Male Brains Need Estrogen for Good Memory

From the WebMD Archives

Nov. 7, 2000 -- The male brain works much differently than the female brain -- but both need the female sex hormone estrogen for good memory. And like women, men who take hormone replacement therapy can improve their verbal memory, according to the early results of studies reported at this week's meeting of the Society for Neuroscience.

"Estrogen is important for memory in both men and women, but there are gender differences as to which aspects of memory improve in men and women," Sanjay Asthana, MD, tells WebMD. "Estrogen in women improves verbal memory, visual memory, and attention. In men estrogen improves only verbal memory."

Men didn't actually take estrogen in the study by Asthana's team at the University of Washington in Seattle and the VA Puget Sound Healthcare System in Tacoma. Instead, like other men who receive hormone replacement therapy, they took testosterone. But part of testosterone is broken down by the body into the active form of estrogen known as estradiol.

Could this extra estradiol improve memory in men, as it does in women who take estrogen-based hormone replacement therapy? To find out, the researchers gave some of the men a second drug that blocked the breakdown of testosterone into estradiol.

"We found that testosterone alone can improve an aspect of memory known as spatial memory -- the kind of memory needed to drive, get dressed, use a knife and fork -- what you need to learn to navigate three-dimensional space," Asthana says. "But men with both testosterone and estrogen had better verbal memory."

Testosterone replacement therapy is highly controversial. Most doctors prescribe it only for men whose levels of the male sex hormone are abnormally low for their age. But some doctors think it might be a good idea to raise aging men's testosterone levels to match those of younger men. The major drawback is that testosterone makes prostate cancers grow much faster -- so men with enlarged prostates or with previous prostate cancer must not take the hormone.

Asthana thinks that new estrogen-like drugs that lack sex-hormone effects such as breast enlargement might be useful to preserve memory in aging men. He says he is planning to test this theory in human trials.

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Even if estrogen helps men's memories, it doesn't mean their brains work the same way women's brains do.

"We are all very much aware that males and females can react differently to the same experience," Tracey Jo Shors, PhD, tells WebMD. "We do that because our brains are different. I'm not sure how much it's appreciated how different they are."

Shors and co-workers at Rutgers University taught rats to perform new tricks. They found that female rats learn much better than male rats at the time of their normal reproductive cycle when their estrogen levels were high. But all this changed for up to two days after the rats went through a 30-minute period of high stress.

"Males and females were exposed to the very same experience, but they responded in opposite directions," Shors says. "Females do much more poorly after stress, while males do much better in terms of new learning."

When they looked at the animals' brains, the researchers saw a dramatic difference between the males and the females. After stress the male brains were awash with stress hormones, while the female brains had extremely high levels of estrogen -- much higher than those occurring during the normal reproductive cycle. Brain cells in the males sprouted new nerve connections, while female brain cells actually lost connections.

"Males and females exposed to [the] same experience respond in opposite directions -- and so do their brains," Shors says. "This is biology, not some social pressure to behave as a male or female -- after all, these are rats."

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