Estrogen Deprivation Increases Stroke Risk

In aging rats prolonged estrogen deprivation reduces the number of brain receptors and increases the risk of stroke, finds study.

However, the damage is forestalled if estrogen replacement begins shortly after hormone levels drop, according to a study.

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"This is further evidence of a critical window for estrogen therapy, either right before or right after menopause," said Dr. Darrell W. Brann, Chief of GHSU's Developmental Neurobiology Program and the study's corresponding author.

The surprising results of the much-publicized Women's Health Initiative - a 12-year study of 161,808 women ages 50-79 - found hormone therapy generally increased rather than decreased stroke risk as well as other health problems.

After long periods without estrogen, researchers found that an enzyme called CHIP - carboxyl terminus of Hsc70 interacting protein - increased binding with estrogen receptor alpha, a major brain receptor for neuroprotection. While CHIP levels remain unchanged, the increased binding results in about half the receptors getting hauled to the cell's proteosome to be chopped up and degraded.

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When researchers later treated the aged rats with estrogen, they found what the Women's Health Initiative showed: increased mortality.

Next steps included estrogen-treating those rats where CHIP-related destruction is blocked to see if salvaged receptors will respond and looking at the process in other areas of the brain.

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"We think the estrogen receptor decrease is why the sensitivity decreases," said Brann, who also is Associate Director of GHSU's Institute of Molecular Medicine and Genetics.

"If the hormone is gone long enough it is logical there would be decreased sensitivity as normal feedback between the receptor and hormone is reduced," Brann added.

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The study has been published in the journal Proceedings of the National Academy of Sciences.

Source-ANI