Testosterone Converts to Estrogen to Ward Off Depression

Recommended by Dr. Michael White, Updated on October 19th, 2020
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By Traci Pedersen Associate News Editor Reviewed by John M. Grohol, Psy.D. on March 30, 2015 ~ 1 min read

In order to protect males with low-testosterone from the effects of anxiety and depression, much of the testosterone in his brain must first be converted into estrogen, according to new findings by a researcher at Florida State University College of Medicine.

Mohamed Kabbaj, a professor of biomedical sciences received a six-year grant from the National Institute of Mental Health to investigate the ways in which anxiety affects the sexes differently.

Kabbaj already knew that testosterone tends to protect males from depression and anxiety, just as estrogen and progesterone do in females. He also knew that most testosterone was converted into estrogen in the brain. What he didnt know, however, was that those anxiety- and depression-inhibiting actions couldnt take effect until the testosterone was first converted to estrogen.

There is an enzyme in the brain that mediates the conversion of testosterone into estrogen, Kabbaj said. We inhibited that enzyme in a specific brain area implicated in the regulation of mood. And when you do that, you lose the antidepressant effect of testosterone. So the conversion is very important.

His research targeted the hippocampus area of the brain, where testosterone acts through whats known as the MAPK pathway to deliver its antidepressant and anti-anxiety effects.

But we have to be careful about that pathway, Kabbaj said, because its also implicated in cellular growth and cancer. Therefore, were looking for other pathways that dont have these effects. Its complicated. Nothing is ever simple, but well get there.

Women are 70 percent more likely than men to suffer from depression during their lifetime, according to National Institute of Mental Health. So far, the link between testosterone conversion and anxiety/depression has been detected only in laboratory animals. But Kabbaj says the results are potentially promising for humans as well.

Maybe in the future, when we are trying to develop an antidepressant that works in low-testosterone males, we can target some of the mechanisms by which testosterone acts, since it has numerous side effects, he said.

Testosterone acts on many receptors and pathways in the brain, so the challenge is to develop a drug that delivers only the effect you want.

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Testosterone Converts to Estrogen to Ward Off Depression

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