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publicado em 04/04/2013 às 11h45:00
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Removal of the ovaries before menopause makes brain more vulnerable to stroke

Research shows that treatment with low doses of estrogen after the surgery appears to reduce stroke risk

 
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Removing the ovaries before menopause, appears to leave more of the brain vulnerable to stroke and increase the risk of Alzheimer' s disease, researchers report.

Low doses of estrogen started right after surgery appear to reduce this vulnerability in an area of the brain that typically is not super-sensitive to stress, said Dr. Darrell Brann, Associate Director of the Institute of Molecular Medicine and Genetics at the Medical College of Georgia at Georgia Regents University.

This robust treatment response supports the " critical window" hypothesis of beginning low-dose estrogen replacement therapy right after ovaries are removed in younger women and continuing it until age 51, the median age of onset for menopause, Brann said.

Women who abruptly and prematurely lose estrogen from surgical menopause have a two-fold increase in cognitive decline and dementia.

" This is what the clinical studies indicate and our animal studies looking at the underlying mechanisms back this up," said Brann, corresponding author of the study in the journal Brain. " We wanted to find out why that is occurring. We suspect it' s due to the premature loss of estrogen."

In an effort to mimic what occurs in women, Brann and his colleagues looked at rats 10 weeks after removal of their estrogen-producing ovaries that were either immediately started on low-dose estrogen therapy, started therapy 10 weeks later or never given estrogen.

When the researchers caused a stroke-like event in the brain' s hippocampus, a center of learning and memory, they found the rodents treated late or not at all experienced more brain damage, specifically to a region of the hippocampus called CA3 that is normally stroke-resistant.

To make matters worse, untreated or late-treated rats also began an abnormal, robust production of Alzheimer' s disease-related proteins in the CA3 region, even becoming hypersensitive to one of the most toxic of the beta amyloid proteins that are a hallmark of Alzheimer' s.

Both problems appear associated with the increased production of free radicals in the brain. In fact, when the researchers blocked the excessive production, heightened stroke sensitivity and brain cell death in the CA3 region were reduced.

Interestingly the brain' s increased sensitivity to stressors such as inadequate oxygen was gender specific, Brann said. Removing testes in male rats, didn' t affect stroke size or damage.

Although exactly how it works is unknown, estrogen appears to help protect younger females from problems such as stroke and heart attack. Their risks of the maladies increase after menopause to about the same as males. Follow up studies are needed to see if estrogen therapy also reduces sensitivity to the beta amyloid protein in the CA3 region, as they expect, Brann noted.

Brann earlier showed that prolonged estrogen deprivation in aging rats dramatically reduces the number of brain receptors for the hormone as well as its ability to prevent strokes. Damage was forestalled if estrogen replacement was started shortly after hormone levels drop, according to the 2011 study in the journal Proceedings of the National Academy of Sciences.

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. Critics said one problem with the study was that many of the women, like Brann' s aged rats, had gone years without hormone replacement, bolstering the case that timing is everything.

Source: Georgias Health Sciences Univ
   Palavras-chave:   Removal of the ovaries    Surgical menopause    Stroke    Estrogen    Georgia Regents University    Darrell Brann   
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