A TONIC FOR THE MIND

By BY CLAUDIA WALLIS.

Long before it works its turbulent magic at puberty, long before we are even born, estrogen leaves its indelible mark on our mental functions. Not only does it help sculpt the brain during the earliest stages of development; it also continues to play a role in learning and memory throughout life. Subtle differences between the male and female brain can be traced to the influences of estrogen and testosterone in the womb. (While all fetuses are exposed to their mother's estrogen, male fetuses produce testosterone in their testes by the 12th week of gestation.) Particularly affected is the hypothalamus, a walnut-size structure located near the top of the brainstem that governs sexual development and sexual behavior and regulates temperature and water balance. Many scientists believe that such gender differences as the male facility with math, the female facility with language, girls' slightly superior hearing and skill at interpreting facial expressions are hardwired prenatally through the influence of the sex hormones.

Later these hormones play a housekeeping role in the growth and maintenance of brain cells in both sexes. (In boys some testosterone is converted to estrogen in the brain.) When estrogen is in short supply, memory and thought processes can suffer. Psychologist Barbara Sherwin at Montreal's McGill University has studied the effects of estrogen therapy on women who have had their ovaries removed and thus produce very little estrogen of their own. She found that women who were given injections of estrogen were better at learning and recalling pairs of words than those given a placebo. The effect is intriguingly specific; it involves verbal tasks (at which women tend to excel) but not visual memory.

Even the normal rise and fall of estrogen during a woman's menstrual cycle can affect mental performance. Young women do better on Sherwin's word-pair memory tests during the luteal phase of their cycle, when estrogen and progesterone levels are high, than during menstruation, when hormone levels are low. This doesn't mean women are less competent late in their cycles, says Sherwin; the changes are too minor "to have any real effect in the real world." Still, there is little doubt that the foggy forgetfulness that envelops some women as they approach menopause is a direct result of low estrogen. The fog generally lifts on its own, but hormone therapy can bring an almost instant break in the clouds.

Just how estrogen works in the brain remains obscure, though research by Bruce McEwen at Rockefeller University has shown that the hormone increases the number of connections between nerve cells in the hippocampus, a region that helps govern memory. Estrogen also increases the production of acetylcholine, a brain chemical that is abnormally low in Alzheimer's patients.

Dr. Howard Fillit, a geriatrician at New York City's Mount Sinai Medical Center, has conducted small-scale tests of estrogen with women who have mild to moderate Alzheimer's. Patients who did not know the month or year could recall them after just three weeks on daily doses of hormones. The women became more alert, ate and slept better, and showed improved social behavior. Fillit believes testosterone therapy may prove equally useful for male patients. Estrogen is not yet an approved therapy for Alzheimer's, but as the evidence builds, it is fast becoming one of the brightest hopes in a so far bleak field.

--By Claudia Wallis. Reported by Alice Park/New York

With reporting by Alice Park/New York