Impact of combined estradiol and norethindrone therapy on visuospatial working memory assessed by functional magnetic resonance imaging.

Author(s): Smith YR, Love T, Persad CC, Tkaczyk A, Nichols TE, Zubieta JK

Affiliation(s): Department of Obstetrics and Gynecology, School of Public Health, University of Michigan Health Systems, Women's Hospital, Ann Arbor, Michigan 48109-0276, USA. ysmith@umich.edu

Publication date & source: 2006-11, J Clin Endocrinol Metab., 91(11):4476-81. Epub 2006 Aug 15.

Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

CONTEXT: Hormones regulate neuronal function in brain regions critical to cognition; however, the cognitive effects of postmenopausal hormone therapy are controversial. OBJECTIVE: The goal was to evaluate the effect of postmenopausal hormone therapy on neural circuitry involved in spatial working memory. DESIGN: A randomized, double-blind, placebo-controlled crossover study was performed. SETTING: The study was performed in a tertiary care university medical center. PARTICIPANTS: Ten healthy postmenopausal women of average age 56.9 yr were recruited. INTERVENTIONS: Volunteers were randomized to the order they received hormone therapy (5 microg ethinyl estradiol and 1 mg norethindrone acetate). Subjects received hormone therapy or placebo for 4 wk, followed by a 1-month washout period with no medications, and then received the other treatment for 4 wk. At the end of each 4-wk treatment period, a functional magnetic resonance imaging study was performed using a nonverbal (spatial) working memory task, the Visual Delayed Matching to Sample task. MAIN OUTCOME MEASURE: The effects of hormone therapy on brain activation patterns were compared with placebo. RESULTS: Compared with the placebo condition, hormone therapy was associated with a more pronounced activation in the prefrontal cortex (BA 44 and 45), bilaterally (P < 0.001). CONCLUSIONS: Hormone therapy was associated with more effective activation of a brain region critical in primary visual working memory tasks. The data suggest a functional plasticity of memory systems in older women that can be altered by hormones.