Effects of long-term, low-dose sex hormone replacement therapy on hippocampus and cognition of postmenopausal women of different apoE genotypes.
OBJECTIVE
To study the effects of long-term, low-dose sex hormone replacement therapy (HRT) on the volume and biochemical changes of the hippocampus in postmenopausal women carrying apolipoprotein E (apoE) gene epsilon3 or epsilon4.


METHODS
Eighty-three postmenopausal women who had used a low dose of HRT for over 4 years were selected as the HRT group, and 99 postmenopausal women with matched age and education were enrolled as the control group. ApoE alleles were analyzed by PCR. Magnetic resonance imaging was performed to determine the volume of the brain hippocampus. Proton magnetic resonance spectroscopy was used to detect the biochemical changes in the anterior cingulate cortex and hippocampus in apoE epsilon4 and epsilon3 carriers. Six common cognitive tests were used to make an overall evaluation of cognitive function.


RESULTS
Analysis with the apoE epsilon4 carriers showed that the volume of the hippocampus of the control group were significantly lower than those of the HRT group. The biochemical analysis showed that there was an increase of N-acetylaspartate (NAA)/total creatine (tCr) and a decrease of myoinositol (mI)/tCr in the hippocampus of apoE epsilon4 carriers in the HRT group, compared with the control group. For the apoE epsilon3 carriers, the least squares means (LSMEAN) of the HRT group was higher than that of the control group.


CONCLUSIONS
This study showed that long-term, low dose HRT might be beneficial for reducing the risk of AD development in vulnerable postmenopausal women. Meanwhile, HRT could increase the LSMEAN of apoE epsilon3 carriers.
Yue
Yun
Y
School of Basic Medicine, Peking Union Medical College and Institute of Basic Medical Science, Chinese Academy of Medical Sciences, Beijing, China.
Hu
Ling
L
Tian
Qin-jie
QJ
Jiang
Jing-mei
JM
Dong
Yi-long
YL
Jin
Zheng-yu
ZY
Cheng
Yu-hang
YH
Hong
Xia
X
Ge
Qin-sheng
QS
Zuo
Ping-ping
PP
D000368:Aged; D000544:Alzheimer Disease / Q000517:prevention & control; D001057:Apolipoproteins E / Q000235:genetics*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D003071:Cognition; D003404:Creatinine / Q000032:analysis; D003430:Cross-Sectional Studies; D015914:Estrogen Replacement Therapy; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D007294:Inositol / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D017698:Postmenopause; D012189:Retrospective Studies
D001057:Apolipoproteins E; D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate; D003404:Creatinine