Thursday, March 20, 2008

Doctors Use Estrogen to Treat Memory Loss in Older Women

Not that wicked "pill" again! The one that medical researchers do their best to discredit

Gayatri Devi was a neurologist and psychiatrist specializing in memory disorders when a patient's case changed her career. The 52-year Brazilian woman, once a dynamo, had become forgetful and disoriented. Dr. Devi and her colleagues diagnosed early Alzheimer's disease and prescribed a standard AD drug. As an afterthought, Dr. Devi added estrogen, having seen research suggesting it might slow the dreaded disease.

Six months later, the woman returned and insisted she was cured. "I didn't believe it, but we tested her and her symptoms had resolved, thanks to the estrogen," says Dr. Devi. "That was the beginning of my journey." In the 10 years since, Dr. Devi has treated several hundred patients for menopause-related memory loss in her New York City practice. Many are professional women who find they can't summon up words or lose track of what they were doing. Some are afraid to tell anyone, some have been dismissed as simply stressed. And some are still years away from menopause; the hormonal ups and down are often more pronounced in "perimenopause," which can start as much as seven years earlier. "They're terrified they are developing Alzheimer's disease," says Dr. Devi. "But the majority of them do respond to estrogen."

Other doctors who specialize in menopause say such cognitive problems are just as common as hot flashes and often more worrisome. "Women have been telling me this for 25 years," says Elizabeth Lee Vliet, a women's health physician with offices in Tucson, Ariz., and Dallas, Tex., who notes that her patients often speak of feeling "fuzzy-headed." She takes detailed blood tests and typically prescribes 17-beta estradiol, an FDA-approved estrogen replacement. "They come back a couple weeks later and say 'It was like someone turned a lightbulb on my brain! I can think again!' "

The phenomenon isn't surprising considering that there are estrogen receptors throughout the brain, particularly in the areas that govern learning, memory and mood. Estrogen also stimulates the growth of dendritic spines that enable nerve cells to communicate, and increases the level of neurotransmitters, the brain's chemical messengers In addition, estrogen helps regulate glucose, inflammation and antioxidants in the brain. Neuroimaging studies have shown that when estrogen declines, there is markedly less cerebral blood flow and activity.

Men's brains function differently. A 2005 study from the University of California at Irvine found that men rely much more heavily on gray matter, the information-processing centers in the brain, while women utilize more white matter, which provides networks between the processing centers. In short, women's brains make more connections. "Women remember word for word what somebody said yesterday, or last year," says Dr. Devi. But men's brains also require estrogen, which is converted from testosterone. In fact, because men continue to make testosterone all their lives, a 72-year old man typically has more estrogen than a 72-year old woman.

Many studies have confirmed that declining estrogen affects visual and verbal memory, language and other cognitive skills. Barbara Sherwin, a professor of psychology and ob/gyn at McGill University in Canada, has shown that women who had their ovaries removed surgically and were given estradiol -- the estrogen replacement that is the same as women lose -- scored significantly higher on tests of short- and long-term memory and verbal memory than women who had received placebos. In a study published in the Lancet in 1996, researchers at Columbia University found that elderly women who took estrogen replacement were 50% less likely to develop Alzheimer's disease later in life.

Other studies have found contradictory results -- most prominently, the Women's Health Initiative Memory Study (WHIMS), part of the big government hormone trial. It reported in 2004 that women taking estrogen plus progestin had a higher risk of dementia than those who took a placebo.

But just as with other arms of the WHI, the memory study enrolled women who were well past menopause when they started taking hormones. The subjects were aged 65 to 79. Many experts now believe there is a critical period of about 10 years after menopause when estrogen can protect women's brains, while beginning to take hormones later can be harmful. (That same critical period seems to exist for heart attack and stroke as well; women in the main WHI who started estrogen within 10 years of menopause had a decreased risk of heart attack and of death in general while women who started at older ages saw an increased risk.)

In addition, the WHIMS trial used Premarin, conjugated equine estrogen, which some experts say doesn't act on the brain as well as 17-beta estradiol. WHIMS also used a synthetic progestin that has been shown to negate some of the effects of estrogen. (Indeed, the WHIMS group that was given estrogen alone showed no increase for either Alzheimer's disease or mild cognitive impairment.) Finally, the trial used a measure of cognitive function known as the "modified mini-mental state examination" that isn't sensitive enough to assess any beneficial effects that estrogen might have had on verbal or working memory.

Many experts think the WHIMS findings needlessly frightened some women away from estrogen who might have benefited from it. Some who found the symptoms so unpleasant they've resumed. Says Dr. Devi "They say they can live with a possible future risk but that acting like an idiot today is a real problem."

There are still many unanswered questions -- including how long women should stay on estrogen. One study found that taking it for two to three years still provided protection for brain function 15 years later. Indeed, not all women suffer memory loss or fuzzy thinking at menopause, just like post-partum depression and pre-menstrual syndrome don't affect all women. "Some women are very sensitive to this decrease and some aren't," says Dr. Sherwin.

For women who are sensitive, HRT can be a lifeline. Lupe Iniguez, a tax attorney in Phoenix and mother of four found her estrogen levels so depleted in 2002 that she says "I couldn't think. I couldn't remember names of clients. I couldn't focus on documents. I resigned from every board and started to make arrangements to retire on disability." But after Dr. Vliet put her on an estradiol patch, Ms. Iniguez says, "I'm practicing full throttle again. I got my life back."


Gene therapy advancing

A new way of turning genes on and off, pioneered by a Nobel prize-winning British scientist, is promising to transform treatment of conditions such as HIV/Aids, heart disease and diabetes. The technique, devised by Sir Aaron Klug, of the Laboratory of Molecular Biology in Cambridge, allows scientists to act with unprecedented precision against genes that affect a wide range of diseases, switching them on or off permanently.

The first drugs designed to target the genes have begun clinical trials in the United States on patients with arterial disease and diabetes-induced nerve damage. A third trial, for HIV, is due to begin within months. If they are successful, scientists predict that the technique could change the way many diseases are treated, making genetic therapies a routine part of medicine for the first time. In some cases, the method will be used to switch off rogue genes that promote conditions such as heart failure or cancer. In others, it will help to activate genes that protect against nerve damage or encourage blood vessel growth.

In treating HIV, the aim is to modify T-cells from patients' immune systems so that they become immune to infection with the virus. This would leave them with some working T-cells with which to fight off other infections, which are the chief cause of Aids deaths. The technique relies on a natural process by which the activity of genes is raised or lowered by proteins called transcription factors.

In 1985 Sir Aaron discovered a new class of proteins that mimic this function and can recognise specific stretches of DNA and bind to them, boosting the activity of genes or damping them down. He named them zinc-finger proteins, after the metal that holds them together and the way in which they grasp DNA. Sangamo BioSciences, a company in California, has already developed several drugs based on the principle. A zinc-finger protein specific to a gene is loaded with an enzyme called a nuclease, which will bind to the gene and turn it on or off. Sir Aaron told The Times: "We are taking nature's own method of regulating gene activity and exploiting it for our own purposes. We can use this technique to change the function of a single gene permanently. "The beauty of zinc-finger nucleases lies in their simplicity. Where other methods are long, arduous and often messy, it is relatively easy to switch off genes using this method. The zinc-finger design allows us to target a single gene, while the nuclease disrupts the gene." Details of the technique are published today in the journal Proceedings of the National Academy of Sciences.

The most advanced of Sangamo's drugs uses a zinc-finger nuclease to treat diabetic neuropathy, a common complication of diabetes that causes nerve damage and pain. The drug binds to a gene called VEGF-A, which is known to protect the nervous system, and switches it on to prevent nerve damage. Phase 2 trials of the drug are under way. The same gene is also being targeted to treat peripheral arterial disease which causes blocked arteries in the limbs. A zinc-finger drug that has started safety trials aims to stimulate VEGF-A activity, which can promote the growth of new arteries. In the longer term, a similar approach might be used to grow new blood vessels in the heart, Sir Aaron said.

Sangamo is applying for regulatory permission to start testing a zinc-finger nuclease on HIV patients as well as developing drugs to treat glioblastoma, a type of brain cancer, and single-gene disorders such as sickle-cell anaemia.



Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

9). And how odd it is that we never hear of the huge American study which showed that women who eat lots of veggies have an INCREASED risk of stomach cancer? So the official recommendation to eat five lots of veggies every day might just be creating lots of cancer for the future! It's as plausible (i.e. not very) as all the other dietary "wisdom" we read about fat etc.

10). And will "this generation of Western children be the first in history to lead shorter lives than their parents did"? This is another anti-fat scare that emanates from a much-cited editorial in a prominent medical journal that said so. Yet this editorial offered no statistical basis for its opinion -- an opinion that flies directly in the face of the available evidence.

Even statistical correlations far stronger than anything found in medical research may disappear if more data is used. A remarkable example from Sociology:
"The modern literature on hate crimes began with a remarkable 1933 book by Arthur Raper titled The Tragedy of Lynching. Raper assembled data on the number of lynchings each year in the South and on the price of an acre's yield of cotton. He calculated the correlation coefficient between the two series at -0.532. In other words, when the economy was doing well, the number of lynchings was lower.... In 2001, Donald Green, Laurence McFalls, and Jennifer Smith published a paper that demolished the alleged connection between economic conditions and lynchings in Raper's data. Raper had the misfortune of stopping his analysis in 1929. After the Great Depression hit, the price of cotton plummeted and economic conditions deteriorated, yet lynchings continued to fall. The correlation disappeared altogether when more years of data were added."
So we must be sure to base our conclusions on ALL the data. But in medical research, data selectivity and the "overlooking" of discordant research findings is epidemic.

"What we should be doing is monitoring children from birth so we can detect any deviations from the norm at an early stage and action can be taken". Who said that? Joe Stalin? Adolf Hitler? Orwell's "Big Brother"? The Spanish Inquisition? Generalissimo Francisco Franco Bahamonde? None of those. It was Dr Colin Waine, chairman of Britain's National Obesity Forum. What a fine fellow!


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