preg_brain

Pregnenolone – The Master Hormone

In Neurosteroids by Tyler S4 Comments

Pregnenolone, the ultimate precursor steroid and neurosteroid.  I’ll admit out of all the hormones, pregnenolone was always not one of my favorites (until recently) due to the fear of it being converted into estrogen and cortisol, but studies actually show the opposite, which I will get into later.

I was always a “visual” learner so I like to start off with a pretty picture- way easier to understand.

Pregnenolone

Preg was discovered back in the 1930’s, for both its anti-inflammatory and anti stress properties.  It was actually pretty popular when it was first discovered with experiments ranging from anyone from factory workers and airplane pilots.  It truly is an interesting compound, but lost its spotlight when the new start hit the block called hydrocortisone (cortisol) in 1955.  Hydrocortisone got a lot of fame due to the fact that it can treat rheumatoid arthritis, which preg was also being investigated for at the time with doses in the 500mg range.  The issue with hydrocortisone is that the anti-inflammatory properties come from its immune suppression (similar to fish oil’s anti-inflammatory “effect”).

Also, cortisol can cause all other host of negative issues like weight gain, muscle loss (due to the catabolic activity), brittle bones, excess fat deposits etc.

You get it, cortisol is bad, but your body still requires some for optimal function.

Back to pregnenolone, well it turns out that preg actually stimulates metabolism (thyroid conversion), LOWERS cortisol, and can LOWER estrogen.  Weird right?  Well, that is what I originally thought before I started supplementing and looking at the studies myself, but let’s take a look at the paperwork.

Anti-cortisol mechanism of preg [here], [here], and [here].  If you look at second and third study, the mechanism is through our favorite neurosteroid friend, Allopregnanolone.

“These results show that (i) pregnenolone has neuroprotective effects against both glutamate and amyloid beta protein neuropathology and (ii) prevention of glucocorticoid receptor (GR) localization to the nucleus may be involved in the observed neuroprotective effects of pregnenolone against glutamate neurotoxicity.”

“Further, allopregnanolone attenuates stress-induced increases in adrenocorticotrophic hormone and corticosterone

“These results demonstrate that the neurosteroid THP and its precursor P4 resemble glucocorticoids in their suppression of the pituitary-adrenal response to emotional stress; however, THP influences the transcription of glucocorticoid-responsive genes in brain structures involved in the regulation of the hypothalamo-pituitary-adrenal system in a fashion that is quite distinct from that obtained with glucocorticoids.”

Pregnenolone

Let’s take a look at preg’s estrogen lowering capabilities [here].  It looks like it lowers estrogen by inhibiting aromatase, which basically means it preg can’t be used as raw material to create more estrogen.

“This inhibitory action, of the mixed non-competitive type, is characterized by a decrease in the apparent Vmax and an increase in the Km value, suggestive of an androgen inhibition of FSH-stimulated aromatase synthesis. This inhibition was also shown by the other 5 alpha- and 5 beta-reduced androgens: 5 beta-androstanedione was the most effective, while DHT was the least. Other steroids such as pregnenolone and progesterone were inhibitory, but testosterone and diethylstilboestrol were stimulatory. These results suggest an important mechanism for the intrafollicular control of oestrogen synthesis, involving a possible reciprocal relationship between aromatase and 5 alpha-reductase activities.”

Prgenenolone’s Neuroprotective Functions

The other area I really wanted to highlight is preg’s strong neuroprotective properties.  Many of the benefits don’t only from just pregnenolone, but its neurosteroid metabolites which are pregnenolone sulfate, allopregnanolone, and DHEAS.  The first two listed are GABAergenic, which at the end of the day means “anti stress”.  So it’s a no brainer why preg can help with so many neurodegenerative diseases [here] [here] [here].

Significant improvement was observed in weeks 6 and 8 of pregnenolone therapy among patients who were not treated with concomitant mood stabilizers (arms × visit × mood stabilizers; P = 0.010). Likewise, pregnenolone significantly reduced Assessment of Negative Symptoms scores compared to placebo (d = 0.57), especially on blunted affect, avolition and anhedonia domain scores. Other symptoms, functioning, and side-effects were not significantly affected by adjunctive pregnenolone. Antipsychotic agents, benzodiazepines and sex did not associate with pregnenolone augmentation. Pregnenolone was well tolerated.

Thus, add-on pregnenolone reduces the severity of negative symptoms in recent-onset schizophrenia and schizoaffective disorder, especially among patients who are not treated with concomitant mood stabilizers. Further studies are warranted.”

Finally, from my personal standpoint, I was always skeptical about giving pregnenolone a shot due to fear of the conversion to estrogen and cortisol.  After further research and self experimentation, I think it is by far one of the most important steroid neurosteroids in the human body.  It can especially beneficial to anyone who has a high stress job or someone who has some sort of hormonal issue whether it’s from the use of AAS or finasteride.  From direct supplementation, your body will convert the proper hormones to where it’s needed and at the same time stimulating your endogenous (natural) pregnenolone synthesis which basically means it’s not going “shut you down” when supplementation ceases.  The proper term is called positive feedback loop compared to negative feedback loop which is what happens when one supplements with anabolic steroids.
Just to give you another example of this would be DHT, another protective steroid that was shown to have a positive feedback mechanism [here].
“Furthermore, the restoration of prostate growth after castration and the enhancement in 5 alpha-reductase enzyme activity and 5 alpha-reductase messenger RNA level by testosterone administration were blocked by finasteride, whereas the inhibitor had no effect on dihydrotestosterone-mediated increases in 5 alpha-reductase activity or messenger RNA level. These findings indicate that dihydrotestosterone itself controls prostate growth and 5 alpha-reductase activity. They further suggest that prostate growth is controlled by a feed-forward mechanism by which formation of trace amounts of dihydrotestosterone induces 5 alpha-reductase, thereby increasing dihydrotestosterone synthesis and triggering a positive developmental cascade.””

Pregnenolone’s Relationship in Regards to Restoring the HPTA 

I thought these studies were in particular interesting especially if you are a bodybuilder or occasionally use AAS, exogenous hormones, prohormones etc.
So chronic administration of AAS in bodybuilders actually depletes allopreg levels in the brain which is probably responsible for the anxiety and irritability reported by users of AAS [here].  It would be even worse if the AAS had estrogenic properties (dianabol for example) as well since estrogen itself is known to cause irritability and anxiety especially in the form of an emotional manner [here] [here].
Supplementing pregnenolone along with AAS or even in PCT could have the following benefits:
  • it helps raise allopregnanolone
  • it seems to protect the gonads from atrophy induced by AAS and pituitary suppression. In castrated animals, pregnenolone is capable of maintaining completely normal fertility and tissue androgen levels even though serum androgen levels are undetectable.
Back in the 1940s pregnenolone was used to cure infertility in men by restoring normal sperm production just like during PCT (post cycle therapy)[here] [here] [here].
A common over the counter non-toxic version of a “PCT”, could be something like ~100-150mg of pregnenolone either alone or combined with 5mg of DHEA taken daily.
To wrap up, if you want to try experimenting with pregnenolone supplementation, I found a few solid vendors.
Dosage wise, lower amounts will be more anabolic/androgenic (<50mg) and higher amounts (>50mg) will provide more neurosteroid type properties due to the higher conversion of allopregnanolone and progesterone which was noted in my previous post focusing on allopreg here.
Possible vendor choices:
  • For pure (tested) and clean (no fillers) preg powder- check out here.
  • For pure (tested) and clean (no fillers) preg liquid (“StressNon” or “Pansterone”)- check out here.

I have no affiliation with either vendor listed, but have tried each of them in the past with both solid results.  I can however, vouch personally for the second option listed (Idealabs), the owner (Haidut) is a researcher himself and definitely knows his products in terms of the research behind them.

Comments

  1. Luis

    Great job, I think finally ex finasteride users can understand better what could be going on, and maybe this information hep us to recover from baseline and beyond!

  2. John

    Hey Marcel, frequent reader here. Your research is sound and extremely informative. I would like to understand the reason(s) behind your research and the smarts that are able to see such good research.

    1. Marcel

      Thank you John. This post was written by Tyler though. He has a bunch more coming.

      Reason behind my research is interest, business, and jacking up hormones so I feel phenomenal at most times.

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