Could Pregnenolone be the reason why I feel bad on TRT? (estrogen antagonism?)

[fasoracetam]

High glutamate and brain excitation plays a big role in those.

its not glutamate either as even very strong gabaergics like high dose benzos, GHB, alcohol, phenibut etc failed to eliminate these thoughts.
I tried almost everything relating dopamine, serotonin, ,glutamate, cbd,, trying to fix "deficiencies" by using minerals, amino acids, vitamins.

I tried so much things and couldnt find anything that worked. not even high dose quetiapine (an atypcal antipsychotic) could help, which is common for menopause women with low e2),.

I literally ran out of ideas what could it be, started to think that scratched off teflon in my pan could have caused neurotoxicity or stupid thoughts like that lol.
Or that it was a long drawn out Gaba-b downregulation withdrawal, cause it literally feels like that. but thats not possible.

testosterone gel worked in a matter of 3 days when nothing else worked, not even hardcore meds/drugs

 

[Hans]

When I have high e2 symptoms (flushed oily skin, itchy chest, strong serotonergic feeling, complete abscence of anhedonia, even euphoria, high libido) all of my problems are gone. while not an ideal state, its the completete opposite of how I feel now and def way better.

None of those are specifically related to estrogen. Flushed skin is due to CO2 and blood flow. T and DHT promote vasodilation.
What would you describe as serotonergic feeling?
Low serotonin and high dopamine creates euphoria and high libido.
T and DHT promote dopamine.

I'm not disqualified your experience, it's just impossible to say that those benefits are due to estrogen if you use T unless you have done tests that show that your thyroid remained the same, your T and DHT remained the same and only E went up.

 

[5a-DHP]

The issue here revolves entirely around your misunderstanding of the role that estrogen assumes within human physiology.
Your idea of 'low' and 'high' E2 symptoms are based entirely upon that perpetuated by the TRT community - I know so because I've seen the same falsehoods repeated over and over for close to ten years now.
Your view of estrogen as a hormone is so warped from ours here that there's nothing we can tell you that will change your mind. I'm not even sure why you bothered making a thread considering you're entirely unreceptive to anything that contradicts what you've already connived yourself is occurring.
I would recommended re-reading the advice that @Hans has given you.

 

[Hans]

its not glutamate either as even very strong gabaergics like high dose benzos, GHB, alcohol, phenibut etc failed to eliminate these thoughts.
I tried almost everything relating dopamine, serotonin, ,glutamate, cbd,, trying to fix "deficiencies" by using minerals, amino acids, vitamins.

I tried so much things and couldnt find anything that worked. not even high dose quetiapine (an atypcal antipsychotic) could help, which is common for menopause women with low e2),.

I literally ran out of ideas what could it be, started to think that scratched off teflon in my pan could have caused neurotoxicity or stupid thoughts like that lol.
Or that it was a long drawn out Gaba-b downregulation withdrawal, cause it literally feels like that. but thats not possible.

testosterone gel worked in a matter of 3 days when nothing else worked, not even hardcore meds/drugs

Frontiers | Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression

Human and animal studies suggest an intriguing link between mitochondrial diseases and depression. Although depression has historically been linked to altera...

www.frontiersin.org

"In fact, ATP reduction and its relation to oxidative stress have been linked not only to depression (detailed below), but also to psychotic disorders"

T and DHT are highly protective to the mitochondria and promote BDNF and neurogenesis.

 

[shine]

@fasoracetam Okay, got it. Was asking because certain pregnenolone metabolites that go down the 5-beta pathway can be NMDA antagonists (pregnanolone sulphate as an example), and your symptoms sound like NMDA dysfunction. You might be doing better with excitatory neurosteroids like DHEA/DHEA-S or with unopposed E2 from the TRT. You could also try out TMG, trimethylglycine, also known as betaine, which protects from the psychotomimetic effects of ketamine (an NMDA antagonist).

 

[fasoracetam]

I tried targeting NMDA too, didnt work either.
I just dont get why everyones trying to convince me that its everything BUT estradiol.

What chance is it, that everything failed, everything besides Testosterone which converts to estradiol, which causes the exact same symptoms everyone on the planet gets with low estradiol.


It doesnt make any sense. I managed to relief the obsessive thoughts/psychosis by just injecting an extra booster dose of testosterone for fast aromatization a month ago. And its not the testosterone that reliefs psychosis (rather can CAUSE it). DHT doesnt help psychosis either. They would worsen it. Its definitely low E2, I had more than 8 months to test out everything and nothing besides testosterone worked, And i know for a fact that its not the testosterone itself, since I had the same symptoms with 700-1000 ng/dl test. and its not the DHT either since it would worsen psychosis due to dopaminergic transmission. So for me, its only e2 left, which has, according to medical literature 99% of the same symptoms i experience when deficient.

Okay I get it, no one believes me, thanks for your time to answer anyways

 

[Hans]

I tried targeting NMDA too, didnt work either.
I just dont get why everyones trying to convince me that its everything BUT estradiol.

What chance is it, that everything failed, everything besides Testosterone which converts to estradiol, which causes the exact same symptoms everyone on the planet gets with low estradiol.


It doesnt make any sense. I managed to relief the obsessive thoughts/psychosis by just injecting an extra booster dose of testosterone for fast aromatization a month ago. And its not the testosterone that reliefs psychosis (rather can CAUSE it). DHT doesnt help psychosis either. They would worsen it. Its definitely low E2, I had more than 8 months to test out everything and nothing besides testosterone worked, And i know for a fact that its not the testosterone itself, since I had the same symptoms with 700-1000 ng/dl test. and its not the DHT either since it would worsen psychosis due to dopaminergic transmission. So for me, its only e2 left, which has, according to medical literature 99% of the same symptoms i experience when deficient.

Okay I get it, no one believes me, thanks for your time to answer anyways

Did you use plain DHT before vs T?

 

[Zsazsa]

This forum is the wrong place to debate low estradiol issues

 

[solothesensei]

O

I tried targeting NMDA too, didnt work either.
I just dont get why everyones trying to convince me that its everything BUT estradiol.

What chance is it, that everything failed, everything besides Testosterone which converts to estradiol, which causes the exact same symptoms everyone on the planet gets with low estradiol.


It doesnt make any sense. I managed to relief the obsessive thoughts/psychosis by just injecting an extra booster dose of testosterone for fast aromatization a month ago. And its not the testosterone that reliefs psychosis (rather can CAUSE it). DHT doesnt help psychosis either. They would worsen it. Its definitely low E2, I had more than 8 months to test out everything and nothing besides testosterone worked, And i know for a fact that its not the testosterone itself, since I had the same symptoms with 700-1000 ng/dl test. and its not the DHT either since it would worsen psychosis due to dopaminergic transmission. So for me, its only e2 left, which has, according to medical literature 99% of the same symptoms i experience when deficient.

Okay I get it, no one believes me, thanks for your time to answer anyways

OP, I believe you. For what it's worth, I have probably spent more time experimenting with actual HRT protocols than many theoretical experts so I think I can reconcile both sides. You are absolutely right that DHT can worsen psychosis too.

Have you tried simply adding DHEA to counteract the seemingly low e2 side effects you get from preg? I have gotten many guys with low e2 test results to try it, and they feel much better once they dial in the dosage.

Alternatively, why not increase the testosterone dose to an extent that offsets the negative preg sides?

 

[solothesensei]

Serum estradiol is not a good measure of systemic estrogen status in men. The estrogens are paracrine hormones, meaning they're produced and used in their tissue of origin without ever entering serum. Accordingly, serum estradiol - especially in a man not on exogenous hormones - tells you absolutely nothing about the level in the tissue; if you have low testosterone, the odds you have elevated tissue estrogen are extrodindarly high.

Tissue-bound estrogen in aging

Serum estradiol is primarily a reflection of intratesticular aromatization, which will be low if testosterone production is low. Again, that isn't a reflection of that in the tissue, nor the systemic estrogen load.

Respectfully my friend I would like to ask - you may be theoretically right that serum estradiol is not a good measure of systemic estrogen status, but surely you might admit there is some value in it?

If I feel good when my serum e2 is 27pg/ml and I feel terrible when my serum e2 is 17pg/ml, and this result has been consistent over many years, aren't those figures at least a useful proxy for the ultimate measure of wellbeing?

 

[5a-DHP]

OP, I believe you. For what it's worth, I have probably spent more time experimenting with actual HRT protocols than many theoretical experts so I think I can reconcile both sides.

For what it's worth, I've been on TRT - as well as having experimented with thyroid, corticoids, synthetic androgens, GH, peptides, etc - for closing in on ten years - I'm not a "theoretical expert". Not that I consider myself, or would ever be pretentious enough to identify as, an actual 'expert'.

If I feel good when my serum e2 is 27pg/ml and I feel terrible when my serum e2 is 17pg/ml, and this result has been consistent over many years, aren't those figures at least a useful proxy for the ultimate measure of wellbeing?

Sure, It offers some relatively useful insight; however, from a physiological perspective, said change in serum is accompanied by an enormous degree of change to the system as a whole. With that considered, how, exactly, can subjective changes that reflect system-level biology be attributed entirely to a small change in the serum level of a paracrine hormone?

 

[solothesensei]

For what it's worth, I've been on TRT - as well as having experimented with thyroid, corticoids, synthetic androgens, GH, peptides, etc - for closing in on ten years - I'm not a "theoretical expert". Not that I consider myself, or would ever be pretentious enough to identify as, an actual 'expert'.

Sure, It offers some relatively useful insight; however, from a physiological perspective, said change in serum is accompanied by an enormous degree of change to the system as a whole. With that considered, how, exactly, can subjective changes that reflect system-level biology be attributed entirely to a small change in the serum level of a paracrine hormone?

Very interesting, how was your experience with synthetic androgens? I presume you're referring to things like mesterolone and drostanolone? Tying this to OP's topic, I have tried these and found a noticeable estrogen antagonism effect, and I know I've taken too much when I start to get painful joints (among other symptoms).

You're absolutely right, since estrogen is a paracrine hormone, there will be many intermediate steps in its broad mechanism of action that can almost never be fully elucidated. Nonetheless, there's value in drawing insight from its serum changes. We both agree on that and we're not in contradiction at all.

 

[BestSinceDAYONE]

Yes cause everything leads to E2 in terms of symptoms and symptom relief. If low T caused a deficiency in neurosteroids then I wouldnt feel the same right now, cause I took a large dose of a neurosteroid precursor and have additional high T levels right now.

In the past I had supressed testosterone from SARMS (which leads to low e2 and low shbg) which was the exact same feeling. I doubt DHT plays any role as it doesnt regulate how the body holds water (dehydration) and I never heard of it being anti-psychotic like estradiol.

I know no one believes me but I lived in that state of hell for almost a year and experimented with a shitton of supps and meds and drugs. Its definitely not GABA-antagonism either, as with Low T, I tried taking benzos in high dose, (40mg diazepam without any tolerance) and the obsessive thoughts were still there. even though i was really heavy "benzo-drunk"

kratom, real opiates, benzos, nothing could relief my symptoms. ONLY trt did, in a matter of 4 days my life changed.

not even 700++ total test, maybe even up 1000 could relief my symptoms, so it wasnt T or DHT either. only thing left is estradiol.

Obsessive, paranoid thoughts, psychosis is all documented with low estradiol, and in my experience and according to medical literature it must be exactly that

Yeah when ppl take arimidex they get joint pain and end up feeling like ****. Why do all the trt gurus say estrogen is important.

Also when I took ostarine, funny enough my hair actually came back

 

[TheBeard]

Why would you feeling bad on pregnenolone have anything to do with e2 antagonism, when there is 99% chance it's the pregnenolone or progesterone action itself?

When you see a hoof print on the ground, you look for a horse first, not a zebra.

 

[sladerunner69]

Pregnenolone, nor progesterone, will crash serum estradiol in a man on TRT.
Also, despite what the TRT community will tell you: none of the symptoms you listed are caused by low estradiol.
That community is extrodindarly narrow minded with no real scope of system level biology, which in-turn leads to every single symptom or side effect being attributed to low or high E2. Doesn't work like that in reality.
Your side effects are likely from pregnenolone itself and/ or it's downstream metabolites.

Despite the TRT community being too pro-estrogen, those symptoms are indeed classic low estrogen. I, along with many others, have been led there by the initial euphoria of pregnenelone/progesterone doses but overtime it drives estrogen too low. He is likely better off taking small doses of allopregnenlone or, as your namesake, 5a-DHP, because these will likely not have as strong an estrogen inhibiting effect.

Yes cause everything leads to E2 in terms of symptoms and symptom relief. If low T caused a deficiency in neurosteroids then I wouldnt feel the same right now, cause I took a large dose of a neurosteroid precursor and have additional high T levels right now.

In the past I had supressed testosterone from SARMS (which leads to low e2 and low shbg) which was the exact same feeling. I doubt DHT plays any role as it doesnt regulate how the body holds water (dehydration) and I never heard of it being anti-psychotic like estradiol.

I know no one believes me but I lived in that state of hell for almost a year and experimented with a shitton of supps and meds and drugs. Its definitely not GABA-antagonism either, as with Low T, I tried taking benzos in high dose, (40mg diazepam without any tolerance) and the obsessive thoughts were still there. even though i was really heavy "benzo-drunk"

kratom, real opiates, benzos, nothing could relief my symptoms. ONLY trt did, in a matter of 4 days my life changed.

not even 700++ total test, maybe even up 1000 could relief my symptoms, so it wasnt T or DHT either. only thing left is estradiol.

Obsessive, paranoid thoughts, psychosis is all documented with low estradiol, and in my experience and according to medical literature it must be exactly that

You see, what I ahve come to realize through a decade of trial and error with androgens and peating is that we are seeking is the proper androgen:estrogen ratio. When you are peating and keeping estrogen very low via vitamins and pufa avoidance and high thyroid and so on, you do not need much testosterone or extra androgens to feel well. The feeling is calm, but focussed, relaxed but with plenty of mental energy to be creative and productive. The libido is not particularly high, but is still present. When one decides they want to take steps to increase androgens, such as taking DHEA, testosterone etc in order to acheive a more physical, "masculine" kind of energy, they can that, but will need to balance the increased androgens with estrogen and cortisol. Not only do these stress hormones provide key strucural functions like bone, joint and skin health, they also stimulate the nervous system and musculature. Further, it has been observed that the presence of estrogen itself activates and "sensitizes" androgen receptors, making the TRT more effective. Depending on the volume of testosterone you are taking, it is probably unwise to take large amounts of aromatase inhibitors and you may even consider taking estradiol cream. Taking TRT is anti-peat anyways, and is probably not a good idea if you are concerned with longevity (it can be fun though, I know). When Peat takes testosterone he used only a few mg at a time.

 

[solothesensei]

these are all things that can also play a part in this, but it doesnt answer why testosterone (plus its aromatization) reliefed these symptoms for me when I was low T.
Back then I have never heard of pregnenolone
like you said before, preg-s' gaba antagonism could adds to the anxiety, but idk I cant prove it to anyone, but the feeling of Low E2 is very easy to idenitify for me.

When I have high e2 symptoms (flushed oily skin, itchy chest, strong serotonergic feeling, complete abscence of anhedonia, even euphoria, high libido) all of my problems are gone. while not an ideal state, its the completete opposite of how I feel now and def way better.

If I had Estradiol creme or such i would bathe in it right now

Why don't you get some estradiol cypionate and administer something like 50-100mcg to test your hypothesis that it's really the low E2?

Personally I am also co-administering E2 with my TRT and I feel better than I've ever had for years. In my case, I abused aromasin for a long time which seems to have permanently reduced my aromatase enzymes.

 

[sladerunner69]

Why don't you get some estradiol cypionate and administer something like 50-100mcg to test your hypothesis that it's really the low E2?

Personally I am also co-administering E2 with my TRT and I feel better than I've ever had for years. In my case, I abused aromasin for a long time which seems to have permanently reduced my aromatase enzymes.

Where does one acquire E2 as opposed to just estradiol or something like that? Does the estrogen have any negative effects?

 

[solothesensei]

Where does one acquire E2 as opposed to just estradiol or something like that? Does the estrogen have any negative effects?

You can acquire estradiol valerate, enanthate or cypionate if you search a bit on the MtF transgender forums.

It's all about getting the right balance. At the dose I'm administering (200mcg every 2 days) not at all. If I accidentally exceed the syringe marker by a few units, I get a funny feeling in my nipples and get too emotional for a day or two.

 

[sladerunner69]

You can acquire estradiol valerate, enanthate or cypionate if you search a bit on the MtF transgender forums.

It's all about getting the right balance. At the dose I'm administering (200mcg every 2 days) not at all. If I accidentally exceed the syringe marker by a few units, I get a funny feeling in my nipples and get too emotional for a day or two.

I see. I have been using strong estrogen inhibitors for years and have recently noticed that consuming soy milk or soy sauce makes me feel markedly better very quickly. What kind of beneficial effects do you get? I was considering using an estrogen cream like the following: Amazon product ASIN B08TH379G1View: https://www.amazon.com/gp/product/B08TH379G1/ref=ox_sc_act_title_3?smid=A1OCX45XAJB8MD&psc=1

 

[solothesensei]

I see. I have been using strong estrogen inhibitors for years and have recently noticed that consuming soy milk or soy sauce makes me feel markedly better very quickly. What kind of beneficial effects do you get? I was considering using an estrogen cream like the following: Amazon product ASIN B08TH379G1View: https://www.amazon.com/gp/product/B08TH379G1/ref=ox_sc_act_title_3?smid=A1OCX45XAJB8MD&psc=1

Definitely a big improvement in mood, reduction in anxiety, better pumps in the gym and higher libido.

Estradiol seems to be generally villainized a lot, like how serotonin is in this sub. As with everything, there is simply a sweet spot to be achieved - not too high and not too low.