Higher estrogen levels are not associated with larger hippocampi and better memory performance.
BACKGROUND
Estrogens may prevent cognitive decline and Alzheimer disease. Animal study findings have shown beneficial effects of estrogen on the brain, particularly on the hippocampus, a structure related to memory performance and early Alzheimer disease.


OBJECTIVE
To investigate whether higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes on magnetic resonance imaging and better memory performance.


METHODS
Cross-sectional analysis within the Rotterdam Scan Study, a population-based study in the Netherlands of elderly subjects who do not have dementia.


METHODS
Two hundred ten women and 202 men, aged 60 to 90 years, with plasma levels of total estradiol and, in part, 162 women and 149 men also with levels of bioavailable and free estradiol.


METHODS
Hippocampal volumes on magnetic resonance imaging and memory performance (delayed recall).


RESULTS
Women with higher total estradiol levels had smaller hippocampal volumes and poorer memory performance -0.29 mL (95% confidence interval, -0.57 to -0.00) and -0.4 (95% confidence interval, -1.3 to 0.5) fewer words in delayed recall testing for the highest tertile compared with the lowest tertile. Similar inverse associations were found among bioavailable and free estradiol levels, hippocampal volumes, and memory. In men, no association was observed between estradiol levels and hippocampal volume, but a trend was found for higher levels of total estradiol to be associated with poorer memory performance.


CONCLUSIONS
Our data do not support the hypothesis that higher levels of endogenous estradiol in older women and men are associated with larger hippocampal volumes and better memory performance.
den Heijer
Tom
T
Department of Epidemiology, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Geerlings
Mirjam I
MI
Hofman
Albert
A
de Jong
Frank H
FH
Launer
Lenore J
LJ
Pols
Huibert A P
HA
Breteler
Monique M B
MM
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D004958:Estradiol / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology* / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008569:Memory Disorders / Q000503:physiopathology*; D008875:Middle Aged
D004958:Estradiol