they turn 65 could actually cut their risk of developing Alzheimer's or another dementia.

But Resnick cautioned, "these findings don't impact the current recommendations which are to use hormone therapy for treatment of menopausal symptoms for the shortest time at the lowest possible dose."

More information

Visit the U.S. National Heart, Lung, and Blood Institute for more on HRT use.

Posted: January 2009


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