High Progesterone / Pregnenolone - RU486

[tjanok]

Two years since developing PFS, and immediately after the cash. My blood serum preg/prog have been elevated. Elevated cortisol as well.
Even after two years, they have not fallen, but are on the decline.

(Additionally, all liver/thyroid checked, hair analysis, gut biome. Nothing to report)

Currently on a carnivore diet, TRT (for low free t, and elevated SHGB. Androgens looks great now), a slew of supplements that help sleep and mood.
But I suffer greater with cognitive dysfunction, general "brain fog" that's been 24/7 since ceasing fin. Taking prog increases the fog, oral or trans dermal.

Reading a few antidotes here, and coming across this:

Resetting the Stress System with a Mifepristone Challenge - Cellular and Molecular Neurobiology

Psychotic depression is characterized by elevated circulating cortisol, and high daily doses of the glucocorticoid/progesterone antagonist mifepristone for 1 week are required for significant improvement. Using a rodent model, we find that such high doses of mifepristone are needed because the...

link.springer.com

I went ahead and had 5g of RU486 produced. Unsure how I'll administer it, or properly dissolve it for oral consumption. But this will be my next attempt at improving my brain function.
Ella is mentioned here, which I assume acts in a similar manner. Anyone else take RU486 directly? And would anyone have any recommendations on a recommend dissolving agent/administration of the pure powder?

 

[bruschi11]

RU the same one that gbold proposed way back when right? I think it is.

Yea it helped me get some sexual function back. But honestly trt, all out hormone approach and that’s what you’re looking at.

I’d just stop. Get off everything. Let body balance out. Run plasma aminos in blood, look at minerals and fix from the ground up.

It might sound crazy but the best thing about pfs for me back then was once I realized health wasn’t about hormones I found my way forward. Yes you want the hormones to be regulated. I had psycho high preg early in pfs and low T.

The hormone era was the 2000s to mid 2010s IMO. The 2020s are about optimizing your system so the body creates it’s own hormones in balance.

Zinc finger approach is about regulating cortisol. Keeps it from soaring.

Is your cholesterol low? It could be getting drained to preg for some reason.

Lastly… yea RU can create big changes. I’d just hold onto it. Stop everything including testosterone. Literally stop everything. Once you start moving forward then you give RU say a 3 day cycle.

 

[zancek0]

Have you had DHT and E2 tested too?

Maybe it's best to first try to figure out which system is affected so that brain fog seems to be so persistent.
What other symptoms do you have?
How do you respond to alcohol in terms of brain fog?

 

[tjanok]

Have you had DHT and E2 tested too?

Maybe it's best to first try to figure out which system is affected so that brain fog seems to be so persistent.
What other symptoms do you have?
How do you respond to alcohol in terms of brain fog?

RU the same one that gbold proposed way back when right? I think it is.

Yea it helped me get some sexual function back. But honestly trt, all out hormone approach and that’s what you’re looking at.

I’d just stop. Get off everything. Let body balance out. Run plasma aminos in blood, look at minerals and fix from the ground up.

It might sound crazy but the best thing about pfs for me back then was once I realized health wasn’t about hormones I found my way forward. Yes you want the hormones to be regulated. I had psycho high preg early in pfs and low T.

The hormone era was the 2000s to mid 2010s IMO. The 2020s are about optimizing your system so the body creates it’s own hormones in balance.

Zinc finger approach is about regulating cortisol. Keeps it from soaring.

Is your cholesterol low? It could be getting drained to preg for some reason.

Lastly… yea RU can create big changes. I’d just hold onto it. Stop everything including testosterone. Literally stop everything. Once you start moving forward then you give RU say a 3 day cycle.

No other symptoms.
All my other issues after stopping fin, insomnia, unbelievable depression, fatigue, random aches/pains, minor sexual dysfunction, and watery semen has stopped. Took about a year and a half.
Alcohol makes it significantly worse. Entering the "buzzed" state is more like entering a total disassocation MDMA trip at this point.
--

Yeah, gbold. How long did it take you to make it somewhat out of the "PFS-state"?

I would like to come off of TRT, and I tried once, but my androgen's almost immediately flip back to their crap state. (Over range SHGB, low E2, low free T, normal total t). And fatigue returns.
The carnivore diet, or at least low carb, helps immensely in keeping the fog from going to a suicidal state. (it's 24/7, but it can become unbearable if I'm not careful)

All thyroid RT3/RT4, TSH/FSH are back to my pre-fin state, including my body temp.
Liver values good. All your other typical values match my pre-fin state. (I did a ton of bloodwork prior to fin, thinking i was being smart)

Anyways, I am on no supplements as of now. Never tested my plasma amino, and will do that next. A gut map didn't show much, some slightly overgrowth of one or two strains, but nothing crazy. Other than my IgA values were x4 the range, so I assume inflammation response(?)

A recent hair analysis didn't show anything super remarkable as well:


Did a urine test as well, but I could never verify why urine androgens would be so high.
(This was before TRT/HCG)


But here's what I have found in the last two years, specifically for the cognitive issues. Any other insight would be hugely appreciated.
(All I can gather, based on the dopamine response, is any pathway relating to/from dopamine is where my issue is stemming from)

Adderall, and dopamine antagonists improve it. But very mildly.
Benzos do nothing. Wipe away anxiety, as they should, but does nothing for the fog. So I wrote off GABA quickly.
Processed junk, sugar, crap diet always makes it worse. High Carb = Worse, (Clean) Low Carb = Better
HCG, SERMS, every single popular peptide, common amino stack for cognitive function, never did a single thing.


Have obviously avoided SSRIs.
So, for the most part, still at a loss where the brain issue is stemming from, sadly.

 

[bruschi11]

No other symptoms.
All my other issues after stopping fin, insomnia, unbelievable depression, fatigue, random aches/pains, minor sexual dysfunction, and watery semen has stopped. Took about a year and a half.
Alcohol makes it significantly worse. Entering the "buzzed" state is more like entering a total disassocation MDMA trip at this point.
--

Yeah, gbold. How long did it take you to make it somewhat out of the "PFS-state"?

I would like to come off of TRT, and I tried once, but my androgen's almost immediately flip back to their crap state. (Over range SHGB, low E2, low free T, normal total t). And fatigue returns.
The carnivore diet, or at least low carb, helps immensely in keeping the fog from going to a suicidal state. (it's 24/7, but it can become unbearable if I'm not careful)

All thyroid RT3/RT4, TSH/FSH are back to my pre-fin state, including my body temp.
Liver values good. All your other typical values match my pre-fin state. (I did a ton of bloodwork prior to fin, thinking i was being smart)

Anyways, I am on no supplements as of now. Never tested my plasma amino, and will do that next. A gut map didn't show much, some slightly overgrowth of one or two strains, but nothing crazy. Other than my IgA values were x4 the range, so I assume inflammation response(?)

A recent hair analysis didn't show anything super remarkable as well:
View attachment 1783

Did a urine test as well, but I could never verify why urine androgens would be so high.
(This was before TRT/HCG)
View attachment 1784

But here's what I have found in the last two years, specifically for the cognitive issues. Any other insight would be hugely appreciated.
(All I can gather, based on the dopamine response, is any pathway relating to/from dopamine is where my issue is stemming from)

Adderall, and dopamine antagonists improve it. But very mildly.
Benzos do nothing. Wipe away anxiety, as they should, but does nothing for the fog. So I wrote off GABA quickly.
Processed junk, sugar, crap diet always makes it worse. High Carb = Worse, (Clean) Low Carb = Better
HCG, SERMS, every single popular peptide, common amino stack for cognitive function, never did a single thing.


Have obviously avoided SSRIs.
So, for the most part, still at a loss where the brain issue is stemming from, sadly.

The htma tells me a lot. The high copper is a problem. Next to low iron (that 8.4 is a lot lower than the chart makes it out to be trust me. I think ARL / tei would show they way lower.) Next to low na/k and both cr/ V being low.

I’m seeing glutathione recycling issues. NRF2 and coenzyme A issues. Myself and a girl I talk to have had this similar pattern recurring on htmas. And b5 as pantithene start LOW LOW dose could be big here. Pantothenic might do the job. Maybe a combo of both.

OATs/Nutreval and/or plasma amino acids would be helpful here. See if doc would just do plasma aminos for u- quick and simple.

With cr/ V down and manganese with high copper I see horrid issues getting to Arginine and ornithine. Urea cycle must be down. You must have lost your vains in your arms right?

You never took a lot of biotin for some reason did you?

This htma tells me a lot. I’ve had a similar pattern recently on two occasions and it’s very treatable. Gotta get off the trt to do so though.

 

[RebelWithACause]

Pretty sure if you are on hormones and you do a HTMA the results are skewed (/useless).

 

[tjanok]

Pretty sure if you are on hormones and you do a HTMA the results are skewed (/useless).

I wasn't aware of this, interesting...

The htma tells me a lot. The high copper is a problem. Next to low iron (that 8.4 is a lot lower than the chart makes it out to be trust me. I think ARL / tei would show they way lower.) Next to low na/k and both cr/ V being low.

I’m seeing glutathione recycling issues. NRF2 and coenzyme A issues. Myself and a girl I talk to have had this similar pattern recurring on htmas. And b5 as pantithene start LOW LOW dose could be big here. Pantothenic might do the job. Maybe a combo of both.

OATs/Nutreval and/or plasma amino acids would be helpful here. See if doc would just do plasma aminos for u- quick and simple.

With cr/ V down and manganese with high copper I see horrid issues getting to Arginine and ornithine. Urea cycle must be down. You must have lost your vains in your arms right?

You never took a lot of biotin for some reason did you?

This htma tells me a lot. I’ve had a similar pattern recently on two occasions and it’s very treatable. Gotta get off the trt to do so though.

Never took biotin.

I setup a time already to get amino profile down, so I'm curious what that reports. Interesting comment on the veins, I did notice there not as prominent as before. I really have no problem coming off TRT, it's just the fatigue that comes rushing in. But with the summer season coming to the end, I can probably get through it.

Never supplemented B5 in anyway before as well.

 

[zancek0]

I'd want to understand why hormone levels are so high in urine. Body is excreting them excessively. Doesn't need them due to receptor overexpression or too much signalling? Something else? Dont know. DHEA is high - potent GABA A antagonist and a very strong estrogen receptor beta agonist. Why isn't it converting further into other metabolites (via 3b-hsd and 17b-hsd, say)? Testosterone very high - why isn't more converting to estradiol, for example? High NADPH requirement? ...
Like it seems your body is producing a lot of stuff but it is excreting it excessively. That is part of some regulatory and compensatory mechanisms - body is trying to lose the hormones either because it doesnt need them or because it thinks retaining them would throw it out of balance (especially with regards to minerals).

I agree that TRT can mess with HTMA drastically. Low iron on hair test? Yes, since testosterone retains it, for example.

High prog/preg in blood. We can ask ourself same questions - why isn't body converting them further. Does it need them (in the sense of them having some specific needed properties by themselves) or would the conversion further mess up the overall balance (so it blocks the enzymes that convert them)? High cortisol - again, why is it high. Body is trying to decrease inflammation? Also in cases of low stomach acid it can increase to ensure aminos get into blood. Etc. Dysregulated cortisol signalling is a huge issue in PFS.

Severe reaction to alcohol is a hint. Heavily increases acetaldehyde load, which I suspect is already an issue with you due to overgrowth of acetaldehyde producing microbes. I wonder how you would react to Rifaximin. It helps with SIBO tremendously (but usually temporarily). Have you tried antibiotics or antifungals yet (I dont recommend, just wondering)? Your brain fog is very likely to due chronic infections which make your leaky gut (or whatever mucosal tissue is affected and damaged) worse. Might be worth trying supplementing with very high doses of Wobenzym N (if you're in USA) or other similar systemic enzymes.

Does any supplement, herb, whatever noticeably alleviate this brain fog (aside from what you've mentioned already)?

 

[bruschi11]

I wasn't aware of this, interesting...


Never took biotin.

I setup a time already to get amino profile down, so I'm curious what that reports. Interesting comment on the veins, I did notice there not as prominent as before. I really have no problem coming off TRT, it's just the fatigue that comes rushing in. But with the summer season coming to the end, I can probably get through it.

Never supplemented B5 in anyway before as well.

I was going to say “if you can tolerate getting off TRT.” But I’m going to say… just do it.

I went through it in ‘17. I was badly bedridden either way. But it was scary seeing my dick shrink and balls sucked up to my body. It all came back when I got better. I don’t think that’s what happens to you right? Just fatigue gets bad.

Look at this as just a chronic illness. A poor body chemistry. PFS triggered poor functioning methylation/ Krebs. Nitric Oxide system is down.

The high copper is the high Dhea. Copper converts pregnenolone to Dhea. We want that pregnenolone converting to progesterone. And you’re saying prog is high too. Well your zinc is high so you’re getting to both.

So progesterone to cortisol… THAT involves fe3 which I see as hair iron. Is there an infection stealing hair iron/ fe3? That’s possible. Or it could just be fact NRF2/ CoA is down. Overall Nitric Oxide system is down. Again I’m looking at b5.

But once b5 is in that will pressure manganese (already low). You’re probably gonna need zinc manganese with it. This will pressure biotin. And eventually magnesium. B2 b12 b1 might need to come into play. Hopefully not. That’s why I say keep b5 low.

I think gbold was so close to solving this all for everyone. I think b5 targeting CoA /NRF2 is something he missed out on in urea cycle. He mentioned zinc biotin manganese a lot for urea cycle but I don’t think anyone really gets the fact you need NRF2 , gluth recycling for Arginine from citrulline. It took extensive research on my part to solve that part.

We go nowhere no matter what without glutathione and it’s recycling. If that’s the case you’re gonna be stuck at SAH and methylation won’t function. We need both NAD and glutathione to use copper. Without these you get killed by copper. And you’re absolutely getting hit by copper.

I think you’re doing good with NAD right now. That could change. I see the sulfur in hair that tells me you are getting down CDO and you are probably making histidine from NaD. Is FAD (b2) ok? Maybe not. That could be part of this.

B6 needs to stay active as well. Which needs b2. B5 might need b2 here to help you. A lot of times iron drops in hair in just flat out b2 deficiency.

Another thing I’m liking for testing right now is biofeedback machine. You can try to find a provider in your area likely if you’re in the states. I’m strongly considering buying one myself and becoming a practitioner. You can get a really good view of b vitamin status.

Gbold tried with us and some people got better but some people needed more advanced and frequent testing. He said it himself “ I tested like crazy.”

 

[tjanok]

I'd want to understand why hormone levels are so high in urine. Body is excreting them excessively. Doesn't need them due to receptor overexpression or too much signalling? Something else? Dont know. DHEA is high - potent GABA A antagonist and a very strong estrogen receptor beta agonist. Why isn't it converting further into other metabolites (via 3b-hsd and 17b-hsd, say)? Testosterone very high - why isn't more converting to estradiol, for example? High NADPH requirement? ...
Like it seems your body is producing a lot of stuff but it is excreting it excessively. That is part of some regulatory and compensatory mechanisms - body is trying to lose the hormones either because it doesnt need them or because it thinks retaining them would throw it out of balance (especially with regards to minerals).

I agree that TRT can mess with HTMA drastically. Low iron on hair test? Yes, since testosterone retains it, for example.

High prog/preg in blood. We can ask ourself same questions - why isn't body converting them further. Does it need them (in the sense of them having some specific needed properties by themselves) or would the conversion further mess up the overall balance (so it blocks the enzymes that convert them)? High cortisol - again, why is it high. Body is trying to decrease inflammation? Also in cases of low stomach acid it can increase to ensure aminos get into blood. Etc. Dysregulated cortisol signalling is a huge issue in PFS.

Severe reaction to alcohol is a hint. Heavily increases acetaldehyde load, which I suspect is already an issue with you due to overgrowth of acetaldehyde producing microbes. I wonder how you would react to Rifaximin. It helps with SIBO tremendously (but usually temporarily). Have you tried antibiotics or antifungals yet (I dont recommend, just wondering)? Your brain fog is very likely to due chronic infections which make your leaky gut (or whatever mucosal tissue is affected and damaged) worse. Might be worth trying supplementing with very high doses of Wobenzym N (if you're in USA) or other similar systemic enzymes.

Does any supplement, herb, whatever noticeably alleviate this brain fog (aside from what you've mentioned already)?

No supplement or herb has ever curbed the fog, even a little. Only anti fungal/antibiotic I've tried, if it counts, is Nystatin (orally/tablet). In large doses. Nothing to report from that.
I have a slew of antibiotics at my disposal, as I was going to go down the SIBO/gut route eventually. But other than diet, haven't really tried much for it. Thanks for insight, extremely helpful. I like to try and keep a buffer of possibilities/things to attempt at my disposable.

I was going to say “if you can tolerate getting off TRT.” But I’m going to say… just do it.

I went through it in ‘17. I was badly bedridden either way. But it was scary seeing my dick shrink and balls sucked up to my body. It all came back when I got better. I don’t think that’s what happens to you right? Just fatigue gets bad.

Look at this as just a chronic illness. A poor body chemistry. PFS triggered poor functioning methylation/ Krebs. Nitric Oxide system is down.

The high copper is the high Dhea. Copper converts pregnenolone to Dhea. We want that pregnenolone converting to progesterone. And you’re saying prog is high too. Well your zinc is high so you’re getting to both.

So progesterone to cortisol… THAT involves fe3 which I see as hair iron. Is there an infection stealing hair iron/ fe3? That’s possible. Or it could just be fact NRF2/ CoA is down. Overall Nitric Oxide system is down. Again I’m looking at b5.

But once b5 is in that will pressure manganese (already low). You’re probably gonna need zinc manganese with it. This will pressure biotin. And eventually magnesium. B2 b12 b1 might need to come into play. Hopefully not. That’s why I say keep b5 low.

I think gbold was so close to solving this all for everyone. I think b5 targeting CoA /NRF2 is something he missed out on in urea cycle. He mentioned zinc biotin manganese a lot for urea cycle but I don’t think anyone really gets the fact you need NRF2 , gluth recycling for Arginine from citrulline. It took extensive research on my part to solve that part.

We go nowhere no matter what without glutathione and it’s recycling. If that’s the case you’re gonna be stuck at SAH and methylation won’t function. We need both NAD and glutathione to use copper. Without these you get killed by copper. And you’re absolutely getting hit by copper.

I think you’re doing good with NAD right now. That could change. I see the sulfur in hair that tells me you are getting down CDO and you are probably making histidine from NaD. Is FAD (b2) ok? Maybe not. That could be part of this.

B6 needs to stay active as well. Which needs b2. B5 might need b2 here to help you. A lot of times iron drops in hair in just flat out b2 deficiency.

Another thing I’m liking for testing right now is biofeedback machine. You can try to find a provider in your area likely if you’re in the states. I’m strongly considering buying one myself and becoming a practitioner. You can get a really good view of b vitamin status.

Gbold tried with us and some people got better but some people needed more advanced and frequent testing. He said it himself “ I tested like crazy.”

That's correct, sexual function/physical attributes don't seem to be affected by TRT on or off. Just mood/energy plummets.
Once I cycle off TRT, and pass the fatigue. A simple test with Liposomal Glutathione + B5 (Pantethine) at around, 250mg, or even recommend lower? Raising CoA, if copper is a primary contributor to my issue, I would assume I would see some slightly improvement relatively soon (?)

From a diet perspective would things that chelate copper be beneficial?
Thanks again, both of you.

 

[bruschi11]

That's correct, sexual function/physical attributes don't seem to be affected by TRT on or off. Just mood/energy plummets.
Once I cycle off TRT, and pass the fatigue. A simple test with Liposomal Glutathione + B5 (Pantethine) at around, 250mg, or even recommend lower? Raising CoA, if copper is a primary contributor to my issue, I would assume I would see some slightly improvement relatively soon (?)

From a diet perspective would things that chelate copper be beneficial?
Thanks again, both of you.

No liposomal glutathione. Don’t even worry about chelating copper through diet. This is more a metabolic copper utilization issue than actual cu toxicity.

Copper should be a good guy in all this. And you can make it one.

Sure try even 50-100mg of Pantethine or pantothenic acid. Or small bits of both to begin. This could put demand on biotin, b2, b12, zinc, manganese. A little acetyl carnitine could be helpful. But don’t worry about these yet.

Gbold did amazing things fixing himself. But I think he needed to tell us back then…. “Learn the Krebs cycle, learn methylation. I don’t care if you weren’t born to do these things or don’t like it. You have a chance to live a full life again. Learn the things I learned.”

That’s what I would say. My life is floating away because I didn’t learn these things when I was very functional and had a life. I just needed a little nutrient support and kill a few bugs in my system.

What happened it me in late ‘19/ early 20 was because of stupidity. Went overboard feeding crazy amounts of nutrients many I did not need. Didn’t kill the bug until I was dysregulated. Killing the bug (babesia) dysregulated me more. And I get into a gigantic hole. Nearly saved my life in late 2020 (with low dose approach) but again… was not educated enough. Made some great decisions but didn’t learn how to adjust come 2021 when they needed to be taken.

If you can find a biofeedback practitioner nearby (you in the states?). This could really help. So you can track what’s happening. Often.

I’m realizing also my big mistake was high dose nutrients throwing a bunch at a time. I got the wrong person involved. A woman that was sick and needed heavy nutrient methylation support. And that’s what she did with Me. And look at her? 3 years later we’re still in touch and she’s searching for straws for her own woes still. And her approach really contributed to me really falling off a Cliff.

Most of us men don’t need that. For instance I saw a guy in the Peat forum controlling his PFS with like 5mg of b2 in the morning and had a full life with that approach.

The goal though is to regulate and TAKE NOTHING. Or very minimal supplemental support.

The other goal, is to, as an adult with these issues… have an understanding of the things you’re utilizing. What can they offset and why? Be prepared to make adjustments.

You can Pm me if you want more direct help. I see a case like yours and I see “dude has a full life ahead of him. And relatively soon. If he takes the right path.” And honestly 90-95% of guys with pfs I believe are same way. Ya it might take a year or 2 for full recovery where you don’t need any supps. But to honestly shouldn’t be that far away from a good life.

And you shouldn’t need crazy things like testosterones of the worlds. You’re making hormones! You just have to allow your body to use them more correctly!!