Gayatri Devi, a neurologist and psychiatrist, was working with a team of other memory specialists in 1997 when a patient's case changed her career. The patient, a 52-year-old Brazilian woman, had become forgetful and disoriented. The team 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 dread disease.

Six months later, the woman 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 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," Dr. Devi says. "But the majority of them do respond to estrogen."

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.

Many studies have confirmed that declining estrogen affects 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 same type of estrogen produced by the ovaries - scored significantly higher on tests of 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 percent less likely to develop Alzheimer's disease later in life.

Other studies 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 ages 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. (Women in the main WHI who started estrogen within 10 years of menopause also 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.

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. "Some women are very sensitive to this decrease and some aren't," Dr. Sherwin says.

For women who are sensitive, HRT can be a lifeline. Lupe Iniguez, a tax attorney in Phoenix and mother of four, says she found her estrogen levels so depleted in 2002 that "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 her doctor, Elizabeth Lee Vliet in Tucson, put her on an estradiol patch, Ms. Iniguez says, "I'm practicing full throttle again. I got my life back."

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Estrogen Connection

For more information on estrogen and memory, see:

- "Estrogen, Memory & Meno- pause" by Gayatri Devi, M.D.

- "It's My Ovaries, Stupid" by Elizabeth Lee Vliet, M.D.

- http://www.nymemory.org: Dr. Devi's New York Memory and Health Aging Services

- http://www.Herplace.com: Dr. Vliet's informational site

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Last updated: 04/17/2008 - 09:26 AM