Pregnenolone, Progesterone And Androsterone Are Aromatase Inhibitors

[energyandstruct]

I have seen some people in the forum claim that they thought pregnenolone increased their estrogen levels. According to this study, pregnenolone should in fact lower estrogen by inhibiting aromatase. Peat has already written extensively on progesterone being a known aromatase inhibitor, so that is no news:
The concentrations of pregnenolone used were not high at all - 500nM inhibited aromatase by about 25%. Perhaps ore importantly, neither pregnenolone not progesterone could be used as a substrate for aromatase - i.e. they could not be used as source material for synthesizing more estrogen. Some people on the Internet keep claiming pregnenolone or progesterone gave them immediate estrogen symptoms. Well, this study suggests that this is unlikely as neither pregnenolone nor progesterone could be used as raw materials by aromatase for making more estrogen.
Finally, the study also tested the 5-AR steroids commonly discussed on this forum - i.e. DHT, androsterone, androstanedione and androstanediol. They all inhibited aromatase in concentrations of 500nM and androsterone specifically inhibited aromatase by about 45%. A dose of about 2mg can achieve concentrations of 500nM. Another study posted in the androsterone threads showed that a twice as high concentration (1uM) inhibited aromatase by more than 90%. See attached images for more info.


FSH-induced aromatase activity in porcine granulosa cells: non-competitive inhibition by non-aromatizable androgens. - PubMed - NCBI

"...Other steroids such as pregnenolone and progesterone were inhibitory, but testosterone and diethylstilboestrol were stimulatory."

"...As shown in Fig. 3, a 100-fold increase in oestradiol production was evident in cell culture containing FSH and testosterone during induction. All the other steroids were ineffective as substrates for aromatase. Similarly, during the test period the synthesis of oestradiol was significantly (p<0.05) enhanced in cells previously exposed to testosterone (160%) or DES (25%) and FSH, when compared with that of the FSH-stimulated ones. However, the presence of pregnenolone, progesterone and DHT (during the induction) significantly (p<0.05) decreased the FSH-induced aromatization of testosterone."

"...To examine whether other 5-reduced C19 androgens also inhibit FSH-induced aromatase activity, granulosa cells were cultured for an initial induction period of 48h in the presence and absense of FSH with or without 0.5uM/L DHT, 5α-androsterone, 5α-androstane-3α,17β-diol, 5α-androstane-3α,17β-dione and 5β-androstane-3,17-dione. After the induction, the cells were incubated for an additional 6h. All the androgens tested were effective in significantly (p<0.05) reducing the aromatization of testosterone (Fig. 5). 5β-androstanedione was the most effective (57%) while DHT was the least (33%) when compared with cultures containing only FSH (Fig. 5, insert)."

Here is another study referenced by the one above, which also found the 5-AR derived steroids to inhibit aromatase, even when used in low physiological concentrations.
http://joe.endocrinology-journals.org.sci-hub.bz/content/84/3/409.long

I took pregnenolone for the second time today to address my fatigue and low cortisol. It has made me very, very irritable, seemed to increase stress hormones, and just seems overall estrogenic. Is there no way that pregnenolone can increase estrogen? i know people that have said that they were measured and that pregnenolone increased their estrogen. Is there something that prevents the dhea in your system from turning into estrogen?

the experience was not merely negative, but it was strange. At first I felt more tension/anxiety. Then i felt some mood uplift and euphoria but it didn't feel that great kinda like a drug...

And then I just started feeling irritable as ****--- way more than usual, like it feels like a physical feeling. I got in way more arguments and just feel "bitchy" for lack of a better word. This seems to be way more associated with estrogen than progesterone, in fact progesterone dropping is thought to cause irritability...

any thoughts?

it was health natura pregnenolone

 

[haidut]

I took pregnenolone for the second time today to address my fatigue and low cortisol. It has made me very, very irritable, seemed to increase stress hormones, and just seems overall estrogenic. Is there no way that pregnenolone can increase estrogen? i know people that have said that they were measured and that pregnenolone increased their estrogen. Is there something that prevents the dhea in your system from turning into estrogen?

the experience was not merely negative, but it was strange. At first I felt more tension/anxiety. Then i felt some mood uplift and euphoria but it didn't feel that great kinda like a drug...

And then I just started feeling irritable as ****--- way more than usual, like it feels like a physical feeling. I got in way more arguments and just feel "bitchy" for lack of a better word. This seems to be way more associated with estrogen than progesterone, in fact progesterone dropping is thought to cause irritability...

any thoughts?

it was health natura pregnenolone

Pregnenolone can raise allopregnanolone, which can have paradoxical effects including increased irritability and sometimes even anxiety. Check the Wiki page on allopregnanolone and its mood effects. If pregnenolone elevated estrogen it would mean it also elevated DHEA/testosterone, and the latter is not a bad thing. So, a lower dose should avoid the estrogenic effects while still upregulating androgens.

 

[Frankdee20]

I took pregnenolone for the second time today to address my fatigue and low cortisol. It has made me very, very irritable, seemed to increase stress hormones, and just seems overall estrogenic. Is there no way that pregnenolone can increase estrogen? i know people that have said that they were measured and that pregnenolone increased their estrogen. Is there something that prevents the dhea in your system from turning into estrogen?

the experience was not merely negative, but it was strange. At first I felt more tension/anxiety. Then i felt some mood uplift and euphoria but it didn't feel that great kinda like a drug...

And then I just started feeling irritable as ****--- way more than usual, like it feels like a physical feeling. I got in way more arguments and just feel "bitchy" for lack of a better word. This seems to be way more associated with estrogen than progesterone, in fact progesterone dropping is thought to cause irritability...

any thoughts?

it was health natura pregnenolone

This is common when starting, I used to get incredibly crazy from it, doses as low as ten. Now, it’s one of my favorite supplements but I take it with fuel. It can be constipating at 20mg, and will give insomnia at that dose.

 

[energyandstruct]

Pregnenolone can raise allopregnanolone, which can have paradoxical effects including increased irritability and sometimes even anxiety. Check the Wiki page on allopregnanolone and its mood effects. If pregnenolone elevated estrogen it would mean it also elevated DHEA/testosterone, and the latter is not a bad thing. So, a lower dose should avoid the estrogenic effects while still upregulating androgens.

hmm ok, it gets hard to measure out powder in doses lower than i was taking, so I may have to figure out volumetric dosing. would vegetable glycerin be a good solvent?

 

[energyandstruct]

How come ray says doses up to 1000 mg are fine, if it raises allo pregnenolone?

 

[haidut]

hmm ok, it gets hard to measure out powder in doses lower than i was taking, so I may have to figure out volumetric dosing. would vegetable glycerin be a good solvent?

Steroids are lipophillic and do not dissolve well in glycerin, especially pregnenolone which is hard to dissolve in anything really.

 

[energyandstruct]

Steroids are lipophillic and do not dissolve well in glycerin, especially pregnenolone which is hard to dissolve in anything really.

what about liquefied (heated) coconut oil

 

[haidut]

what about liquefied (heated) coconut oil

While heated they will dissolve but then will start precipitating once it cools off. At least pregnenolone and androsterone will.

 

[energyandstruct]

While heated they will dissolve but then will start precipitating once it cools off. At least pregnenolone and androsterone will.

damn, there are really no good solvents for pregnenolone available easily/cheaply? there's no way I can get an accurate enough scale to dose these very small doses

 

[haidut]

damn, there are really no good solvents for pregnenolone available easily/cheaply? there's no way I can get an accurate enough scale to dose these very small doses

Well, you can probably still dissolve 10mg-15mg per ml of oil. It should be enough to use as oral supplement.

 

[CaliforniaKat]

I took pregnenolone for the second time today to address my fatigue and low cortisol. It has made me very, very irritable, seemed to increase stress hormones, and just seems overall estrogenic. Is there no way that pregnenolone can increase estrogen? i know people that have said that they were measured and that pregnenolone increased their estrogen. Is there something that prevents the dhea in your system from turning into estrogen?

the experience was not merely negative, but it was strange. At first I felt more tension/anxiety. Then i felt some mood uplift and euphoria but it didn't feel that great kinda like a drug...

And then I just started feeling irritable as ****--- way more than usual, like it feels like a physical feeling. I got in way more arguments and just feel "bitchy" for lack of a better word. This seems to be way more associated with estrogen than progesterone, in fact progesterone dropping is thought to cause irritability...

any thoughts?

it was health natura pregnenolone

I know this thread is older, but I am hoping someone may still answer. All my hormones/dhea and a salivary cortisol test are low ( but barely within the 'normal' range). My temps are still low, 97.0 waking on average and 98.0 to 98.2 in the afternoon. I take 2 grains NDT. Test T3 and T4 are in the low end of the normal range. How much would pregnenolone help with the low cortisol and hormones? Small dose or large dose?

 

[energyandstruct]

I know this thread is older, but I am hoping someone may still answer. All my hormones/dhea and a salivary cortisol test are low ( but barely within the 'normal' range). My temps are still low, 97.0 waking on average and 98.0 to 98.2 in the afternoon. I take 2 grains NDT. Test T3 and T4 are in the low end of the normal range. How much would pregnenolone help with the low cortisol and hormones? Small dose or large dose?

I don't think saliva cortisol tests are very accurate

 

[Frankdee20]

I know this thread is older, but I am hoping someone may still answer. All my hormones/dhea and a salivary cortisol test are low ( but barely within the 'normal' range). My temps are still low, 97.0 waking on average and 98.0 to 98.2 in the afternoon. I take 2 grains NDT. Test T3 and T4 are in the low end of the normal range. How much would pregnenolone help with the low cortisol and hormones? Small dose or large dose?

Pregnenalone does lower ACTH and cortisol. However, perhaps it can raise it via conversion

 

[haidut]

I know this thread is older, but I am hoping someone may still answer. All my hormones/dhea and a salivary cortisol test are low ( but barely within the 'normal' range). My temps are still low, 97.0 waking on average and 98.0 to 98.2 in the afternoon. I take 2 grains NDT. Test T3 and T4 are in the low end of the normal range. How much would pregnenolone help with the low cortisol and hormones? Small dose or large dose?

I would ask the doctor to do both AM and PM blood test for cortisol. It means 2 draws in the same day but when they place the canula in the morning they can leave it inside and then in the afternoon can just extract more blood without another puncture. Some people have low cortisol at one point in the day and elevated 12 hours later. Only the blood test for both AM and PM can show reliably if there is an issue. Saliva tests measure mostly local tissue hormone concentrations. Still useful but not as good as the blood test when it comes to cortisol.

 

[Mauritio]

Just want to note. I wrote earlier about pregnenolone raising estrogen etc and making me feel like rubbish.

Well, I have trialed preg again. As usual it raised my temps, energy etc for the first few days. Then I fell back into the bloated, cold, high estrogen effects i get from preg. However, i realized if preg doesnt directly raise estrogen something else was doing it.

What was happening was preg was raising my metabolism. This was causing a release of PUFA's as my detox systems etc ramped up. The increased PUFA's then caused high estrogen, serotonin, low metabolism etc.

After supplementing with a high dose of vitamin E, aspirin, coconut oil etc., my temperatures started to come back up and my distended stomach started to shrink back down.


So, the lesson from that is, increasing your metabolism can cause an increase in circulating PUFA's making you worse off than when you started..

High dose aspirin can also trigger stress symptoms. Vitamin E is unique among these as it inhibits lipolysis (through its opposition to estrogen), and can inactivate the PUFA already in the bloodstream. So, vitamin E improve metabolism by lowering fat oxidation. I don't think it has direct effects on mitochondria like aspirin and caffeine do. Coconut oil improves metabolism acutely by increasing the SFA/PUFA ration in blood and displacing the PUFA from the cell mitochondria in the beta oxidation process. Since it can go directly inside the mitochondria and it needs no special transport, the cell prefers to burn it and leave PUFA for last or actually store it. Some fats in cocobut oil have uncoupling effect but not much to match aspirin and caffeine. So, there are different ways to improve metabolism but caffeine and aspirin are thyroid mimetics and just like a large dose of thyroid will trigger s stress response when energy stores run out.

Interesting. I have also found even a few mg of Preg caused supposed estrogenic or cortisol symptoms . I felt mostly great at daytime and looked more androgenic/muscular but couldn't sleep at night . The "estrogen"-symptoms were taken care of by 5adhp (hair loss) , but still couldn't find a way to fall asleep.
So in the light of this just releasing PUFA and the hole stress cascade down the road it all makes sense. So i am going to try taking a few mg of Preg every second day again with things as 5adhp, coconut oil ,and magnesium in my arsenal .

 

[tankasnowgod]

Interesting. I have also found even a few mg of Preg caused supposed estrogenic or cortisol symptoms . I felt mostly great at daytime and looked more androgenic/muscular but couldn't sleep at night . The "estrogen"-symptoms were taken care of by 5adhp (hair loss) , but still couldn't find a way to fall asleep.
So in the light of this just releasing PUFA and the hole stress cascade down the road it all makes sense. So i am going to try taking a few mg of Preg every second day again with things as 5adhp, coconut oil ,and magnesium in my arsenal .

Those are both fantastic points. Based on the Haidut/Roddy livestream and Peat interview with Jodelle, I got really interested in Pregnenolone again. Lot's of just fantastic research, but a lot of people on this forum have reported problems. The liberation of PUFA and/or lack of fuel (sugar/carbs) pretty much explain every issue I have seen from people. So, I'll certainly be ready with a Pepsi and Vitamin E.

I wonder if there is also a phenomenon like the "Low Carb Flu," but in reverse. Going low carb, you have issues as you ramp into a cortisol metabolism. With Preg/Thyroid/Aspirin and such, it's reverse, backing out of a cortisol metabolism and into thyroid metabolism. During the shifting over, either way, you may get periods of fatigue and lethargy, as you don't have enough of either the stress or thyroid hormones to run at the level you are used to running at.

 

[TeaRex14]

Those are both fantastic points. Based on the Haidut/Roddy livestream and Peat interview with Jodelle, I got really interested in Pregnenolone again. Lot's of just fantastic research, but a lot of people on this forum have reported problems. The liberation of PUFA and/or lack of fuel (sugar/carbs) pretty much explain every issue I have seen from people. So, I'll certainly be ready with a Pepsi and Vitamin E.

I wonder if there is also a phenomenon like the "Low Carb Flu," but in reverse. Going low carb, you have issues as you ramp into a cortisol metabolism. With Preg/Thyroid/Aspirin and such, it's reverse, backing out of a cortisol metabolism and into thyroid metabolism. During the shifting over, either way, you may get periods of fatigue and lethargy, as you don't have enough of either the stress or thyroid hormones to run at the level you are used to running at.

I respond very well to pregnenolone. Currently I've stopped because I'm reusing thyroid again, I don't take the two together. It makes me very hot feeling. But a combination of preg and aspirin is very effective. Excellent workout supplement stack as well, for me anyways. It does require a good amount of dietary sugar.

 

[Regina]

Those are both fantastic points. Based on the Haidut/Roddy livestream and Peat interview with Jodelle, I got really interested in Pregnenolone again. Lot's of just fantastic research, but a lot of people on this forum have reported problems. The liberation of PUFA and/or lack of fuel (sugar/carbs) pretty much explain every issue I have seen from people. So, I'll certainly be ready with a Pepsi and Vitamin E.

I wonder if there is also a phenomenon like the "Low Carb Flu," but in reverse. Going low carb, you have issues as you ramp into a cortisol metabolism. With Preg/Thyroid/Aspirin and such, it's reverse, backing out of a cortisol metabolism and into thyroid metabolism. During the shifting over, either way, you may get periods of fatigue and lethargy, as you don't have enough of either the stress or thyroid hormones to run at the level you are used to running at.

Cool. And I agree. Kindof turning around the Queen Mary at harbour.

 

[Mauritio]

Those are both fantastic points. Based on the Haidut/Roddy livestream and Peat interview with Jodelle, I got really interested in Pregnenolone again. Lot's of just fantastic research, but a lot of people on this forum have reported problems. The liberation of PUFA and/or lack of fuel (sugar/carbs) pretty much explain every issue I have seen from people. So, I'll certainly be ready with a Pepsi and Vitamin E.

I wonder if there is also a phenomenon like the "Low Carb Flu," but in reverse. Going low carb, you have issues as you ramp into a cortisol metabolism. With Preg/Thyroid/Aspirin and such, it's reverse, backing out of a cortisol metabolism and into thyroid metabolism. During the shifting over, either way, you may get periods of fatigue and lethargy, as you don't have enough of either the stress or thyroid hormones to run at the level you are used to running at.

I think you are spot with your lack of fuel. Which also comes down to low glycogen stores!!
But then again: why are glyocogen stores low?
I think in my case it comes down to a chronic bacterial infection causing high stress hormones ,bad liver function and low thyroid

 

[SonOfEurope]

Pregnenolone disrupts my sleep if I take it at night.

That's how it works unless the dose is very low as in under 20mg for two reasons:

1) Conversion to Progesterone which squeezes Estrogen out - momentary increasing sensitivity.

1) Massive Neuro-steroid Shift.

Take 800mg with a full macronutrient meal one morning and bring it down to 50mg daily and sleep should be great. The body eventually gets used to redirecting it coherently to downstream Progesterone and sex steroids.