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


METHODS
A randomized, double-blind, placebo-controlled crossover study was performed.


METHODS
The study was performed in a tertiary care university medical center.


METHODS
Ten healthy postmenopausal women of average age 56.9 yr were recruited.


METHODS
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.


METHODS
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.
Smith
Yolanda R
YR
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
Love
Tiffany
T
Persad
Carol C
CC
Tkaczyk
Anne
A
Nichols
Thomas E
TE
Zubieta
Jon-Kar
JK
D001921:Brain / Q000000981:diagnostic imaging; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000379:methods; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008568:Memory / Q000187:drug effects*; D008875:Middle Aged; D008954:Models, Biological; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077563:Norethindrone Acetate; D010919:Placebos; D017698:Postmenopause / Q000187:drug effects; D011859:Radiography; D013028:Space Perception / Q000187:drug effects*; D014796:Visual Perception / Q000187:drug effects*
D010919:Placebos; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone