Impact of combined estradiol and norethindrone therapy on visuospatial working memory assessed by functional magnetic resonance imaging
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Updated: Aug 6, 2026
Functional Magnetic Resonance Imaging (fMRI) of the Visual Cortex with Wide-View Retinotopic Stimulation
Published on: December 8, 2023
Yolanda R Smith1, Tiffany Love, Carol C Persad
1Department 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
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.