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November 16, 2006

Hormone therapy may improve the trip down memory lane

Treatment with hormones shows promise in helping visual memory of postmenopausal women, U-M researchers find

ANN ARBOR, MI – Many women experience declines in their memory during and after menopause, a change thought to be due, in part, to the rapid hormonal changes they weather during that time.

Yolanda R. Smith, M.D.Now, research from the University of Michigan Health System suggests that hormone therapy might help women retain certain memory functions. In a study in the new issue of The Journal of Clinical Endocrinology & Metabolism, they report that a group of postmenopausal women showed more brain activity during a visual memory test than did women who were not taking the hormone therapy.

The 10 postmenopausal women in the study, ages 50-60, were given hormone therapy or a placebo for four weeks, followed by a month with no medications, and then four weeks of the other treatment. Their brain activation was measured as they were shown a complex grid of 81 squares, with 40 of them darkened to form a pattern.

Participants were asked to find the matching image from a choice of two, with the new set of images presented after varying time periods (one to four seconds). During the time that the two images were shown, participants were asked to choose the one that matched the initial grid by pressing one of two buttons on an MRI (magnetic resonance imaging)-compatible response pad.

Those who were taking combined estrogen-progestin hormone therapy showed significantly increased activity in the prefrontal cortex, a region of the brain that is critical in memory tasks, compared with those on placebo (a pill with no medicinal value). The researchers used images from functional MRI, or fMRI, to compare the participants’ brain activity.

“Our findings suggest that even relatively short periods of hormone therapy have effects on the memory systems that may be of benefit to some women during the perimenopausal transition or early postmenopause,” says lead author Yolanda R. Smith, M.D., associate professor in the Department of Obstetrics and Gynecology at the U-M Medical School.

“Other studies have indicated that long-term hormone therapy is not beneficial for the prevention of chronic illnesses,” Smith says. “But our study indicates that the effects of short-term hormone therapy on brain circuitry and function warrant further study.”

Jon-Kar Zubieta, M.D., Ph.D.The role of estrogen in maintaining brain function is of great significance as the population ages and the incidence of dementia increases, says senior author Jon-Kar Zubieta, M.D., Ph.D., associate professor of psychiatry and radiology at the U-M Medical School and associate research scientist at U-M’s Molecular & Behavioral Neuroscience Institute (MBNI).

Zubieta notes that working memory – that is, a limited-capacity storage system that allows the brain to actively maintain and manipulate information that is critical for conducting many daily activities over short time periods – has been demonstrated to be less efficient in older adults. This decline has been linked with changes in the prefrontal cortex.

“Our finding of increased activation in the prefrontal cortex in older women using hormone therapy is important and suggestive of potential therapies that need to be explored further,” he says. “Eventually, this could lead to new options for women as they enter a time when memory problems typically develop.”

The researchers also point out that there have been shown to be risks with hormone replacement therapy. Information is available at www.nhlbi.nih.gov/health/women/pht_facts.pdf.

In addition to Smith and Zubieta, other authors were Tiffany Love, B.S., of the U-M Department of Psychiatry and MBNI; Carol C. Persad, Ph.D., of the Department of Psychiatry; Anne Tkaczyk, M.S., of the Department of Obstetrics and Gynecology; and Thomas E. Nichols, Ph.D., of the Department of Biostatistics at the U-M School of Public Health.

The research was supported in part by a grant from the National Center for Research Resources and an investigator-initiated grant from Pfizer Pharmaceuticals Group. Smith received an investigator-initiated grant from Pfizer Pharmaceuticals, Nichols has consulted for GlaxoSmithKline Inc., and Zubieta has received lecture fees from GlaxoSmith Kline Inc., Eli Lilly and Co., and Forest Laboratories.

Citation: The Journal of Clinical Endocrinology & Metabolism, “Impact of Combined Estradiol and Norethindrone Therapy on Visuospatial Working Memory Assessed by Functional Magnetic Resonance Imaging,” first published ahead of print Aug. 15, 2006.

Written by Katie Gazella

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