Estrogen Aids Brain Activity, Tests Find

Standard doses of the sex hormone estrogen strengthen brain activity in older, post-menopausal women, Yale University researchers said Tuesday, offering the best evidence yet that the commonly prescribed hormone alters the neural circuits involved in human memory.

By testing the kind of working memory involved in everyday verbal and visual tasks, the researchers quickly detected significant differences in neural activity between women who were taking the hormone and those who were not.

The hormone appeared to restore a surprising level of neural flexibility and malleability more common among young people than among women who in many instances may be approaching retirement age.

“These data suggest that estrogen affects brain organization in post-menopausal women,” said Yale neuroscientist Sally E. Shaywitz, who led the research team, which reported the findings today in the Journal of the American Medical Assn.

Neurologist Katharine Yaffe at UC San Francisco, who studies estrogen and cognition, said, “These are fascinating results . . . very exciting.”

Normally, the production of estrogen drops dramatically after women reach menopause. Researchers have established that estrogen replacement therapy confers several physical benefits on older women, such as protection against the potentially crippling bone loss of osteoporosis and against heart disease.

But its effect on mental functions remains more controversial. While some researchers have turned up no link between estrogen and intellectual abilities in older women, others say they have found evidence it may boost short-term memory, improve reaction times or counter depression in post-menopausal women.

Indeed, some researchers are hopeful estrogen may help alleviate some effects of Alzheimer’s disease and the more normal ill effects of aging.

To study estrogen’s effects on the human brain directly, Shaywitz and her Yale colleagues for the first time used a high-speed medical scanning technique called functional magnetic resonance imaging (fMRI). The imaging technique allows researchers to watch how patterns of blood flow in the brain change in fractions of a second as mental activity brings different neural circuits into play.

In all, Shaywitz and her colleagues imaged the brains of 46 women between the ages of 33 and 61 as they memorized and then recalled nonsense words or letters in a foreign alphabet. For three weeks before the test, the women, who all had undergone menopause, took a form of estrogen called Premarin--the most commonly prescribed drug in the United States--or a placebo.

“When we compared the brain activation patterns on and off estrogen, we found that there are significant differences,” Shaywitz said. The response of the brain to memory tasks was simply stronger when more estrogen was present. “The brains [on estrogen] acted like the brains of younger women.

“That is very exciting because it shows that you can actually alter brain activation patterns,” Shaywitz said. “We generally associate such [neural] flexibility with younger children and not with older people, especially post-menopausal women.”

Because of the way the imaging test was designed, the women did not show any noticeable difference in their conscious ability to recall the words, only at the more subtle level of cellular brain function. The researchers believe, however, that the brain activity does reflect improved memory.

The study buttresses previous psychological studies and animal experiments attesting to the influence of estrogen on memory.

But the new research also offers important evidence that the normal aging human brain is far more flexible than researchers once thought.

“What this study suggests is that what estrogen can do is rewire the central nervous system,” said Dr. Stanley Birge, a professor of geriatrics and gerontology at the Washington University School of Medicine in St. Louis. “Perhaps even in the 70- or 80-year-old individual we have the potential” for this kind of mental renewal.

Even so, the researchers cautioned, any woman considering estrogen replacement therapy needs to weigh any benefit against potential side effects, which include an increased risk of breast cancer and endometrial cancer.