Hormone Therapy Linked to Brain Shrinkage, But Not Lesions

Earlier studies showed that estrogen with or without added progestin increased the risk for developing dementia and cognitive decline, or difficulty with thinking skills and memory in women age 65 and older.

These new studies aimed to look at how the hormones might affect memory and thinking skills. The studies involved participants of the Women’s Health Initiative hormone therapy clinical trials who also agreed to participate in a substudy called the Women’s Health Initiative Memory Study. These studies were stopped earlier than planned when researchers found that the hormone therapy increased health risks and failed to prevent heart disease.

Researchers took MRI brain scans of 1,400 women ages 71 to 89 one to four years after the Women’s Health Initiative hormone studies ended. They found women who had taken estrogen with or without progestin had smaller brain volumes in two areas of the brain than the women who had taken a placebo. Brain volume was 2.37 cubic centimeters lower in the frontal lobe in the women taking estrogen and .10 cubic centimeters lower in the hippocampus. Both areas are involved in thinking and memory skills, and loss of volume in the hippocampus is a risk factor for dementia.

“These effects were most apparent in women who may already have had some memory problems before they started taking hormones,” said study author Susan Resnick, PhD, of the National Institute on Aging in Baltimore, MD. “This suggests that estrogen may adversely affect thinking skills among women whose brains may already be beginning a neurodegenerative disease process.”

In the second study, researchers found that hormone therapy was not linked to an increase in volumes of small vascular lesions in the brain or “silent strokes” that are often the first sign of cerebrovascular disease. “This was not what we expected to find,” said study author Laura H. Coker, PhD, of Wake Forest University Health Sciences in Winston-Salem, NC. Coker said the negative effects of hormone therapy on cognitive skills may not be related primarily to vascular disease but to neurodegeneration, which is supported by the first study’s findings of brain atrophy.

The Women’s Health Initiative, a major 15-year research program designed to address the most frequent causes of death, disability and poor quality of life in postmenopausal women, is funded by the National Heart, Lung, and Blood Institute. The memory study was also funded in part by Wyeth Pharmaceuticals, Inc.

The American Academy of Neurology, an association of more than 21,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as multiple sclerosis, restless legs syndrome, Alzheimer’s disease, narcolepsy, and stroke.