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Testosterone-triggered brain-cell death behind ''roid rage'
Scripps Howard News Service


September 27, 2006

In a new finding that appears to confirm observations of "'roid rage" in steroid users, Yale University researchers report that high levels of testosterone can result in a catastrophic loss of brain cells.

Taking large doses of androgens, or steroids, is known to cause hyper-excitability, a highly aggressive nature and suicidal tendencies. Such behavioral changes could be evidence of altered brain-cell function caused by the steroids, said Barbara Ehrlich, senior author of the study published Wednesday in the Journal of Biological Chemistry. She is a professor of pharmacology and physiology at Yale's School of Medicine.




Her team worked with brain cells cultured in a lab setting, rather than with human subjects. However, Ehrlich said the results clearly demonstrate that cells die after being treated with elevated levels of testosterone for even six to 12 hours.

"We can show that when you have high levels of steroids, you have high testosterone and that can destroy the nerve cells. We know that when you lose brain cells, you lose function," Ehrlich said.

The process of brain-cell self-destruction is much the same as in those with Alzheimer's disease, the researcher said.

Yet other research has shown that boosting testosterone in older men whose levels of the male sex hormone naturally plummet actually helps protect brain function and memory.

"Too little testosterone is bad, too much is bad, but the right amount is perfect," Ehrlich said.

Of course, studies have also shown that taking estrogen supplements can help preserve brain function in older women. So the Yale team also tested whether super-doses of that hormone were detrimental to brain cells. They weren't.

"We were surprised, but it actually looks like estrogen is neuroprotective. If anything, there is less cell death in the presence of estrogen," Ehrlich said.

Although women also produce testosterone, men in their prime produce 20 times more of the hormone, and it serves a number of functions in regulating cell development and growth.

Its role in stimulating muscle-mass growth is why steroids have been used and abused by athletes in recent years. But their sustained use can cause side effects that include cancer, jaundice, high blood pressure, severe acne, tremors and changes in cholesterol levels that increase the risk of stroke and heart disease.

Psychiatric effects of the drugs may not be entirely due to the destruction of brain cells, however. There's evidence that steroids have some "feel-good" effect that contributes to a sense of invincibility when ingested. But because athletes tend to take them in on-off cycles to maximize their effects, the euphoria is often replaced with feelings of depression.

It's not clear from the study whether the cell damage from testosterone is uniform across the brain, or, as some experts suspect, hits regions that involve rational decision-making and emotional response especially hard.

Nonetheless, Ehrlich said the findings underscore the risks of steroid supplements.

"Next time a muscle-bound guy in a sports car cuts you off on the highway, don't get mad, just take a deep breath and realize that it might not be his fault," she observed.


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