Pregnenolone causes adrenal suppression?

Joined
Mar 10, 2021
Messages
21,494
Was orally only, then suppositories now (home made, about 80mg, with also high doses melatonin : 400mg eod)
Wow people on this forum get so creative! How is that more beneficial? Is the pregnenalone put on a tampon or??
 

Yucca

Member
Joined
Jan 26, 2021
Messages
226
Location
France
I don’t understand…put on a tampon ?

I make my own suppositories, with witepsol (special wax for this use), melatonin powder and preg powder. Every 3g suppository contains 500mg reduced glutathione, 150mg pregnenolone and about 350-400mg melatonin. I take one eod.
 
Joined
Mar 10, 2021
Messages
21,494
I don’t understand…put on a tampon ?

I make my own suppositories, with witepsol (special wax for this use), melatonin powder and preg powder. Every 3g suppository contains 500mg reduced glutathione, 150mg pregnenolone and about 350-400mg melatonin. I take one eod.
Ohhhh! Forgive my ignorance cause I had no clue how one goes about that. I know a lot about a lot, but I don't know about a whole lot of things. I am gonna have to look that up so I can envision it. Thank you again Yucca for taking the time to educate me on these things.
 

metamorph

Member
Joined
Dec 26, 2021
Messages
136
Location
California
The use of exogenous glucocorticoids such as Hydrocortisone over a long period of time can lead to adrenal suppression. Hydrocortisone inhibits the release of CRH from the hypothalamus, thus inhibiting the release of ACTH from the anterior pituitary gland. Over time, this leads to atrophy of the corticotrophin cells in the anterior pituitary gland, causing the suppressed synthesis of ACTH, and thus glucocorticoid release from the adrenal cortex.
Exogenous pregnenolone inhibits the release of CRH from the hypothalamus, thus inhibiting the release of ACTH from the anterior pituitary gland.
So does pregnenolone causes adrenal suppression? @haidut

The reason I ask is because after using topical pregnenolone for months, I now am completely debilitated with severe symptoms indicative of adrenal insufficiency.
I asked Ray about this because I severely suppressed my HPA-Axis due to long term topical steroid usage. I saw your post and wanted to make sure. Here's his concise response:

"There’s no way that it could cause adrenal suppression. I think someone has misinterpreted the observation that a large amount of it can reduce abnormally high cortisol, normalizing it." - Ray Peat
 

haidut

Member
Forum Supporter
Joined
Mar 18, 2013
Messages
19,798
Location
USA / Europe
The use of exogenous glucocorticoids such as Hydrocortisone over a long period of time can lead to adrenal suppression. Hydrocortisone inhibits the release of CRH from the hypothalamus, thus inhibiting the release of ACTH from the anterior pituitary gland. Over time, this leads to atrophy of the corticotrophin cells in the anterior pituitary gland, causing the suppressed synthesis of ACTH, and thus glucocorticoid release from the adrenal cortex.
Exogenous pregnenolone inhibits the release of CRH from the hypothalamus, thus inhibiting the release of ACTH from the anterior pituitary gland.
So does pregnenolone causes adrenal suppression? @haidut

The reason I ask is because after using topical pregnenolone for months, I now am completely debilitated with severe symptoms indicative of adrenal insufficiency.

I agree with Ray's comment that it cannot cause the adrenal suppression that glucocorticoids cause. The latter cause the suppression by binding to and activating the glucocorticoid receptor (GR) - i.e. they act as agonists on it, and this triggers negative feedback through CRH->ACTH. In contrast, pregnenolone (P5) does not have such an effect on GR and in fact acts as a type of "silent antagonist" - i.e. prevents the translocation of the GR into the cell nucleus needed for glucocorticoids to exert their effects. So, the overall effects of P5 are similar to a GR antagonist but without directly binding to the GR receptor. The drop in 17-keto steroids seen in people using P5 is likely due to elevated P5 being recognized by the adrenals as a form of increased "reserves" so they reduce their own output accordingly. However, that 17-keto steroid drop as a result of P5 supplement is simply a return to baseline (unstressed) state. It has never been shown to reach zero, which is what real adrenal suppression by glucocorticoids does. The human studies with even 500mg P5 daily did not find suppressed cortisol. See below.

@metamorph
 
Last edited:

metamorph

Member
Joined
Dec 26, 2021
Messages
136
Location
California
I agree with Ray's comment that it cannot cause the adrenal suppression that glucocorticoids cause. The latter cause the suppression by binding to and activating the glucocorticoid receptor (GR) - i.e. they act as agonists on it, and this triggers negative feedback through CRH->ACTH. In contrast, pregnenolone (P5) does not have such an effect on GR and in fact acts as a type of "silent antagonist" - i.e. prevents the translocation of the GR into the cell nucleus needed for glucocorticoids to exert their effects. So, the overall effects of P5 are similar to a GR antagonist but without directly binding to the GR receptor. The drop in 17-keto steroids seen in people using P5 is likely due to elevated P5 being recognized by the adrenals as a form of increased "reserves" so they reduce their own output accordingly. However, that 17-keto steroid drop as a result of P5 supplement is simply a return to baseline (unstressed) state. It has never been shown to reach zero, which is what real adrenal suppression by glucocorticoids does. The human studies with even 500mg P5 daily did not find suppressed cortisol. See below.

@metamorph
Question: I am currently in topical steroid withdrawal after 30yrs of usage. The last 7yrs before I began my withdrawal I was using clobetasol which is 600x more potent than hydrocortisone. I used it over the whole body off & on for 7yrs as advised by the derm. When I quite topicals cold turkey 18mos ago I went into severe withdrawal. I'm getting better slowly but surely but it has definitely been a torturous journey. Because of HPA-Axis suppression I presume my cortisol is minimal and/or very imbalanced. What would be a good remedy here and to better navigate TSW? Thanks.
 

Similar threads

M
Replies
0
Views
1K
member 6316
M
Back
Top Bottom