Testosterone needs estrogen's help to inhibit depression (with commentary)

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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.
“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.
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.”
The co-authors of the Biological Psychiatry paper are (or previously were) affiliated with the College of Medicine: Nicole Carrier, Ph.D. alumna; Samantha Saland, graduate student; Florian Duclot, research faculty; Huan He, volunteer worker; and Roger Mercer, director, Translational Sciences Laboratory.

Source: http://www.defymedical.com/resource...ne-needs-estrogens-help-to-inhibit-depression




Article Commentary by J Bruce


Men and women on testosterone replacement therapy who previously suffered from low testosterone and depression already understand the positive effect that testosterone has on their mood. A study led by Rupert Lanzenberger from the Vienna Medical University Department of Psychiatry and Psychotherapy has demonstrated for the first time worldwide that testosterone increases the number of serotonin transporters (proteins) in the human brain. Serotonin is a neurotransmitter that plays an important role in maintaining positive mood and emotional well-being. There are many more studies which demonstrate the relationship between the sex hormone testosterone, depression, and positive mood. Maintaining adequate levels of testosterone is shown to reduce the occurrence of depression. The presentation titled “Testosterone needs Estrogen's help to inhibit Depression “by Professor Mohamed Kabbaj interestingly shows that both estrogen and testosterone work together to alleviate depression and anxiety. In both men and women, some testosterone converts to estrogen. In men, this is the primary source of estrogen. In women, estrogen is also produced in the ovaries. The article indicates that the actual conversion of testosterone to estrogen in the brain is necessary for anti-depressant and anti-anxiety effects. This research will hopefully help patients suffering from depression obtain better access to hormone testing and proper treatments when certain hormones are found to be too low.
The only statement I do not agree with is regarding the “need” to synthesize a drug which acts like testosterone due to the fear of “numerous side effects” associated with testosterone. Of course those of us who read the latest evidence know that the “numerous side effects” result from improper prescribing of testosterone and the lack of proper monitoring. Testosterone replacement therapy correctly administered and monitored by an experienced doctor has very low risk and long term health benefits. Why take a hormone already identical to what the body produces and alter it to produce a drug? I believe the efforts would be better spent educating more doctors on how to properly monitor testosterone replacement therapy after diagnosing low testosterone. Although this study is done on men, we know the effects are equally beneficial in women. Article excerpt: “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.”
Referenced: http://www.defymedical.com/resource...nd-antidepressants-brain-sthash-rfp69hrv-dpuf

"...the male sex hormone testosterone also affects our mood and emotions, as well as our libido -- and in a positive way."
 
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Defy Medical TRT clinic doctor
personally I've never suffered from depression, but I believe men are less likely to talk about their depression compared to women. There was a time that I thought depression was just BS, after having close friends suffer from it and commit suicide, I now know it is a real.
 
Bruce - Is he basically saying anti depressants work better on men with higher testosterone because they generally have a higher E2 conversion which is needed to allow anti depressants to work better? I had horrible anxiety and depression while on test, my E2 was at the high end of normal range. I've been off test a few months and now take a small daily dose of Wellbutrin. I'm sure my t has gone down quite a bit. Do any of you guys on here take both Test and an anti depressant? If so, how are your results?
 
I was taking Lexapro, Cipralex here in Canada, prior to starting test-enth. Frankly, my "depression" was not as severe as many experience. But, I realized no improvement with the SSRI. TRT lifted the depression completely. I was also woefully low I terms of estradiol. As the article notes: "Testosterone needs estrogen's help." I believe I am proof of that.
 
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Coast - good to hear test help eliminate your depression. I'd love to get back on test because I saw some real benefits, but the anxiety and depression was worse than I had ever experienced.

Jasen - you mentioned guys who may be prone to anxiety or depression can get worse while on testosterone. why do you think that is? I love to get around that because I see some great benefit with trt. Thanks
 
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