Optimal Dose Of Pregnenolone For Androgen Synthesis

[haidut]

OMG. Really ? I never thought about using pregnenolone intranasally.

@haidut do you think is there any big risk on snorting a line of pregnenolone powder ? I'm 100% serious. I have some Healthnatura pure preg powder here and I'm willing to use it myself as a resus monkey for the sake of science... Do you think it's dangerous ? After all, the olfactory bulb is part of the brain, so anything going there would bypass the BBB protective mechanisms, if I'm not wrong.

Well, that approach has been tried before in humans so it should work. I am just not sure of the proper dose and what side effects it can cause. I know some people experience nose bleeds from oral pregnenolone so something to watch out for. Also, given that the i.v. route was better than intranasal based on the study, applying a bit of StressNon along a bigger vein of your arm should achieve the same. Just pick one of the visible veins under the skin, or even better would be a bulging vein of length at least 2in. Apply the SressNon on it and voilla, you have a decent surrogate for IV administration without the risks of snorting stuff And the snorting can get you arrested, at least in the US, even if you snort legal stuff.

 

[Makrosky]

Well, that approach has been tried before in humans so it should work. I am just not sure of the proper dose and what side effects it can cause. I know some people experience nose bleeds from oral pregnenolone so something to watch out for. Also, given that the i.v. route was better than intranasal based on the study, applying a bit of StressNon along a bigger vein of your arm should achieve the same. Just pick one of the visible veins under the skin, or even better would be a bulging vein of length at least 2in. Apply the SressNon on it and voilla, you have a decent surrogate for IV administration without the risks of snorting stuff :) And the snorting can get you arrested, at least in the US, even if you snort legal stuff.

Thanks haidut!! I'm not in the US. I would try both and let you know if I feel something different than oral/topical route.

@Regina don't react like that... It's for science

 

[Regina]

Thanks haidut!! I'm not in the US. I would try both and let you know if I feel something different than oral/topical route.

@Regina don't react like that... It's for science :)

 

[DaveFoster]

@haidut

After dropping my pregnenolone dosage from 100-150 mg to just 30 mg (3 mg topical applied w/ DMSO to the testes), I've noticed significant more androgenecity than the larger dose.

I didn't even read your post in the middle of this thread with the 30-50 mg recommendation, and that's just personal experience, so it matches up!

I've also added progesterone, which seems to have a very potent androgenic effect at low doses, as you've mentioned.

Maybe next an "Optimal Dose of Progesterone for Estrogen Without Androgen Antagonism."

 

[haidut]

@haidut

After dropping my pregnenolone dosage from 100-150 mg to just 30 mg (3 mg topical applied w/ DMSO to the testes), I've noticed significant more androgenecity than the larger dose.

I didn't even read your post in the middle of this thread with the 30-50 mg recommendation, and that's just personal experience, so it matches up!

I've also added progesterone, which seems to have a very potent androgenic effect at low doses, as you've mentioned.

Maybe next an "Optimal Dose of Progesterone for Estrogen Without Androgen Antagonism."

That's great feedback and great idea too! Let me see what I can dig up on progesterone supplementation and its effects on androgens and I will make a separate post.

 

[milk_lover]

I think taking 10mg pregnenolone 5-10 times daily orally will have very different effect than taking 50mg - 100mg in a single setting. It would be more balanced in smaller, frequent doses as it would go down both the progesterone and DHEA pathyways. In higher single doses it would be mostly a progesterone and allopregnanolone effect, so not very androgenic for males but maybe perfect for females. Topical pregnenolone (dissolved in DMSO) will to gown along 3 pathways - the 5-AR route (5a-DHP, allopregnanolone), the 3b-HSD route (DHEA) route, and remaining as unchanged pregnenolone. Exactly what percentage of the pregnenolone will go down each route is unknown, but it is known that topical pregnenolone feels more androgenic than oral (at the same dose) and seems to stimulate conversion of DHEA down the androgen pathways and away from estrogen. The scrotal application of pregnenolone/dhea/K is probably the best way for males to raise serum androgens and have most of pregnenolone and DHEA go down the androgen pathway. Oral pregnenolone will give more of a progesterone response, and topical (but not on scrotum) will give some androgenic, some progesterone and some unchanged pregnenolnoe response. Since the optimal way for everybody is different, I suggest experimenting with different doses and routes and sticking with the one that makes you feel best.

As I explained in my response to Wagner above, the fate of pregnenolone metabolism depends on the route of delivery and the dose and nobody knows for sure how exactly it pans out. The information we do have is that if you want pregnenolone to have a more balance effect and convert down both the progesterone and DHEA pathways then using smaller doses more frequently would be better than taking the same total dose once. So, taking 10mg doses 5 times a day for a total of 50mg will have a more balanced effect than a single dose of 50mg. This is hinted to by some of the human studies, which found benefit from lower doses pregnenolone for specific conditions but not form the higher dose. The dose that was found to work was 30mg - 50mg daily. Higher doses may also work, but the higher the dose the more it is going to favor the progesterone pathway with all of its benefits and side effects. If depression in men is mostly driven by androgen deficiency (which is what happens in hypothyroidism) then smaller doses more regularly would be better. Higher dose pregnenolone, is probably very effective as an anti-cancer strategy and the studies I have seen (mostly in vitro) show that it is the most potent inhibitor of liver, kidney, and skin cancer available, and that effect is dose-dependent. So, you'd need 400mg+ pregnenolone in a single dose to see effects against liver cancer and melanoma, but lower doses are more for optimizing steroid pathways. Thus, it seems the lower doses would be optimizing hormone balance and preventing bad stuff from happening, while the higher doses would be for situations where crap has already hit the fan and males do not care about the progesterone dominance high dose pregnenolone may lead to. See below studies for lower vs. higher dose pregnenolone - i.e. the best effect was reported with doses of 30mg and 50gm daily, 200mg daily was ineffective, and positive effects again begin to emerge beyond 500mg daily.
Pregnenolone and dehydroepiandrosterone as an adjunctive treatment in schizophrenia and schizoaffective disorder: an 8-week, double-blind, randomiz... - PubMed - NCBI
"...RESULTS: Compared with subjects who received placebo, those administered PREG-30 had significant reductions in positive symptom scores and extrapyramidal side effects (EPS) and improvement in attention and working memory performance, whereas subjects treated with PREG-200 did not differ on outcome variable scores for the study period. The general psychopathology severity and general functioning of patients receiving placebo and PREG-30 improved more than that of those subjects treated with DHEA, while EPS improved more in subjects treated with DHEA than in patients receiving placebo. Negative symptoms and akathisia were not significantly benefited by any treatment. The administration of PREG and DHEA was well tolerated."

Adjunctive pregnenolone ameliorates the cognitive deficits in recent-onset schizophrenia. - PubMed - NCBI
Add-on Pregnenolone with L-Theanine to Antipsychotic Therapy Relieves Negative and Anxiety Symptoms of Schizophrenia: An 8-week, randomized, double... - PubMed - NCBI
Pregnenolone treatment reduces severity of negative symptoms in recent-onset schizophrenia: an 8-week, double-blind, randomized add-on two-center t... - PubMed - NCBI
Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia. - PubMed - NCBI

Wow haidut very extremely helpful and thorough answers to my questions/concerns about pregnenolone. Can't thank you enough :) :)

Does anybody know the Brazilian man on the forum who was asking about pregnenolone a lot? He previously had his daughter/granddaughter with him as a profile picture. I am pretty sure those responses from haidut would help him immensely. @Blossom can you link his name here if you know who I am talking? Thanks

 

[Blossom]

Wow haidut very extremely helpful and thorough answers to my questions/concerns about pregnenolone. Can't thank you enough :) :)

Does anybody know the Brazilian man on the forum who was asking about pregnenolone a lot? He previously had his daughter/granddaughter with him as a profile picture. I am pretty sure those responses from haidut would help him immensely. @Blossom can you link his name here if you know who I am talking? Thanks

Sure, I believe you are thinking of @bzmazu.
ETA Although I just checked and he lives in Belize.

 

[milk_lover]

Sure, I believe you are thinking of @bzmazu.

yeah thanks him and @gilson dantas could benefit from those answers :)

 

[Blossom]

yeah thanks him and @gilson dantas could benefit from those answers :)

I was just thinking the same thing!

 

[InterrogaOmnia]

@haidut

After dropping my pregnenolone dosage from 100-150 mg to just 30 mg (3 mg topical applied w/ DMSO to the testes), I've noticed significant more androgenecity than the larger dose.

I didn't even read your post in the middle of this thread with the 30-50 mg recommendation, and that's just personal experience, so it matches up!

I've also added progesterone, which seems to have a very potent androgenic effect at low doses, as you've mentioned.

Maybe next an "Optimal Dose of Progesterone for Estrogen Without Androgen Antagonism."

Are you still using pansterone?

 

[DaveFoster]

Are you still using pansterone?

Yes; I apply 2 drops on my balls three times per day for a total of 6 drops (3 mg DHEA and 3 mg pregnenolone).

 

[haidut]

I just wanted to post this link for those interesting in reading more about the biphasic effects of pregnenolone. So, @DaveFoster and @Makrosky - check this link out. It basically expands on the discussion we had in this thread.
Epiphany: Why Low Doses can work differently, or “Biphasic, U-shaped actions at the GABAa receptor”

 

[DaveFoster]

@haidut

Absolutely; thanks for the link. I just tried 0.65 progesterone (Progestene) in DMSO applied to the testes, as I got my usual mid-afternoon anxiety, and the anxiety went away, as did any sexual angst (urge to engage in sex).

I e-mailed Ray, and he said he thought the DMSO was responsible for the effect, as the dosage of progesterone is too low, but I haven't experienced the same with just a drop of DMSO, so it's probably the progesterone.

 

[Wagner83]

Did you send the study of dmso potentiating steroids effects to Ray?

 

[Makrosky]

I just wanted to post this link for those interesting in reading more about the biphasic effects of pregnenolone. So, @DaveFoster and @Makrosky - check this link out. It basically expands on the discussion we had in this thread.
Epiphany: Why Low Doses can work differently, or “Biphasic, U-shaped actions at the GABAa receptor”

Wow! Thanks haidut!!!!

The thing is ... yes, a certain dose of pregnenolone can generate an allopregnenolone ammount that falls in the middle of the U shape, thus being counterproductive. BUT... PREG will convert also to other androgens and progesterone and stop there, right? The androgens and progesterone some of them have sedative/anaesthesic effects (I don't know if it's via the GABA system) so it ends up balanced? That might explain why some people no matter the dose of pregnenolone they take, they don't experience any U shape like reactions. I'm hypothesizing haidut, don't know really.

But yes, definitely, something to keep in mind.

It's not like 5a-DHP which can only be converted to Allopreg. With 5a-DHP it would be much easier to see how this U shape works I guess.

I for sure experiment diverse reactions, depending on the dose, which I never happen to think to in terms of a U-shaped action of allopreg in the GABAa receptor. I'll keep it in mind from now and see if it correlates well.

 

[Makrosky]

@haidut

After dropping my pregnenolone dosage from 100-150 mg to just 30 mg (3 mg topical applied w/ DMSO to the testes), I've noticed significant more androgenecity than the larger dose.

Hey Dave,

So you are assuming DMSO potentiation of 10x ?

 

[haidut]

Wow! Thanks haidut!!!!

The thing is ... yes, a certain dose of pregnenolone can generate an allopregnenolone ammount that falls in the middle of the U shape, thus being counterproductive. BUT... PREG will convert also to other androgens and progesterone and stop there, right? The androgens and progesterone some of them have sedative/anaesthesic effects (I don't know if it's via the GABA system) so it ends up balanced? That might explain why some people no matter the dose of pregnenolone they take, they don't experience any U shape like reactions. I'm hypothesizing haidut, don't know really.

But yes, definitely, something to keep in mind.

It's not like 5a-DHP which can only be converted to Allopreg. With 5a-DHP it would be much easier to see how this U shape works I guess.

I for sure experiment diverse reactions, depending on the dose, which I never happen to think to in terms of a U-shaped action of allopreg in the GABAa receptor. I'll keep it in mind from now and see if it correlates well.

My experiences and the ones of a few other people (I often experiment with as a group) seem to fit the U shaped curve rather well. Pregnenolone in doses of 30mg - 50mg daily is about as androgenic as it is progestogenic. Taking 100mg for a few days is more or less the same but if you keep it for a week it starts to build up enough progesterone to skew things towards progesterone. Anything over 100mg (200mg+ daily) heavily favors the progesterone and allopregnanolone route. Now, the allopregnanolone is a precursor to DHT/androsterone, but the progesterone synthesis seems to dominate so the overall effect of higher dose pregnenolone is very similar to taking pure progesterone.
Of course, everybody is different. Given the propensity of pregnenolone to convert into whatever is deficient in that person, I can see it having androgenic effects even in higher doses if that person is really lacking androgens. The animal studies show that pregnenolone favors the androgen route when the male animals are castrated, and helps maintain normal fertility even in the absence of gonads. In non-castrated male animals it does not have this effect. So, again, pregnenolone helps balance the system by correcting deficiencies. But I think it is easier to balance the system with lower dose over longer period since it does not saturate the enzymes and thus potentially trigger negative feedback systems. Up to 50mg pregnenolone daily is considered a physiological dose and should not skew things too much.

 

[Makrosky]

@haidut

Is it worth posting the biphasic actions blog you mentioned in the 5a-DHP ? I can do that.

It's kind of...leaving a track of bread crumbles in case anyone experiences weird results.

 

[Makrosky]

My experiences and the ones of a few other people (I often experiment with as a group) seem to fit the U shaped curve rather well. Pregnenolone in doses of 30mg - 50mg daily is about as androgenic as it is progestogenic. Taking 100mg for a few days is more or less the same but if you keep it for a week it starts to build up enough progesterone to skew things towards progesterone. Anything over 100mg (200mg+ daily) heavily favors the progesterone and allopregnanolone route. Now, the allopregnanolone is a precursor to DHT/androsterone, but the progesterone synthesis seems to dominate so the overall effect of higher dose pregnenolone is very similar to taking pure progesterone.
Of course, everybody is different. Given the propensity of pregnenolone to convert into whatever is deficient in that person, I can see it having androgenic effects even in higher doses if that person is really lacking androgens. The animal studies show that pregnenolone favors the androgen route when the male animals are castrated, and helps maintain normal fertility even in the absence of gonads. In non-castrated male animals it does not have this effect. So, again, pregnenolone helps balance the system by correcting deficiencies. But I think it is easier to balance the system with lower dose over longer period since it does not saturate the enzymes and thus potentially trigger negative feedback systems. Up to 50mg pregnenolone daily is considered a physiological dose and should not skew things too much.

Cool! Thanks.

 

[DaveFoster]

Hey Dave,

So you are assuming DMSO potentiation of 10x ?

Yeah, for simplicity; also, if it's applied to the testes it will be more potent, hence the multiplier of ten.