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<blockquote data-quote="drpub2112" data-source="post: 229819" data-attributes="member: 42634"><p>Hi DS3. I read that study too. I think the headline is misleading though. My thoughts are this.</p><p></p><p>That study was done on FTM (biological females) in transition. Obviously, the effect of high dose testosterone on female brains could be very different than biological males. I also read somewhere else that confirmed the gigantic drop in estrogen right after childbirth causes a huge increase in MAO in female brains. Since that moves MAO in the opposite direction of an MAOI antidepressant drug, they speculated that this is likely the cause behind postpartum depression. If that is true it would really bolster the low serotonin theory of depression. At least, in postpartum in women.</p><p></p><p>The problem with the serotonin theory of course, is that increasing serotonin makes some people's anxiety and depression way worse, along with making them tired and impotent. I can't imagine an MAOI drug providing any kind of relief to a middle aged hypogonadal man. :/ Certainly not me.</p><p></p><p>But this is actually the line in your study that gets my full attention. It was in the introduction.</p><p></p><p></p><p></p><p>What??? They are literally saying that high dose testosterone works in <u>exactly the opposite</u> way of Prozac! SSRIs <u>inhibit</u> serotonin transporter binding. They're saying that they're following up on previous studies showing that high dose testosterone works to <u>lower</u> serotonin levels at the level of SERT. Wow. I did not know that.</p><p></p><p>Anyhow, the study I referenced about E and MAO was actually done on male monkeys. And in it they specifically found that E lowered MAO expression while T itself had no direct effect. They determined that the conversion of T to E is what actually lowered the MAO levels.</p><p></p><p>If that's true, then it seems that <u>E increases serotonin</u> via MAOA inhibition and <u>T lowers serotonin</u> via promotion of SERT. So, everyone on TRT is actually trying to lower serotonin and increase dopamine until they find just the right balance for them. My theory is that when we don't manage E well, we end up with <u>both</u> higher dopamine and serotonin. People with high functioning MAO-A/B and COMT genes can handle it well. But those of us who have genetic difficulty with braking down monoamines struggle with harsh symptoms until we get our levels dialed in.</p><p></p><p>I think that female depression is likely more serotonergic in nature, while male depression is much more dopaminergic. Just like T and E are gender-aligned. The main reason being the differences in the sheer number of androgen and estrogen receptors in our brains. Like anything else though, it would surely be on a spectrum because of such a huge variation in other important genetic traits.</p><p></p><p>Thanks for the post. I thought I was the only one who cared about how hormones effect MOA genes. <img src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" class="smilie smilie--sprite smilie--sprite1" alt=":)" title="Smile :)" loading="lazy" data-shortname=":)" /></p><p></p><p>BTW... I actually really only care about this stuff because I know I'm +/+ MAO-A R297R. It's among the most strongly effected genetic variants for low producing MAO-A. I have a lot of mental health issues that both worsen and improve with hormone treatment. Nothing other than hormones have helped me at all so, the topic is especially interesting to me. That's the only reason I'm here sounding like a know-it-all. Honestly, I don't sit around all day thinking about this stuff <img src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" class="smilie smilie--sprite smilie--sprite1" alt=":)" title="Smile :)" loading="lazy" data-shortname=":)" /></p><p></p><p>Fuck. I wrote a novel. Sorry.</p></blockquote><p></p>
[QUOTE="drpub2112, post: 229819, member: 42634"] Hi DS3. I read that study too. I think the headline is misleading though. My thoughts are this. That study was done on FTM (biological females) in transition. Obviously, the effect of high dose testosterone on female brains could be very different than biological males. I also read somewhere else that confirmed the gigantic drop in estrogen right after childbirth causes a huge increase in MAO in female brains. Since that moves MAO in the opposite direction of an MAOI antidepressant drug, they speculated that this is likely the cause behind postpartum depression. If that is true it would really bolster the low serotonin theory of depression. At least, in postpartum in women. The problem with the serotonin theory of course, is that increasing serotonin makes some people's anxiety and depression way worse, along with making them tired and impotent. I can't imagine an MAOI drug providing any kind of relief to a middle aged hypogonadal man. :/ Certainly not me. But this is actually the line in your study that gets my full attention. It was in the introduction. What??? They are literally saying that high dose testosterone works in [U]exactly the opposite[/U] way of Prozac! SSRIs [U]inhibit[/U] serotonin transporter binding. They're saying that they're following up on previous studies showing that high dose testosterone works to [U]lower[/U] serotonin levels at the level of SERT. Wow. I did not know that. Anyhow, the study I referenced about E and MAO was actually done on male monkeys. And in it they specifically found that E lowered MAO expression while T itself had no direct effect. They determined that the conversion of T to E is what actually lowered the MAO levels. If that's true, then it seems that [U]E increases serotonin[/U] via MAOA inhibition and [U]T lowers serotonin[/U] via promotion of SERT. So, everyone on TRT is actually trying to lower serotonin and increase dopamine until they find just the right balance for them. My theory is that when we don't manage E well, we end up with [U]both[/U] higher dopamine and serotonin. People with high functioning MAO-A/B and COMT genes can handle it well. But those of us who have genetic difficulty with braking down monoamines struggle with harsh symptoms until we get our levels dialed in. I think that female depression is likely more serotonergic in nature, while male depression is much more dopaminergic. Just like T and E are gender-aligned. The main reason being the differences in the sheer number of androgen and estrogen receptors in our brains. Like anything else though, it would surely be on a spectrum because of such a huge variation in other important genetic traits. Thanks for the post. I thought I was the only one who cared about how hormones effect MOA genes. :) BTW... I actually really only care about this stuff because I know I'm +/+ MAO-A R297R. It's among the most strongly effected genetic variants for low producing MAO-A. I have a lot of mental health issues that both worsen and improve with hormone treatment. Nothing other than hormones have helped me at all so, the topic is especially interesting to me. That's the only reason I'm here sounding like a know-it-all. Honestly, I don't sit around all day thinking about this stuff :) Fuck. I wrote a novel. Sorry. [/QUOTE]
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