Research has shown that estrogen increases older women's risk of developing dementia and cognitive decline. How estrogen does that, though, has been a matter of debate. But a study published online in Neurology suggests that the hormone may do this by shrinking women's brains.

A team of scientists at Wake Forest University, in Winston-Salem, N.C., found that participants receiving estrogen therapy were 75 percent more likely to develop dementia than a placebo group. That finding, published in the Journal of the American Medical Association (Vol. 289, No. 20), ran counter to many people's assumptions that estrogen therapy might slow cognitive decline, says Mark Espeland, PhD, a professor of public health sciences at the university's Baptist Medical Center.

"It was surprising to quite a few people," he says.

Espeland's team suspected that estrogen made older women's brains more susceptible to small strokes that usually go unnoticed. They began an MRI study to look for the strokes' telltale brain tissue damage.

They found no evidence of strokes, but they did see something peculiar: Compared with a placebo group, the estrogen-treated women's brains were slightly smaller in volume, especially in the frontal lobe and hippocampus. The frontal lobes in the estrogen-treated women had about 2.4 cubic centimeters (about a 10th of a cubic inch) less volume, about the size of a pencil eraser.

Espeland says it's unclear why estrogen would make a brain shrink, but he and his research team have launched a second study that might shine further light on the connection.

Meanwhile, estrogen remains the treatment of choice for menopause symptoms in women around age 50 because studies haven't found similar risks for that age group, Espeland says. That suggests a "window of opportunity," he adds, after which estrogen's risks might outweigh its benefits—though it's unclear how long that window might last.

—M. Price