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Counting the Days

June 10, 2011
by Anne Pinckard
image of a paper cutout of people holding hands

How estrogen changes the way we think

Any married man knows better than to blame a woman’s mood on her menstrual cycle. He also knows better than to tell his wife that her hormones are making her irrational. Now a new study suggests that the menstrual cycle may in fact affect a woman’s cognitive ability, but not in the way you might think. Whether she is more or less clear-headed depends on her unique physiology, according to Berkeley neuroscientists Emily Jacobs, Ph.D. ’10, and Mark D’Esposito. Theirs is the first study to investigate exactly how estrogen alters the brain’s neurochemistry to hamper or enhance mental performance.

Previous studies measuring estrogen’s influence on cognition concluded that the hormone’s effect was “inconsistent,” according to Jacobs, who led the Berkeley study as a graduate student. “But if you dug a little more you would see that, actually, half the women were improving significantly when their estrogen levels were high, while the other half were impaired.”

The key lay in understanding how the hormone interacts with dopamine, a neurotransmitter active in the brain’s frontal lobe and responsible for “working memory”—such as remembering a phone number until you can jot it down. Estrogen, which spikes right before ovulation, enhances dopamine’s action, which has the same effect as increasing the amount of dopamine in our brains. But it turns out that just enough is required for optimal function—too much or too little can actually hamper our thinking abilities. Jacobs and D’Esposito tested for two gene variants that determined a woman’s baseline level of dopamine. Those who had low levels performed simple mental tasks more accurately right before ovulation, while those who had normally higher levels did worse at that time of the month but generally better at other times.

It’s a finding that is both tantalizing and frustrating, say the authors, because it calls attention to a deeper issue: the woeful lack of research on female subjects, whether human or lab animal. Jacobs quoted a recent Berkeley study that found in 80 percent of biological disciplines, research performed on mammals in 2009 focused primarily on males. “This paper is representative of that [finding],” said Jacobs. “It’s one example of how we would have just overlooked estrogen’s importance in the frontal lobe if we were only using males.” In practical terms, a drug such as Ritalin, which is used to treat ADHD by increasing dopamine levels, could have the opposite of its intended effect on a woman depending on her genetics and at different times of her cycle.

This study should not be interpreted to mean that these monthly fluctuations make women inferior to men. “Those kinds of extrapolations are completely unfounded in these data,” said Jacobs. Estrogen is only one of many influencing factors, including stress, that trigger dopamine release in both men and women. Furthermore, these differences—about 5 to 10 percentage points in memory accuracy—average out, she said, adding, “The estrogen boost could be to our advantage as much as it can be detrimental.”

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