Estradiol and Social Anxiety

[manliness1]

Ya unfortunately there is much less vitamins and minerals in our food, it’s definitely sad. You can still get pretty much everything u need from eating organs, egg yolks, fruit, red meat, grassfed raw dairy, and fatty fish, as well as getting sunlight throughout the day. The only things u’ll really need to supplement with are magnesium, a quality sea salt and vitamin D when not enough sunlight is available

If u don’t want to eat any of these foods, and want to get most of ur vitamins and minerals through supplementing, just replace ur multivitamin with a desiccated grassfed beef liver supplement. It’s nature’s multivitamin and should give u all the benefits that ur multi is giving u, without causing u any anxiety due to ratios of certain minerals being out of whack

Absolutely agreed and it is this deficiency of vitamins and minerals in our foods leading to an increase of chronic illnesses.

I also agree that that the ratios of vitamins and minerals need to be carefully balanced. Now that I think about it, before when I didn't use any supplements I had no anxiety whether it be social anxiety or otherwise. Sure, I had very low libido but I felt calm. I've noticed that my "flight or fight" mode seems to be overactive. Before when I went into a crowded place, I felt calm and no racing heart but now my heart starts racing for no reason. I have this very mild social anxiety that I'd rate 2/10 that has remained. Must be imbalanced vitamin/mineral ratios I guess.

Many thanks for your advice.

 

[newuser]

How did you resolve your dopamine receptor issue ?

Daily 30 mins meditation resets dopamine receptors and whole nervous system as well.

 

[DS3]

@Billy7 and @manliness1

Have you tried pregnenolone or progesterone supplementation?
How is your caffeine intake?
Are you worrying about something when you have anxiety?
How do you sleep?

Estradiol is not a stimulating hormone. I do not see any of you mentioning your testosterone and sensitive estradiol test results either.

In this video, Dr. Snipes discusses the complex interplay between neurotransmitters and sex hormones. She notes that estrogen can be a stimulating hormone in the CNS.

This may not be the issue with social anxiety discussed in this thread, but it’s interesting and worth noting.

 

[newuser]

Do you think it is dangerous to prescribe drugs that regulate dopamine receptors to an elderly person?

You could try Selegiline in low doses.

 

[newuser]

Do you think it is dangerous to prescribe drugs that regulate dopamine receptors to an elderly person? My father is 70 years old, he has problems with the perception of the world around him and social anxiety, and his daily course of medication exceeds all possible norms. I don't want to force him to take even more pills, even if they are regular vitamins. I have already arranged home care assistance for him so that he receives proper care even when I can't provide it to him. But I would like to make his life as easy as possible. Is it possible to do without additional pills in this case?

Any medication will only mask the symptoms. Your father needs Cognitive Behavioral Therapy. In simple words rewire brain again.

 

[Nocalves]

Hi,

I hope all is well.

I know that testosterone plays a significant role in the production and regulation of neurotransmitters such as dopamine, serotonin, GABA etcetera. If testosterone levels are low for an individuals physiological state then this can ofcourse cause social anxiety symptoms.

My question is in can low or high E2 cause social anxiety symptoms independent of testosterone levels?

From other forums (will not mention) it seems low E2 can cause social anxiety for some individuals. As estrogen is linked with serotonin production it makes sense that deficient levels could cause social anxiety and unwanted nervousness.

I would be grateful to hear everyone elses experiences in regards to E2 and social anxiety. It will be quite interesting to get more knowledge of this. Please kindly use the following format shown below.

Cause: Low E2 or High E2 (Either one or both if applicable).
Symptoms: Difficulty making eye contact, anxiety in crowded places etcetera. (This is just an example of social anxiety symptoms, please do share your specific ones if applicable).

Thank you.

Low e2 definitely cause social anxiety for me.

 

[DS3]

Do you think it is dangerous to prescribe drugs that regulate dopamine receptors to an elderly person? My father is 70 years old, he has problems with the perception of the world around him and social anxiety, and his daily course of medication exceeds all possible norms. I don't want to force him to take even more pills, even if they are regular vitamins. I have already arranged home care assistance for him so that he receives proper care even when I can't provide it to him. But I would like to make his life as easy as possible. Is it possible to do without additional pills in this case?

Has he had a cognitive examination by a neurologist or neuropsychologist? He may be displaying signs of early dementia. Also, polypharmacy, as you’ve mentioned he is taking copious amounts of supplements/pharmaceuticals, is contributor to mental decline in the elderly. Statins, mood stabilizers/antipsychotics, along with a host of other pharmaceuticals can produce dementia-like symptoms in elder people.

 

[drpub2112]

The only way to know for sure is to see how you feel at different E2 levels. Everyones individual genetics will dictate how they feel. There's just too much going on to predict how E2 modulation will effect you.

For example, I have a low producing variant of the MAO-A gene which regulates the rate that many neurotransmitters and hormones are broken down, serotonin and dopamine among the most important. MAO-A is a major correlate with lots of mental heath traits.

Estrogen levels have an inverse relationship to MAO-A levels, so high E2 from TRT drops my MAO levels even lower than normal and exacerbates all my problems with negative emotions. Whenever I get triggered and get feelings of anxiety, anger, or fear, I can't easily come back to baseline because of natually low levels of MAO-A, E2 spikes make it worse.

But if someone else has normal or high producing MAO-A gene variants, the effects of higher-than-average E2 may not be noticable at all. It might even make them feel better. Hormones, neurotransmitters, and genes are so intimately interwoven that there is no way to tell how manipulating only 1 or 2 will effect your individual mental state. In my case, the natural lowering of T with the rise of E that comes with aging makes all of the existing mental health issues I had in my youth progressively worse.

So, the only blanket statement that can really be made about it is that both low and high E2 levels can produce negative symptoms, to widly varying degrees among men. High anxiety states can definately be exacerbated by out-of-range estrogen levels.

 

[DS3]

The only way to know for sure is to see how you feel at different E2 levels. Everyones individual genetics will dictate how they feel. There's just too much going on to predict how E2 modulation will effect you.

For example, I have a low producing variant of the MAO-A gene which regulates the rate that many neurotransmitters and hormones are broken down, serotonin and dopamine among the most important. MAO-A is a major correlate with lots of mental heath traits.

Estrogen levels have an inverse relationship to MAO-A levels, so high E2 from TRT drops my MAO levels even lower than normal and exacerbates all my problems with negative emotions. Whenever I get triggered and get feelings of anxiety, anger, or fear, I can't easily come back to baseline because of natually low levels of MAO-A, E2 spikes make it worse.

But if someone else has normal or high producing MAO-A gene variants, the effects of higher-than-average E2 may not be noticable at all. It might even make them feel better. Hormones, neurotransmitters, and genes are so intimately interwoven that there is no way to tell how manipulating only 1 or 2 will effect your individual mental state. In my case, the natural lowering of T with the rise of E that comes with aging makes all of the existing mental health issues I had in my youth progressively worse.

So, the only blanket statement that can really be made about it is that both low and high E2 levels can produce negative symptoms, to widly varying degrees among men. High anxiety states can definately be exacerbated by out-of-range estrogen levels.

What an excellent post. Thank you for sharing this.

 

[Gman86]

The only way to know for sure is to see how you feel at different E2 levels. Everyones individual genetics will dictate how they feel. There's just too much going on to predict how E2 modulation will effect you.

For example, I have a low producing variant of the MAO-A gene which regulates the rate that many neurotransmitters and hormones are broken down, serotonin and dopamine among the most important. MAO-A is a major correlate with lots of mental heath traits.

Estrogen levels have an inverse relationship to MAO-A levels, so high E2 from TRT drops my MAO levels even lower than normal and exacerbates all my problems with negative emotions. Whenever I get triggered and get feelings of anxiety, anger, or fear, I can't easily come back to baseline because of natually low levels of MAO-A, E2 spikes make it worse.

But if someone else has normal or high producing MAO-A gene variants, the effects of higher-than-average E2 may not be noticable at all. It might even make them feel better. Hormones, neurotransmitters, and genes are so intimately interwoven that there is no way to tell how manipulating only 1 or 2 will effect your individual mental state. In my case, the natural lowering of T with the rise of E that comes with aging makes all of the existing mental health issues I had in my youth progressively worse.

So, the only blanket statement that can really be made about it is that both low and high E2 levels can produce negative symptoms, to widly varying degrees among men. High anxiety states can definately be exacerbated by out-of-range estrogen levels.

Would having lower MAO-A possibly be a good thing? Would that allow for neurotransmitters to be broken down at a lower rate?

I’m using selegeline, which is an MAO-B inhibitor. So it decreases the breakdown of certain neurotransmitters, mainly dopamine. MAO-A is more responsible for the breakdown of serotonin, as far as I know. But having naturally lower MAO-A or MAO-B doesn’t necessarily sound like a bad thing. Unless some of the neurotransmitters are ones that don’t make u feel that great. Like maybe adrenaline or something similar

 

[drpub2112]

Would having lower MAO-A possibly be a good thing? Would that allow for neurotransmitters to be broken down at a lower rate?

If having more norepinephrine and serotonin in your brain reduces your anxiety and allows you to think more camly and clearly then yes, of course. But, if having more neurotransmitters induces anxiety, anger, fear, and cognitive dissonance, then no, it's bad.

It all comes down to your personal genetics. Some people do great on MOA inhibiting substances. There are alot of different genes that make up your personality traits and overall resilience to stress. They interact in complex ways but MAO-A is the major determinant of CSF serotonin and norepinephrine levels. Androgens lower MAO-A specifically by the conversion of T to E. In the following study, T also increased MAO-B.

ANDROGEN METABOLITES IMPACT CSF AMINES AND AXONAL SEROTONIN VIA MAO-A AND -B IN MALE MACAQUES - PMC

A number of studies have shown that mutations or deletions of the monoamine oxidase-A (MAO-A) gene cause elevated CNS serotonin and elevated impulsive aggression in humans and animal models. In addition, low cerebrospinal fluid (CSF) 5-hydroxyindole ...

www.ncbi.nlm.nih.gov

The internet frequently promotes the notion that emotional disturbances are primarily caused by low neurotransmitter levels. So the obvious thing to deduce is that more serotonin is better. For many people (maybe a majority? idk) this works out OK, because they are either MAO-A normals or high producers. But if you are a low MAO-A producer, things that further supress MAO-A will make you feel much worse, very quickly.

The only point I'm trying to make with my post is that MAO-A genes (among others) are probably what dictates a persons tolerance for elevated E2 on TRT or a high E2:T ratio before TRT. People with naturally high OR low MAO-A production likely have a history of mental health issues because of it's direct effect on neurotransmission. E2 makes me batshit crazy, but I've seen guys on youtube with E2 of 60pg/DL saying they feel fine. Everyone is different.

 

[DS3]

High-dose testosterone treatment reduces monoamine oxidase A levels in the human brain: A preliminary report

The sex hormones testosterone and estradiol influence brain structure and function and are implicated in the pathogenesis, prevalence and disease cour…

www.sciencedirect.com

 

[drpub2112]

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.

Recent research employing gender-affirming hormone treatment (GHT) of gender dysphoric individuals and utilizing positron emission tomography (PET) indicates increased serotonin transporter binding upon high-dosages of testosterone treatment. Here, we investigated the effects of GHT on levels of monoamine oxidase A (MAO-A), another key target of antidepressant treatment.

What??? They are literally saying that high dose testosterone works in exactly the opposite way of Prozac! SSRIs inhibit serotonin transporter binding. They're saying that they're following up on previous studies showing that high dose testosterone works to lower 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 E increases serotonin via MAOA inhibition and T lowers serotonin 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 both 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.

 

[Nelson Vergel]

Interesting nasal spray

https://www.vistagen.com/news-releases/news-release-details/vistagen-announces-positive-top-line-results-phase-3-palisade-2/

 

[TLR]

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 exactly the opposite way of Prozac! SSRIs inhibit serotonin transporter binding. They're saying that they're following up on previous studies showing that high dose testosterone works to lower 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 E increases serotonin via MAOA inhibition and T lowers serotonin 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 both 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.

I am highly interested in this, so I’m bumping it to see if there is any more info. Dr. Kominiarek made a video about persons with certain MAO-A SNPs not being able to tolerate androgens / estrogens. My degree is in the social science side of things, and I cheated and kicked my way through math and biology, so I barely understand enough to ask an intelligent question

On a personal level, I wonder if this is why Zoloft seemed to stop working for me for anxiety / panic after I started on TRT, and I developed a social anxiety that was never there before. I am at the point where Clonazepam is the only thing that works, but I’m really not wanting to stay on it for life (but I will before I go back to how I was before).

My question is, if I go get tested for MAO-A / COMT/ etc., how is that information going to help me determine what ( if any) action to take. I’ve already tried a restart protocol and I’m too old and been shut down too long, so my balls are a thing of the past. I think I’m just one of those guys that was never meant to be on the higher end of the range and have suspected that for a while now. All of you science / chemistry folks and researchers feel free to jump in!

 

[Jim Marlowe]

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 exactly the opposite way of Prozac! SSRIs inhibit serotonin transporter binding. They're saying that they're following up on previous studies showing that high dose testosterone works to lower 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 E increases serotonin via MAOA inhibition and T lowers serotonin 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 both 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.

drpub2112 This is a great post. I think you are spot on. Increased serotonin is central to many health problems. But with a slow MAO-A gene, exogenous T effectively results in an imbalance of serotonin to dopamine. Both go up on T administration, but serotonin remains high in those with the slow MAO-A gene because the enzyme does not clear it as fast. Obviously that is a gross oversimplification of a complex process involving 5-HT, but essentially that is what happens. The only quibble I would have is men only have one copy of the gene at RS6323 (R297R) because it is inherited on the X chromosome. So if you are male, then you are just +, not +/+. That would be the T allele if you are slow MAO-A. G is the "fast" version. And the literature suggests women have different expression from the alleles than men. I suspect there will be much more insight into these issues with the advent of affordable whole-genome sequencing.​