TY - JOUR
T1 - Potential age-dependent effects of estrogen on neural injury
AU - Leon, Rachel L.
AU - Huber, Jason D.
AU - Rosen, Charles L.
N1 - Funding Information:
Supported by National Institutes of Health, National Institutes of Neurological Disorders and Stroke grant RO1 061954 (J.D.H). Activase was provided by Genentech (San Francisco, California).
PY - 2011/6
Y1 - 2011/6
N2 - In 2000, approximately 10 million women were receiving hormone replacement therapy (HRT) for alleviation of menopausal symptoms. A number of prior animal studies suggested that HRT may be neuroprotective and cardioprotective. Then, in 2003, reports from the Women's Health Initiative (WHI) indicated that longterm estrogen/progestin supplementation led to increased incidence of stroke. A second branch of the WHI in women with prior hysterectomy found an even stronger correlation between estrogen supplementation alone and stroke incidence. Follow-up analyses of the data, as well as data from other smaller clinical trials, have also demonstrated increased stroke severity in women receiving HRT or estrogen alone. This review examines the studies indicating that estrogen is neuroprotectant in animal models and explores potential reasons why this may not be true in postmenopausal women. Specifically, age-related differences in estrogen receptors and estrogenic actions in the brain are discussed, with the conclusion that animal models of disease must closely mimic human disease to produce clinically relevant results.
AB - In 2000, approximately 10 million women were receiving hormone replacement therapy (HRT) for alleviation of menopausal symptoms. A number of prior animal studies suggested that HRT may be neuroprotective and cardioprotective. Then, in 2003, reports from the Women's Health Initiative (WHI) indicated that longterm estrogen/progestin supplementation led to increased incidence of stroke. A second branch of the WHI in women with prior hysterectomy found an even stronger correlation between estrogen supplementation alone and stroke incidence. Follow-up analyses of the data, as well as data from other smaller clinical trials, have also demonstrated increased stroke severity in women receiving HRT or estrogen alone. This review examines the studies indicating that estrogen is neuroprotectant in animal models and explores potential reasons why this may not be true in postmenopausal women. Specifically, age-related differences in estrogen receptors and estrogenic actions in the brain are discussed, with the conclusion that animal models of disease must closely mimic human disease to produce clinically relevant results.
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U2 - 10.1016/j.ajpath.2011.01.057
DO - 10.1016/j.ajpath.2011.01.057
M3 - Review article
C2 - 21641373
AN - SCOPUS:79959475783
SN - 0002-9440
VL - 178
SP - 2450
EP - 2460
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -