Pregnenolone Is A (functional) Estrogen Antagonist

haidut

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About 2 years ago I posted a thread on the antagonism of pregnenolone to estrogen.
Pregnenolone Is An Estrogen Antagonist

That claim was from a study, which itself referenced an old French study from 1950. I asked @burtlancast to find it and he was able to trace it to a hardcopy of the French journal (in French) kept at the National Library of Medicine (NLM) located on the NIH campus, a few miles from where I live. So, I hopped in a car and went to get it. See attached study, for those of you who can read it in French. For the rest, below is a rough translation provided by Burt and Google Translate.
So, it looks like 250mg daily dose of pregnenolone was able to antagonize the effects of the endogenous estrogens estradiol and estrone but was ineffective against the more potent synthetic estrogens ethinyl-estradiol and stilbestrol (DES). However, increase the dose of pregnenolone to 500mg was able to completely antagonize the effects of those synthetic estrogen as well.
The only thing that is not clear from the study is whether the pregnenolone was given on a daily basis with the estrogens or if it was a one-time dose after the estrogen treatment course was complete. My French is abysmal so maybe @burtlancast or another French speaker can cast more light on this??
If somebody wants to send to Ray he will probably appreciate it, and I think he said he now speaks French after loading up on thiamine before the language course :):

"...In previous work [1], we reported a series of observations, performed in ovariectomized women, showing that delta-5-pregnenolone could inhibit the endometrial growth effect of estradiol and estrone. This inhibitory action was not exercised in regards to the stilboestrol and ethinyl estradiol when 250mg of pregnenolone was administered every twenty-four hours together with 1mg of stilboestrol, or 25mcg of ethinyl estradiol. This discrepancy (with earlier results in [1]) seemed to us, at first glance, to have to be a question of dosage. This hypothesis proved to be correct, at least as far as relating to ethinyl estradiol.

"...Subject 48 years old, castrate for ten years and regularly submitted since then to treatment with sex hormones. From the April 16, 1949, seven days after the end of an effective treatment, 25 gamma ethinyl estradiol, gastrointestinal, per day, with 500 milligrams of pregnenolone, by the same route."

"...Conclusion: From all this, it follows that (500mg but not 250mg) pregnenolone is able to completely inhibit the endometrial growth effect of ethinyl estradiol, as well as that of estradiol and estrone. This anti-estrogen action appears to be general and should therefore be exercised too, in all probability, against stilboestrol also. The mechanism of blood loss following treatment remains obscure; the trauma of the biopsy certainly cannot alone, explain this phenomenon."
 

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burtlancast

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The only thing that is not clear from the study is whether the pregnenolone was given on a daily basis with the estrogens or if it was a one-time dose after the estrogen treatment course was complete.

It was on every day, not an one-time.

They first administered sexual hormones replacement therapy (whatever that implies) to women with removed ovaries, then waited 7 days and began treatment every day for 2 weeks total of both 500 mg pregnenolone and 25 micrograms of éthinyl-oestradiol, and proved no estrogen stimulation signs over the endometrium appeared.

They compared it with the anterior treatment of the same subject with 25 micrograms of éthinyl-oestradiol alone, which showed clear signs of estrogen stimulation.
 

haidut

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It was on every day, not an one-time.

They first administered sexual hormones replacement therapy (whatever that implies) to women with removed ovaries, then waited 7 days and began treatment every day for 2 weeks total of both 500 mg pregnenolone and 25 micrograms of éthinyl-oestradiol, and proved no estrogen stimulation signs over the endometrium appeared.

They compared it with the anterior treatment of the same subject with 25 micrograms of éthinyl-oestradiol alone, which showed clear signs of estrogen stimulation.

Understood, thanks. What about the original treatment with 250mg pregnenolone? Is it correct that it antagonized estradiol and estrone but NOT the synthetic DES and ethinyl-estradiol?
 

burtlancast

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Yes, that's what they explained in the study.
 

haidut

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It would be interesting to find how the hell Ray's favourite pregnenolone* was produced.

* "Syntex factory in Mexico, 1984-5" Ray Peat Email Advice Depository

I wonder if that pregnenolone had some other steroid byproducts in it. Pregnenolone can oxidize over time and potentially turn into other steroids. Kind of like the impurities in the original vitamin E that Peat said were mostly responsible for the beneficial effects.
 

TreasureVibe

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It would be interesting to find how the hell Ray's favourite pregnenolone* was produced.

* "Syntex factory in Mexico, 1984-5" Ray Peat Email Advice Depository
From that link:

Q: "I want to ask you about a quote from Haidut. I remember you saying that impurities in pregnenolone are responsible for many bad reactions, but I've come to be suspicious when compounds are said to have mixed good/bad effects (like estrogen). Thanks for your time Ray, hope you have a good thanksgiving.

"In higher doses, pregnenolone not only saturates the enzymes but also seems to inhibit 3b-HSD, which is crucial for the synthesis of testosterone. Also, in lower doses pregnenolone seems to act as an agonist on the androgen receptor. Higher doses lead to mostly conversion into progesterone and as such an anti-androgenic effect. So, I found what doses in humans would provide enough pregnenolone for the beneficial effects to be observed without triggering the negative ones. While I can't divulge what that upper limit is to avoid getting copied by competitors :) I can tell you that 5mg pregnenolone per dose WHEN combined with DHEA has these beneficial effects without the negatives." -haidut"

Ray: "When I was buying pregnenolone from the Syntex factory in Mexico, 1984-5, to test its safety I ate a kilogram of it during a year, 3000 to 4000 milligrams per day. I didn’t detect any side effects at all, except that my skin, that had been sagging over my eyes and on my neck, firmed up. I know a man in his sixties who is taking a teaspoonful every day, without any bad effects."

@haidut Is pregnenolone beneficial or not for androgens and lowering/opposing estrogen?
 

haidut

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From that link:



@haidut Is pregnenolone beneficial or not for androgens and lowering/opposing estrogen?

So far, I have only received negative reports on libido and muscle tone from doses higher than 100mg daily. The anti-estrogenic effects is probably present in any dose, as pregnenolone is also an aromatase inhibitor, but for complete blockade of estrogen the 500mg+ doses seem to be needed as per the study.
https://raypeatforum.com/community/...d-androsterone-are-aromatase-inhibitors.3596/
 

Jackrabbit

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So far, I have only received negative reports on libido and muscle tone from doses higher than 100mg daily. The anti-estrogenic effects is probably present in any dose, as pregnenolone is also an aromatase inhibitor, but for complete blockade of estrogen the 500mg+ doses seem to be needed as per the study.
Pregnenolone, Progesterone And Androsterone Are Aromatase Inhibitors

I’m sorry I know this is an old thread, but was wondering if you could clarify if taking 500mg pregnenolone daily would mean you would not want to take dhea simultaneously. I believe you said in the pansterone thread that taking higher doses of pregnenolone and dhea together could result in high bp.
 
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I have found 200mg very, very helpful and it has raised my libido if anything. I'm taking some DHEA (3mg to 8mg per day) and maybe 8mg or so of progesterone too.
 

Jackrabbit

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I have found 200mg very, very helpful and it has raised my libido if anything. I'm taking some DHEA (3mg to 8mg per day) and maybe 8mg or so of progesterone too.
Ok nice, I’m assuming you haven’t had any major blood pressure increases then. That’s interesting because over 200mgs is supposed to have an anti-androgen effect, but it’s helping your libido. I’m thinking it’s boosting your progesterone, especially because you’re also taking a smallish dose of progesterone?
 

haidut

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I’m sorry I know this is an old thread, but was wondering if you could clarify if taking 500mg pregnenolone daily would mean you would not want to take dhea simultaneously. I believe you said in the pansterone thread that taking higher doses of pregnenolone and dhea together could result in high bp.

I think 100mg pregnenolone with 5mg DHEA is probably OK. Have not tried 500mg pregnenolone with DHEA but human studies with the 500mg pregnenolone showed that it boosts DHEA-S a somewhat, so if you don't need that much of a DHEA boost then maybe 500mg pregnenolone on its own would be enough.
 

invictus

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@haidut: I've read your earlier posts on pregnenolone in regards to up regulating thyroid function/weight loss. Your calculation of the animal data came to 30mg/kg. My current weight, which has been rising since 2011, is now 165(way too high at 5'5") and at 30mg/kg, I would need to take about 2400 mg, daily. I realize that studies, whether on animals or humans, can be narrow in scope, only focusing on a particular clinical aspect and those studies can conflict with other studies, looking at something else. Trying to extrapolate data and apply it to ourselves can certainly be tricky and difficult.
 

haidut

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@haidut: I've read your earlier posts on pregnenolone in regards to up regulating thyroid function/weight loss. Your calculation of the animal data came to 30mg/kg. My current weight, which has been rising since 2011, is now 165(way too high at 5'5") and at 30mg/kg, I would need to take about 2400 mg, daily. I realize that studies, whether on animals or humans, can be narrow in scope, only focusing on a particular clinical aspect and those studies can conflict with other studies, looking at something else. Trying to extrapolate data and apply it to ourselves can certainly be tricky and difficult.

Where did you see my calculations show 30mg/kg? I think that was the animal dose (mice maybe?) so in humans it would be about 2.5mg/kg.
 
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