Progesterone dominance and emotional lability? Or something else?

PeskyPeater

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Pregnenolone is preferentially converted to ALLO, a deficiency of PREG can have the effect of emotional instability.

Allopregnanolone Elevations Following Pregnenolone Administration Are Associated with Enhanced Activation of Emotion Regulation Neurocircuits


Conclusions

These results demonstrate that in response to emotional stimuli, allopregnanolone reduces activity in regions associated with generation of negative emotion. Furthermore, allopregnanolone may enhance activity in regions linked to regulatory processes. Aberrant activity in these regions has been linked to anxiety psychopathology. These results thus provide initial neuroimaging evidence that allopregnanolone may be a target for pharmacologic intervention in the treatment of anxiety disorders and suggest potential future directions for research into neurosteroid effects on emotion regulation neurocircuitry.
 

PeskyPeater

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Sigma1 (sigma 1) receptor agonists and neurosteroids attenuate B25-35-amyloid peptide-induced amnesia in mice through a common mechanism - PubMed

Abstract

The sigma1 (sigma 1) receptor agonists exert potent anti-amnesic effects, as they apparently block the learning impairments either induced by the muscarinic receptor antagonist scopolamine, the N-methyl-D-aspartate receptor antagonist dizocilpine or inherently due to the age-related deficits in senescence-accelerated mice. We recently described the amnesia induced by the beta-amyloid-related peptide beta 25-35, administered centrally in an aggregated form, in mice. The deficits were sensitive to cholinomimetics or to N-methyl-D-aspartate/glycine modulatory site agonists. Herein, we examined the effects of sigma 1 receptor ligands on the beta 25-35 peptide-induced amnesia. The effects of neuro(active) steroids, which interact in vitro and in vivo with sigma 1 receptors were examined in parallel. Mnesic capacity was evaluated seven days after administration of aggregated beta 25-35 peptide (3 nmol), using spontaneous alternation in the Y-maze for spatial short-term memory, or after 14 days, using the step-down type passive avoidance test for long-term memory. The sigma 1 receptor agonists (+)-pentazocine, PRE-084, or SA4503 attenuated, in a dose-dependent and bell-shaped manner, the beta 25-35 peptide-induced deficits on both tests. These effects were antagonized by haloperidol or BMY-14802, confirming the sigma 1 receptor pharmacology. Pregnenolone, dehydroepiandrosterone, and their sulphate esters, but not progesterone, also dose-dependently attenuated the beta 25-35 peptide-induced deficits. Progesterone blocked the beneficial effects of each other neurosteroid, behaving as an antagonist. Furthermore, haloperidol blocked the effects induced by neurosteroids, whereas progesterone antagonized the effects of the non-steroidal sigma 1 receptor agonists, showing a clear crossed pharmacology of different drug classes. These results demonstrate that: (i) the anti-amnesic effect of sigma 1 receptor agonists may be of therapeutic relevance in pathological states affecting the cholinergic and/or glutamatergic systems, such as in pathological aging; (ii) neurosteroids play an important role in learning processes and may collectively constitute a therapeutic target; (iii) the interaction between sigma 1 systems and neurosteroids appears indeed of behavioural relevance.
 

PeskyPeater

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Normally I'd say absolutely 100%. But in my case, I have a medication induced brain injury and now tapering off another highly toxic drug. It's a mess. I do take thyroid and my tests are pretty good now. I'd ovulated but my brain isn't able to deal with the roller coaster at this point. It's a crap road, and I hate my doctor. But it's my fault for taking the drug and trusting too. But none of that matters at this point. I just have to find a way to heal.
no it's not your fault, you shouldn't take it on yourself.
When I was in rehab for cannabis and alcohol addiction, I suggested to the shrink it would be a good idea to use a SSRI for my anxiety and he agreed it was good option. I did not know any better then. And the professional wasn't wrong either, just using the information at hand he has been taught. I was not aware of the propaganda of the industry that is controlling information. Bummer. Better luck next time. Now we know better, have your own effort to thank that you now have found a higher perspective of things and can be proud of that. And so you can trust yourself and your body's ability to heal.
 
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no it's not your fault, you shouldn't take it on yourself.
When I was in rehab for cannabis and alcohol addiction, I suggested to the shrink it would be a good idea to use a SSRI for my anxiety and he agreed it was good option. I did not know any better then. And the professional wasn't wrong either, just using the information at hand he has been taught. I was not aware of the propaganda of the industry that is controlling information. Bummer. Better luck next time. Now we know better, have your own effort to thank that you now have found a higher perspective of things and can be proud of that. And so you can trust yourself and your body's ability to heal.
That's kind of you to say. You are right - it isn't our faults and even our doctor's are trying their best. I sure hope I can heal. There are enough terrifying stories on the internet that I am not going to rely to time alone (which is why I am looking into anything that might help to heal the brain).
 

Frankdee20

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Everyone likes to take things based on very little information they receive and this leads to unforseen problems. Progesterone is not a pro-gaba substance. No hormone can be classified as this one dimensional. Progesterone can increase sex hormones by inhibiting GABA in the medial preoptic area which is an important area needed for sex hormone production. So in this way, it can be good. But the other issue is it also decreases GABA in the amygdala by decreasing GAD enzyme (which makes GABA from glutamate). This leads to higher glutamatergic activity in the amygdala which is an area in the brain involved in emotion. You can easily imagine how by exciting the amygdala this can cause emotional lability.

What exactly are you trying to heal in your brain?
This forum is full of one dimensional biases.
 
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@PeskyPeater Is this receptor also involved in the production of sex hormones?
 

June

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That's kind of you to say. You are right - it isn't our faults and even our doctor's are trying their best. I sure hope I can heal. There are enough terrifying stories on the internet that I am not going to rely to time alone (which is why I am looking into anything that might help to heal the brain).
Is there an update? I made the mistake of taking benzo’s in 2014 and it’s still taking it’s toll on my system. Was the progesterone the solution?
 

June

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@themartian1000
I am currently aiming to heal my brain using high dose progesterone (I read an interesting account on this forum Progesterone for recovering addict).

However, I have recently had some issues that I've never felt before (tearful, emotional, irritable) since starting progesterone. I've been using Health Natura progesterone that I put into capsules and take with a fatty snack and orange juice. I have aimed for 60mg doses around every 4-6 hours. This is in addition to the suppositories and prometrium I am taking, though I am hoping to phase those out. I have 800mg suppositories, 500mg prometrium and about 300mg Health Natura. However, I know a lot may not be absorbed.

I have done a lot of testing, and my estrogen is normal on the lower end, progesterone at the high end (this was when I was using prometrium and suppositories), so I think things are ok. Thyroid is stable on cytomel (cannot tolerate T4 and never could - on for several years). Diet is pretty Peaty with a lot of milk, orange juice, carbs, low PUFA, etc. Vitamin D is 60, and other labs appear fine.

So, my question is, can I be progesterone dominant now, which is causing all of this? My understanding from reading Ray Peat's stuff is that progesterone is quite safe even at high doses and should not cause problems. I don't think it is estrogen based on labs, so I am not sure what is going on. Is allopregnanolone fluctuating a lot, creating mini-withdrawal? Too much GABAergic (but I thought this would be calming), too little estrogen (seems unlikely).

I'm so confused and really want to heal my poor brain. My doctor took me off a prescribed benzo that I was on just 3 months, but the low progesterone at that time likely left my brain bare. I had a 10 month horror show, put on a medicine called pregabalin (now tapering that but has been stable), and just want my brain and life back!!! I will never take another pharmaceutical again as long as I live!!!
Just a little update. I followed your protocol of upping to 1600mg progesterone for my heavy bleeding and brain injury, using different mediums and my word! After I switched the Prometrium to sublingual, i became so sedated!! I stumbled as I walked as every object started moving. This is either what drunk feels like or being high. My legs feel like jelly. Not sure if I should sleep it off each time or I should just lower to 1300-1400mg. I don’t know how you didn’t get these effects! Curious if you still take the same dose. Would surprise me if you are taking an even higher dose.
 
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However, I have recently had some issues that I've never felt before (tearful, emotional, irritable) since starting progesterone.
I have experienced the same with Progest-E and quit using it because of that. It was making me emotional. I figured since it is the hormone of youth and children are big cry babies and throw temper tantrums I didn’t need it anymore. So you may be right you are progesterone dominant. Though Ray Oeat said it is safe at any dose, he doesn’t recommend using it just because either. In old age a minimal dose may be useful daily or in sickness. I strongly suggest, since you are using the progesterone for a different purpose than I did, to support your process with plenty of protein in the morning and during the day and sedate yourself with carbs and fats at night. Those grains trigger the opiate part of the brain and aren’t optimal for anything, especially healing. Sprouted has been a wonderful switch for me to get my grain fix. Sprouted doesn’t carry minerals out of the body, like regular grains do, which depletes the teeth, bones and THE BRAIN. Here is my thread linked below with everything I have found useful and interesting about it posted there…


 

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