Estrogen: for men and women, balm for the brain

Let’s get a couple of things straight first about estrogen, the so-called “female hormone.” First, it influences a lot more than just what’s going on “down there”: it’s produced by the brain, of course, and brain scientists are increasingly studying estrogen as a “neuromodulator,” a chemical with powerful effects on the brain as well as the reproductive system.

Second, it’s not just females who have estrogen, need it and suffer with its loss. Males do too, as a recent study involving the humble songbird makes clear.

A group of studies presented in San Diego this week at the annual meeting of the Society for Neuroscience suggest that estrogen is indeed powerful:

It may buffer women of childbearing age from the toxic effects of stress on her baby as well as herself, one study found. Shoring up declining estrogen levels in middle-aged women seems to prevent decline in cognitive skills -- including remembering things when under stress -- two other studies suggest.

And in male as well as female songbirds (and, neuroscientists would have us believe, in humans too), estrogen levels in the brain spike at the sound of socially-meaningful things -- say, the cry of a baby. In male songbirds, estrogen in the brain rises at such cues as well. At such moments, estrogen causes neurons in the brain’s sensory cortex to fire faster.

At the health sciences campus of the University of Southern California in Los Angeles, 42 postmenopausal women were asked to submerge their hands in icy water for three minutes. Twenty minutes later, the women were put through a dizzying test of working memory and multitasking skill, remembering lists of words while also reading sentences and judging whether they were grammatically correct or not.

For almost five years, the women had been taking either estrogen replacement therapy or a placebo. The study authors knew that the hippocampus -- a key node in the brain’s memory circuit -- is highly sensitive to estrogen, and that stress routinely causes memory impairments. They wondered whether the women who had gotten hormone replacement would weather the double-whammy of icy waters and short-term memory challenge better than those who had not.

The women with the highest levels of estrogen in their blood not only remembered more words and judged the grammar of sentences more accurately: they responded with less stress than those with lower levels of estrogen, as measured by their levels of the stress hormone cortisol.

At Vanderbilt School of Medicine, Dr. Paul Newhouse and his colleagues investigated a more roundabout way of increasing estrogen’s cognitive effects in women after menopause: with the breast cancer drug tamoxifen. Although tamoxifen blocks estrogen’s action in the breast -- thus preventing recurrence in women who’ve been treated for breast cancer -- the drug is believed to increase estrogen’s clout in the brain.

In all, 21 participants took tamoxifen for three months, and a placebo for another three months. At the end of each trial period, the women were presented with a different kind of mental challenge: undergoing tests of mental skills while taking one of two drugs that mimics the chemical effects on the brain of aging, including difficulty in forming memories: the motion-sickness drug scopolamine and an early drug for high blood pressure, mecamylamine.

For the women who took it, tamoxifen appeared to buffer the cognitive effects of the two other drugs, and they performed better in tests of attention, verbal memory and spatial navigation. And its benefits were greatest for women who were found in genetic assays to have a genetic variation that put them at higher risk for developing Alzheimer’s disease.