Estrogen and stroke risk

November 3, 2009

Eighteen years ago this month the National Institutes of Health (NIH) announced that it would sponsor a landmark study to examine women and cardiovascular disease. Known as the Women's Health Initiative (WHI), the study enrolled more than 161,000 women. By 2004 however, the government had ended two arms of the study involving estrogen after researchers found it posed a small but detrimental risk for stroke to postmenopausal women taking the hormone. The findings caught many members of the scientific community by surprise as estrogen had previously been shown to protect the brain from stroke in animal models.

Stroke, also known as a brain attack, is America's third leading cause of death. It typically occurs when blood flow to the brain is blocked, usually due to a clogged artery. When a occurs, can result, especially in the area known as the hippocampus, thought to be the site for memory, memory loss, and learning. Despite the possible link between and stroke many women continue to take the hormone to manage their menopausal symptoms.

Does Estrogen Replacement Need to Occur Before Menopause to Protect the Brain?

Researchers at the Medical College of Georgia (MCG), along with collaborators at the North China Coal Medical University in Tangshan, China, and the University of Texas Health Sciences Center in San Antonio, have taken the understanding between the hormone and the risk, and advanced scientific understanding. Their new study, using animals, finds that (1) estrogen clearly and strongly protects the hippocampus after stroke, thereby reducing some aspects of stroke-related brain damage; (2) that the hippocampus region of the brain becomes hypersensitive after a stroke if it has gone without sufficient levels of estrogen for long periods of time (and this study is the first to observe this transformation); (3) that long periods of low estrogen makes the hippocampus insensitive to estrogen protective effects, though the tissues of the uterus retain their sensitivity to estrogen; and (4) estrogen significantly inhibits activation of a key membrane enzyme - NADPH oxidase, which produces reactive free radical molecules that cause brain damage - following stroke.

The study provides support for the theory that there may be a "critical period" for beneficial protective effect of estrogen on the brain - e.g. that of estrogen replacement may need to be initiated prior to or at the time of menopause if estrogen is to protect the brain. Additional studies will need to confirm the findings.

The study was conducted by Darrell W. Brann, Quan-Guang Zhang, Limor Raz and Dong Han of the Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta; Ratna Vadlamudi of the University of Texas Health Sciences Center in San Antonio, and Ruimin Wang and Fang Yang, of the Research Center for Molecular Biology, North China Coal Medical University, Tangshan. Dr. Brann presented an overview of the team's findings at the American Physiological Society (APS) conference Sex and Gender this summer. The study's findings have been accepted and been published in the November 4, 2009 online edition of the Journal of Neuroscience (http://www.jneurosci.org/). The article is entitled "Estrogen Attenuates Ischemic Oxidative damage via an ERα-Mediated Inhibition of NADPH Oxidase Activation."

Methodology and Findings

E2, or 17β-estradiol, is a specific form of estrogen. It is unclear how it is used to protect the brain in general or the hippocampus in particular. Rats whose ovaries had been removed were used for the study and received either placebo or 17β-estradiol after the ovaries were removed in an attempt to mimic the progression of estrogen loss during menopause.

The animals were randomly assigned to one of four groups. Group 1 experienced only sham surgery and no stroke or estrogen (sham). Group 2 was induced with stroke and immediately received a faux drug (placebo). Group 3 animals were treated with 17β-estradiol for one week after being ovariectomized and then stroke was induced. Group 4 rats received either estrogen or placebo ten weeks after being ovariectomized and one week later stroke was induced.

Samples were taken from the rats and examined. Statistical analyses were also performed. Afterwards the researchers found:

  • That since there was no stroke in group 1, there was little to no free radical production in the brain.

  • In group 2, there was a strong induction of the free radical superoxide, produced by the enzyme, NADPH oxidase in the hippocampus following stroke.

  • In Group 3, estrogen was found to strongly block the NADPH oxidase-induced production of superoxide, and it protected the brain and reduced oxidative damage to it.

  • In group 4 animals, which had been deprived of estrogen for a prolonged period similar to the situation that occurs after menopause, the protective effect of estrogen on the brain was completely lost. It no longer blocked NADPH oxidase activation and superoxide production, and no longer protected the brain.

  • In the long-term estrogen deprived animals, it was found that there was a significant loss in the hippocampus of one of the receptors for estrogen, thereby leading to the lost sensitivity to estrogen.

  • In addition, another region of the hippocampus, the CA3 region, which is normally resistant to stroke damage, became hypersensitive to damage by stroke in the animals that had been deprived of estrogen for an extended period.
Thus, the study demonstrated that a long period of estrogen deprivation led to a loss of estrogen's sensitivity and protective effects in the hippocampus, and that some parts of the hippocampus that are normally resistant to stroke damage, lose this resistance when deprived of estrogen for a prolonged period of time.

Conclusions

According to Dr. Brann, "Every study has potential limitations, including ours. Our studies were performed in animals and it is unclear if the results are applicable to humans. Further research is needed to address this issue." Nevertheless, said Brann, "The study provides support for the idea that there is a "critical period" for beneficial effect of estrogen upon the brain and provides insights to the mechanisms underlying this critical period." He added, "It suggests studies in humans should focus on replacing estrogen prior to or at the time of menopause to examine for potential beneficial effects upon the ."

Source: American Physiological Society (news : web)

Filter


Move the slider to adjust rank threshold, so that you can hide some of the comments.


Display comments: newest first

deatopmg
Nov 04, 2009

Rank: not rated yet
It appears that this revealing study was done w/ bio-identical hormones, not the un-natural, synthetic ones prescribed almost exclusively by the medical industry.
Rank 5 /5 (1 vote)
Relevant PhysicsForums posts
  • Is Everyday Technology Killing Us?
    createdFeb 08, 2012
  • Exercise and weight loss
    createdFeb 08, 2012
  • Why do we have head aches? Our brains can't feel anything.
    createdFeb 07, 2012
  • "The end of diseases" by David Agus, interview from Daily Show with Jon Stewart
    createdFeb 04, 2012
  • Oncolytic adenovirus
    createdFeb 04, 2012
  • Nutrition label stuffs and diets
    createdFeb 02, 2012
  • More from Physics Forums - Medical Sciences

More news stories

Starve a virus, feed a cure? Findings show how some cells protect themselves against HIV

A protein that protects some of our immune cells from the most common and virulent form of HIV works by starving the virus of the molecular building blocks that it needs to replicate, according to research published online ...

Medicine & Health / Research

created 3 hours ago | popularity 5 / 5 (1) | comments 0 | with audio podcast

Injured boomers beware: Know when to see doctor

(AP) -- It happened to nurse Jane Byron years after an in-line skating fall, business owner Haralee Weintraub while doing "men's" push-ups, and avid cyclist Gene Wilberg while lifting a heavy box.

Medicine & Health / Health

created 4 hours ago | popularity 5 / 5 (1) | comments 0

FDA-approved drug rapidly clears amyloid from the brain, reverses Alzheimer's symptoms in mice

Neuroscientists at Case Western Reserve University School of Medicine have made a dramatic breakthrough in their efforts to find a cure for Alzheimer's disease. The researchers' findings, published in the journal Science, show t ...

Medicine & Health / Neuroscience

created Feb 09, 2012 | popularity 4.9 / 5 (56) | comments 15 | with audio podcast

Green tea found to reduce disability in the elderly

(Medical Xpress) -- A lot of research has been done over the past several years looking into the health benefits of green tea. As a result, scientists have found that regular consumption of the beverage leads ...

Medicine & Health / Health

created Feb 07, 2012 | popularity 4.4 / 5 (15) | comments 10 | with audio podcast report

Teen school drop-outs three times as likely to be on benefits in later life

Teen school drop-outs are almost three times as likely to be on benefits in later life as their peers who complete their schooling, indicates research published online in the Journal of Epidemiology and Community Health.

Medicine & Health / Health

created Feb 06, 2012 | popularity not rated yet | comments 13


Scientists discover molecular secrets of 2,000-year-old Chinese herbal remedy

For roughly two thousand years, Chinese herbalists have treated Malaria using a root extract, commonly known as Chang Shan, from a type of hydrangea that grows in Tibet and Nepal. More recent studies suggest that halofuginone, ...

New method to examine batteries -- MRI from the inside

There is an ever-increasing need for advanced batteries for portable electronics, such as phones, cameras, and music players, but also to power electric vehicles and to facilitate the distribution and storage of energy derived ...

Google might launch Drive for cloud storage soon

(PhysOrg.com) -- Google's next big move, according to the Wall Street Journal, is a cloud storage service called Drive. Hardly first to the plate, Google is simply catching up to introducing its cloud reposi ...

Lab study raises questions over nano-particle impact

Tests involving chickens have raised questions about the impact on health from engineered nano-particles, the ultra-fine grains commonly used in drugs and processed foods, scientists said on Sunday.

A mitosis mystery solved: How chromosomes align perfectly in a dividing cell

Although the process of mitotic cell division has been studied intensely for more than 50 years, Whitehead Institute researchers have only now solved the mystery of how cells correctly align their chromosomes during symmetric ...

Researchers find extensive RNA editing in human transcriptome

In a new study published online in Nature Biotechnology, researchers from BGI, the world's largest genomics organization, reported the evidence of extensive RNA editing in a human cell line by analysis of RNA-seq data, demons ...