Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks.
BACKGROUND
Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of estrogen on verbal memory in postmenopausal women.


OBJECTIVE
To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks.


METHODS
Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998.


METHODS
Community volunteers tested in a hospital setting.


METHODS
Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years).


METHODS
Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments.


METHODS
Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory.


RESULTS
Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks.


CONCLUSIONS
Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.
Shaywitz
S E
SE
Department of Pediatrics, School of Medicine, Yale University, New Haven, Conn 06510-8064, USA. Sally.Shaywitz@yale.edu
Shaywitz
B A
BA
Pugh
K R
KR
Fulbright
R K
RK
Skudlarski
P
P
Mencl
W E
WE
Constable
R T
RT
Naftolin
F
F
Palter
S F
SF
Marchione
K E
KE
Katz
L
L
Shankweiler
D P
DP
Fletcher
J M
JM
Lacadie
C
C
Keltz
M
M
Gore
J C
JC
D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008568:Memory / Q000187:drug effects*; D008875:Middle Aged; D009483:Neuropsychological Tests; D017698:Postmenopause
D004966:Estrogens, Conjugated (USP)