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Estrogen Is Involved in Stress Response

Findings Could Explain Why Depression Is More Common in Women
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WebMD Health News

Dec. 3, 2003 -- New research from Yale University may help explain why women are twice as likely as men to suffer from stress-related mental illnesses such as depression. Animal studies show that high levels of the female sex hormone estrogen affect the brain's ability to deal with stress.

Estrogen was found to amplify the stress response in areas of the brain most closely identified with depression and other stress-related mental illnesses. Researchers say the findings may one day lead to the development of treatments for depression that specifically target women.

"These findings suggest that there is a difference between men and women in how the prefrontal cortex responds to stress," says graduate student Rebecca M. Shansky, who was the study's lead researcher.

Estrogen Increases Stress Sensitivity

The Yale team exposed male and female rats to different levels of stress and then had the rats perform a short-term memory task designed to assess prefrontal cortex function. This region of the brain has been shown in previous brain imaging studies to be abnormal in depressed people. In the absence of stress, both the males and females performed the task equally well, and both sexes performed poorly when exposed to relatively high levels of stress.

Yet when levels of estrogen were high, female rats were impaired by lower levels of stress than male rats. During periods when this hormone was low, they responded similarly to male rats to stress.

"High estrogen levels made these animals more sensitive to the effects of stress," Shansky tells WebMD.

To further investigate estrogen's role in stress response, the investigators removed the ovaries from another group of female rats, and then implanted a time-released capsule containing either estrogen or placebo. When these rats performed a memory task, increased stress sensitivity was seen after estrogen replacement. The findings are reported in the December issue of the journal Molecular Psychiatry.

Depression and PTSD

For any woman who suffers from cycle-related depression or mood swings, the idea that estrogen plays a role in stress response may seem like old news. But Shansky says being able to pinpoint exactly how estrogen influences the brain's reaction to stress is new.

"It is important that people don't interpret this as evidence that women can't handle stress," she says. "This study didn't really address everyday stresses. It speaks much more to stress-related diseases like depression and posttraumatic stress disorder."

Estrogen and Memory

The Yale study is one of several indicating that sex hormones such as estrogen in women and testosterone in men have a more important role in brain function than previously thought.

Cornell University researcher Teresa Milner, PhD, and colleagues recently showed that estrogen helps regulate the brain's ability to learn and encode memories. Studies by other researchers show that testosterone may perform the same function in men.

"It is now clear that many cognitive functions are affected by (these hormones), and we are now trying to pinpoint where in the brain this is happening," Milner tells WebMD.

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