Pregnenolone Metabolite Lowers Cortisol By 60%

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haidut

haidut

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Fetch said:
post 103558 haidut if you're still following this thread. Do you know if there is any difference between oral or topical pregnenolone like there is for DHEA? I have seen you mention using both forms. I've only been using topical but oral would be very convenient.

Oral pregnenolone has higher chance of staying as pregnenolone, even if some it metabolizes into downstream hormones. Topical pregnenolone will metabolize almost completely before reaching the blood stream. So, topical pregnenolone will metabolize into whatever the local tissue needs, but most likely progesterone and some androgens.
 
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Fetch

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haidut said:
post 103560 Fetch wrote:
Source of the post haidut if you're still following this thread. Do you know if there is any difference between oral or topical pregnenolone like there is for DHEA? I have seen you mention using both forms. I've only been using topical but oral would be very convenient.


Oral pregnenolone has higher chance of staying as pregnenolone, even if some it metabolizes into downstream hormones. Topical pregnenolone will metabolize almost completely before reaching the blood stream. So, topical pregnenolone will metabolize into whatever the local tissue needs, but most likely progesterone and some androgens.


Thanks as always
 
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treelady

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Peata said:
post 103547
treelady said:
post 103544 I've been at the 50mg/day Pregnenolone level and have the facial hair problem. I haven't stopped taking it because I read all this great stuff about it but I am tired of plucking chin hair...I'm going off it. I don't know why I would need it anyway since I take lots of Progest-E.

Facial hair only since using pregn. or did you have a problem with it before? Just curious.

What has your dosing history of pregn. been like?

Again just wondering since I may experiment with it again sometime soon.

I didn't have facial hair before oral Pregnenolone.
Dosing history: I had tried 50mg in the morning and 50mg evening for a while and the facial hair started. I went off it and things seemed better. I went back on at 50mg/day and the problem came back. :(
 
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ilovethesea

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Peata said:
post 103546

I also used to take spironolactone and thought the effect from it was due to regulating aldosterone. But maybe that is just looking at it from another side of the same coin. I never had any success with saw palmetto either. I haven't experimented with preg. lately but it's good to know you are finding success with it for pms acne. That's been one of my problems. I'll look forward to updates from you on it. Are you taking 400 mg. daily, certain time of day, or just during last half of cycle?

I've experimented with 200mg in the 1st two weeks of my cycle when androgens are lower, but I think my skin is best and I feel best when I take the 400mg every day throughout the month. It's the most preventative. Doesn't seem to matter what time of day but usually I take it at night. I think there is a bonus relaxation effect. I am not too stressed but it seems to help with stress.

I think I must need tons of it as my thyroid is so weak and I still have lots of hypo issues, including some eye asymmetry/enlargement that is bothering me. I don't want to go to the doctor because they will say it is Graves and the last thing I need is to be told I'm getting too much thyroid! I know pregnenolone is what Ray said to do for that.
 
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Agent207

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haidut said:
Those crashes/hangovers are most likely due to two main issues - lower cortisol and higher pogesterone/allopregnanolone. The crashes suggest metabolism is low, since after lowering cortisol the body turns to thyroid for energy and if there is none/little then you crash.
Peat has written about the "drunk" and hangover feelings from progsterone. Allopregnanolone gives people the same feeling. Google both hormones and the Wikipedia page for both describes these effects. So, pregnenolone is actually giving you a pretty good signal in this case - a signal that you are still mostly running on stress hormones and you need to increase thyroid output or lower FFA that may be blocking repiration even in the presence of normal thyroid.
Just my 2c.

Have some doubts about this,

1. High progesterone and low cortisol; couldn't this be a warning for checking if the problem may rely on any of the enzymes implicated in the Progesterone-Cortisol pathway underworking and constipating the conversion? 17a, 21 or 11b-Hydroxylase?

2. When cortisol is deficient, wouldn't be wise to correct this first on the root, rather than force an increase of thyroid in a cortisol insufficiency scenario?

3. Is cortisol a stress hormone, or anti-stress hormone actually?
 
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Agent207 said:
post 118807
haidut said:
Those crashes/hangovers are most likely due to two main issues - lower cortisol and higher pogesterone/allopregnanolone. The crashes suggest metabolism is low, since after lowering cortisol the body turns to thyroid for energy and if there is none/little then you crash.
Peat has written about the "drunk" and hangover feelings from progsterone. Allopregnanolone gives people the same feeling. Google both hormones and the Wikipedia page for both describes these effects. So, pregnenolone is actually giving you a pretty good signal in this case - a signal that you are still mostly running on stress hormones and you need to increase thyroid output or lower FFA that may be blocking repiration even in the presence of normal thyroid.
Just my 2c.

Have some doubts about this,

1. High progesterone and low cortisol; couldn't this be a warning for checking if the problem may rely on any of the enzymes implicated in the Progesterone-Cortisol pathway underworking and constipating the conversion? 17a, 21 or 11b-Hydroxylase?

2. When cortisol is deficient, wouldn't be wise to correct this first on the root, rather than force an increase of thyroid in a cortisol insufficiency scenario?

3. Is cortisol a stress hormone, or anti-stress hormone actually?

Yes, on #1 you have a point. But where did you see in the posts discussion about high progesterone and low cortisol situation which would be indicative of enzyme underactivity?
On #2, if the cortisol is indeed low this would suggest adrenal insufficiency known as Addison disease. Very few people have this condition but even they can benefit from some pregnenolone or progesterone. Pregnenolone and progesterone lower increased cortisol production, not physiological levels, and the also can increase low levels of cortisol. The studies posted in this thread all discuss stress-induced increase in cortisol. As the other human study on people with mental conditions showed, pregnenolone has no effect if cortisol is not elevated. So, bottom line is that if cortisol is high or low pregnenolone can correct the deviation, and if cortisol is normal then pregnenolone probably has no visible effect except maybe improved memory.
On #3, cortisol is a stress hormone - it's primary purposes include dissolving muscle tissue for conversion into glucose, suppressing pain/inflammation, and exciting the brain. Short term effects are probably OK, but I am not aware of a single long-term positive effect of cortisol. If you know of one please share.
 
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Agent207

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Sorry I tought you said sugar crashes related to high progesterone low cortisol and I remembered that condition about possible enzymes impairment.

I think its a logical step in the body to slow down metabolism when blood sugar cant be sustained and theres no cortisol enough to manage the situation: low thyroid / metabolism is the consequence of long term the previous scenario.

I see cortisol more as anti-stress hormone, controlling inflammation to cause more damage. Uncontrolled inflammation with no cortisol may be more stressing and destructive especially long-term. Thats why I see it protective; the ideal is trying it wont have to be increased becouse it wont be needed. But we don't always can avoid stressful happenings, and in that case, better to have cortisol to lessen the mess; without it, thyroid and metabolism will slow down much more quicky, don't you think?
 
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Agent207 said:
post 118823 Sorry I tought you said sugar crashes related to high progesterone low cortisol and I remembered that condition about possible enzymes impairment.

I think its a logical step in the body to slow down metabolism when blood sugar cant be sustained and theres no cortisol enough to manage the situation: low thyroid / metabolism is the consequence of long term the previous scenario.

I see cortisol more as anti-stress hormone, controlling inflammation to cause more damage. Uncontrolled inflammation with no cortisol may be more stressing and destructive especially long-term. Thats why I see it protective; the ideal is trying it wont have to be increased becouse it wont be needed. But we don't always can avoid stressful happenings, and in that case, better to have cortisol to lessen the mess; without it, thyroid and metabolism will slow down much more quicky, don't you think?

I think short term elevations of cortisol can be useful but I would not call it anti-stress hormone. DHEA is anti-stress hormones and if the adrenals are working well DHEA is always co-released with cortisol to protect from its damage. As an analogy, short term elevations of estrogen and HIF are necessary for wound healing but if these continue to be elevated for months/years the organism will develop cancer.
 
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natedawggh

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haidut said:
For some reason this has been a recurring topic on the forum and people have been talking about the "pregnenolone steal" as something mentioned by Peat. Peat actually said there is no such thing and ridiculed the idea. More importantly, pregnenolone protects the brain from the damage of cortisol and the main mechanism is by elevation of progesterone and allopregnanolone. If you look at this thread, you will see that 500mg daily dose of pregnenolone elevated both progesterone and allopregnanolone by several fold.
http://www.raypeatforum.com/forum/viewt ... ors#p64315

This study shows that allopregnanolone reduces levels of both ACTH and cortisol in humans.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351805/
"...Further, allopregnanolone attenuates stress-induced increases in adrenocorticotrophic hormone and corticosterone (Patchev et al., 1996). In humans, stress induces increases in progesterone and allopregnanolone (Childs & de Wit, 2009; Droogleever Fortuyn et al., 2004)."


And here is the study on allopregnanolone effects on humans, referenced by above quote:
http://www.ncbi.nlm.nih.gov/pubmed/8946427/

From the study above:
"...Thirty minutes after exposure to intermittent air puffs, plasma ACTH, and serum CORT levels in vehicle treated rats were significantly increased above those measured in nonstressed animals. Single injections of 50 mcg/kg of THP (allopregnanolone) or P4 (progesterone), before emotional stress significantly attenuated the stress-induced increase in ACTH and CORT. Pretreatment with DEX virtually abolished the pituitary-adrenal secretory response to stress (Figure 2)."

"...In summary, this study indicates that the neurosteroid THP (allopregnanolone)) attenuates the endocrine response to stress and affects the gene transcription of AVP in the PVN in a pattern similar to that seen with glucocorticoids and P4 (progesterone). However, unlike CORT and P4, THP failed to influence the transcription of genes encoding corticosteroid receptors in the hippocampus. These results are largely supportive of the hypothesis that certain ring-A-reduced steroid derivatives may act as endogenous suppressors of the stress response (cf., Purdy et al. 1991) and document a dichotomy in the effects of THP upon neural substrates, subserving neuroendocrine and behavioral adaptation. However, because the changes described herein were induced by exogenously administered neurosteroids, further evidence is needed to ascertain that endogenously produced neurosteroids act in a similar fashion under physiological conditions."

I have attached an image from the study showing the decreases in cortisol and ACTH after allopregnanolone administration.



As you can see allopregnanolone lowered both cortisol and ACTY by aboout 60%. Progesterone lowered them even more, so taking pregnenolone which metabolizes into both should have even stronger effect.
Btw, the allopregnanolone dose used was relatively low. Human equivalent dose would be 50mg - 70mg of allopregnanolone. Since pregnenolone metabolizes about 80% into progesterone, and progesterone metabolizes about 70% into allopregnanolone - this means that taking 90mg - 120mg of pregnenolone would give you the desired levels of allopregnanolone to significantly inhibit cortisol and ACTH (the stress response). This is strikingly similar to the pregnenolone dose of 100mg - 150mg that Ray recommends taking daily to control stress. Once again, the man knows his stuff
!!!

I hope we can put that issue to rest, as it seems it is stopping many people from experimenting with pregnenolone, which happens to be one of the most broadly acting tools in Peat-land.

My personal experience would completely agree with this. I take pregnenolone regularly and bein very sensitive to rises in cortisol, have never experienced elevated levels in conjunction with pregnenolone admin. In fact I always experience quite a profound relaxing of tension on taking it. I also visually see increases of muscle tone and size, which would be opposite were cortisol raised.
 

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whats the highest amount of pregnenolone someone can take? I recall RP saying sometimes you might need to start with several 100mg to make a difference. I dont know how much this would be?

Is there such thing as pregnenolone toxicity?
 

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I just read Peat's article on the three youth hormones. He specifically mentions cortisone the inactive molecule. He does not mention cortisol?? Am I missing something here.
 
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I just read Peat's article on the three youth hormones. He specifically mentions cortisone the inactive molecule. He does not mention cortisol?? Am I missing something here.

Hydrocortisone is cortisol. Sometimes he uses cortisone and hydrocortisone interchangeably, which can be confusing.
 

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Hydrocortisone is cortisol. Sometimes he uses cortisone and hydrocortisone interchangeably, which can be confusing.

So confusing, especially trying to get my head around 11β-HSD2 & 11β-HSD1 interconversion from inactive to active in the different organs and tissue sites and implications in disease conditions. Still, why would he confuse them? He would not confuse T4 with T3 and use them interchangeably or confuse T3 with RT3??

Sorry if I am being too anal.
 
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So confusing, especially trying to get my head around 11β-HSD2 & 11β-HSD1 interconversion from inactive to active in the different organs and tissue sites and implications in disease conditions. Still, why would he confuse them? He would not confuse T4 with T3 and use them interchangeably or confuse T3 with RT3??

Sorry if I am being too anal.

He is not confusing them. Some doctors often call hydrocortisone (cortisol) just cortisone. It is standard practice. The real cortisone which is being produced by 11b-HSD2 deactivating hydrocortisone (cortisol) is rarely talked about and is then called 11-dehydrocortisone to distinguish it.
 

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He is not confusing them. Some doctors often call hydrocortisone (cortisol) just cortisone. It is standard practice.

OK, they can be forgiven for confusing the two; they need to stop doing this and it can no longer be standard practice. What we are only starting to understand is a dysregulation of the ratio of cortisone/cortisol has implications in certain disease conditions. Understanding the relationship between the two will help to make sense why individuals on this forum are experiencing differing reactions to pregnenolone. Some have experienced positive reactions while others experience negative reactions. I for one have experienced both positive and negative. So there is still much we need to learn. There is never been a better time to learn than the present. I think our knowledge will grow exponentially now that we have the right tools and understanding.
 

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Re: Pregnenolone does NOT increase cortisol



Oh, yes! If it does not give you insomnia for whatever reason (<5% of people experience that) pregnenolone before bed would be perfect to lower cortisol and keep the body in an anabolic state and recover brain, tissues, etc.

What's the dose you like for this purpose?
 
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What's the dose you like for this purpose?

No more than 10mg at a time. Human studies showed even 1mg before bed had robust sleep promoting effect.
 

Ella

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I didn't have facial hair before oral Pregnenolone.
Dosing history: I had tried 50mg in the morning and 50mg evening for a while and the facial hair started. I went off it and things seemed better. I went back on at 50mg/day and the problem came back. :(

I experienced the same. I was doing 100mg in the beginning 2 - 3 times a week and felt great but notice hair on my lip growing longer, then chin hairs. I reduced dose to 25mg. I applied progesterone to the area and it did nothing. Now I have gone off pregnenolone and notice the hairs become much finer.

Have you managed to find a solution besides using an epilator?

My face also got large with big fat cheeks. People would comment that I was looking healthy, however, I did not find it flattering at all. What they really meant was that I had a fat face. My face was never fat. I had my driver's license renewed and my photo looked nothing like I used to look. I hate the look and can't bare to see myself in photos. I like seeing the definition of my cheek bones. My face got fat during pregnancy but it was that healthy pregnancy look; this was different.

I stopped the pregnenolone and my face is looking more like my old self. I build muscle very quickly and I think this is due to high androgens.
 

kayumochi

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Re: Pregnenolone does NOT increase cortisol



The US is one of the cheapest for private blood testing.

Just recently I heard of a company called Theranos that offers blood testing for pennies: full thyroid panel for $50 with other basic tests under $10.

Feel free to skim through Peata's post history. You'll have to revise what you call 'dickish'.


I know the above post is from 2015 but the mention of Theranos ... well, so laf
 

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This could definitely explain why I have felt so tired lately and my joints have been so sore. When I combine pregnenlone, aspirin, dhea, vitamin k, 5a-dhp, niacinmide, coffee, gelatin, and a peaty diet I would expect to see fantastic results but actually I begin to feel tired and irritable.
 

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