Regular exercise may prevent the mental decline associated with the long-term use of hormone replacement therapy (HRT), preliminary research suggests.

In a study of 54 postmenopausal women, investigators found that long-term HRT use - more than 10 years - was linked with poorer scores on a standard test of mental acuity. However, physical fitness appeared to counter this effect, according to findings published in the journal Neurobiology of Aging.

While recent research in animals and humans has suggested that short-term estrogen replacement may help thwart age-related mental decline, long-term HRT use may have the opposite effect.

In the new study, researchers at the University of Illinois at Urbana-Champaign looked at whether women’s fitness levels made a difference in the brain effects of HRT.

Dr. Kirk I. Erickson and his colleagues collected information on HRT use and used MRI scans to measure tissue volume in several key brain areas. The women also took a standard test of memory and mental agility, as well as a treadmill test to gauge their cardiovascular fitness.

Overall, the researchers found that short-term HRT use - up to 10 years - was associated with greater brain tissue volume and better test scores. And higher fitness levels appeared to “augment” this benefit, they write.

Longer-term HRT use, in contrast, was linked to lower brain tissue volume and poorer test scores. However, physical fitness seemed to offset this effect, according to the researchers.

“It may be that a combination of HRT and exercise boosts both cognition and brain structure of older women,” study co-author Dr. Arthur F. Kramer said in a statement.

It’s not clear why exercise and short-term, but not long-range, HRT may be beneficial to the aging brain. Both estrogen and physical activity, the study authors note, stimulate a substance called brain-derived neurotropic factor, which is involved in the production of brain cells and blood vessels.

Whatever the reasons for the findings, Erickson and his colleagues conclude, they do demonstrate that brain atrophy “is not an inevitable consequence of aging,” and there may be several ways - such as exercise, a healthful diet or staying mentally active - that can slow or stop the process.

SOURCE: Neurobiology of Aging, online January 8, 2006.