Testosterone needs estrogen’s help to inhibit depression
In popular culture, the phrase “battle of the sexes” seems to pit the male hormone (testosterone) against the female (estrogen). Now a Florida State University College of Medicine researcher has documented a way in which the two hormones work together to protect low-testosterone males from the effects of anxiety and depression.
Specifically, the testosterone must first be converted into estrogen. That’s the latest discovery from the lab of biomedical sciences Professor Mohamed Kabbaj. With a six-year grant from the National Institute of Mental Health, he is investigating the ways in which anxiety affects the sexes differently.
Women are 70 percent more likely than men to experience depression during their lifetime, according to the NIMH. It also reports that “major depressive disorder” affects more than 20 million U.S. adults each year.
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 come up with a drug that provides only the effect you want.
Borderline Testosterone Levels Linked to Higher Rates of Depression in Men
Men with borderline testosterone levels have higher rates of depression and depressive symptoms than the general population, according to a new study.
“Over half of men referred for borderline testosterone levels have depression,” said Michael S. Irwig, M.D., F.A.C.E., associate professor of medicine and director of the Center for Andrology in the Division of Endocrinology at George Washington University in Washington, D.C.
“This study found that men seeking management for borderline testosterone have a very high rate of depression, depressive symptoms, obesity and physical inactivity. Clinicians need to be aware of the clinical characteristics of this sample population and manage their comorbidities, such as depression and obesity.”
For their study, Irwig and his colleagues studied 200 men between 20 and 77 years of age whose testosterone levels were borderline (between 200 and 350 nanograms per deciliter).
The researchers collected the men’s demographic information, medical histories, medication use, and signs and symptoms of hypogonadism.
“A number of treatments are available for depression, but the drugs are not effective in all patients and the side effects can be serious, especially on the heart,” said biomedical sciences Professor Pradeep Bhide, director of the College of Medicine’s Center for Brain Repair. “Therefore, there is an urgent need for safer and more efficacious drugs to treat depression. Dr. Kabbaj’s research is offering new insights into the causes of depression and the role of hormones in this disorder. Such insights are critical for the development of new drugs and diagnostic tests.”
Kabbaj’s latest paper was published in Biological Psychiatry.
Low Testosterone and Depression
Though not entirely understood, the link between testosterone and a wide variety of health problems is one of the most interesting discoveries in men’s health. Testosterone is a steroid hormone that humans produce naturally. It is generally thought of as a male hormone, although it is actually produced by both men and women. Men do, however, produce an average of 20 times more testosterone than do women and use it up at a much higher rate.
Testosterone is the most important hormone for male sexual development. It plays a big role in the growth of primary reproductive organs, as well as the development of so-called secondary sexual characteristics, such as body hair and muscle mass. In addition, testosterone seems to have a strong connection to overall male health, although the exact nature of this connection is still something of a mystery.
Cause or Effect
Research has begun to identify a number of serious medical conditions that have some connection to a man’s testosterone levels. Low testosterone is a condition that affects about 30 percent of men 55 years of age and older. Men suffering from diabetes, high blood pressure or obesity were all more likely to have abnormally low testosterone levels. The reverse is also true: men with low testosterone levels are more likely to have or develop diabetes or obesity. However, the way in which these conditions are connected to low testosterone is something researchers are still working on.
One possibility is that low testosterone levels somehow increase a man’s likelihood of developing one of these or several other major health problems. An equally likely possibility is that conditions such as diabetes and obesity, or just poor health in general, may result in the lowering of an individual’s testosterone levels. There are other possibilities as well, including the chance that both low testosterone and the conditions that have been linked to it are all caused by some other factor or factors.
He already knew that testosterone had a protective effect on males, just as estrogen and progesterone do on females. He also knew that most testosterone was converted into estrogen in the brain. What he didn’t know was that those anxiety- and depression-inhibiting effects couldn’t be produced unless 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 lab targeted the hippocampus area of the brain, where testosterone acts through what’s known as the MAPK pathway to induce its antidepressant and anti-anxiety effects.
“But we have to be careful about that pathway,” Kabbaj said, “because it’s also implicated in cellular growth and cancer. Therefore, we’re looking for other pathways that don’t have these effects. It’s complicated. Nothing is ever simple, but we’ll get there.”
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Story Source:
Florida State University. “Testosterone needs estrogen’s help to inhibit depression.” ScienceDaily. ScienceDaily, 26 March 2015