Optimal Dose Of Pregnenolone For Androgen Synthesis

[Momado965]

How much stressnon can be daily for optimal androgen synthesis and non of the anti androgenic effects?

 

[Dave Clark]

Haha, I know what you mean. I have a scale that can measure to the 100ths (.01g), but now I could use one that will measure to the 1000ths (.001g), for small powder doses.

Can't the preg powder be mixed with a base powder, say inositol, and then calculated so that a larger dose, i.e. 1/8 or 1/4 teaspoon would yield a small dose of pregnenolone?
I forget exactly how you do that, but I have done it in the past when a powder calls for a dose that is almost impossible to measure. Does anyone remember how to do that? It has been so long ago that I don't recall the procedure.

 

[Mossy]

Can't the preg powder be mixed with a base powder, say inositol, and then calculated so that a larger dose, i.e. 1/8 or 1/4 teaspoon would yield a small dose of pregnenolone?
I forget exactly how you do that, but I have done it in the past when a powder calls for a dose that is almost impossible to measure. Does anyone remember how to do that? It has been so long ago that I don't recall the procedure.

That makes sense. I have done something similar to that, with powders, where I have a large enough measure of one supplement, and then add my smaller dosed supplement that would not register on the scale otherwise. I have the Ideal Labs liquid preg, so what I did was use coconut oil for the larger base (tsp or tbsp), which easily registers on the scale, then add my drop of preg and measure off a tenth(or whatever it was) of the total solution to get my minute dosages.

 

[Momado965]

That dose it probably not going to raise progesterone to the point of causing anti-androgenic effects. The physiological doses of pregnenolone are about 30mg - 50mg daily, so that's pretty much what you are taking with that single weekly dose.

If I took 30mg of stressnon( newest formule ethanol and pyrolidone) which is about 18 drops, will it be anti androgenic? If not, then how many drops of stressnon is possibly anti androgenic?

 

[haidut]

If I took 30mg of stressnon( newest formule ethanol and pyrolidone) which is about 18 drops, will it be anti androgenic? If not, then how many drops of stressnon is possibly anti androgenic?

I don't think it would be anti-androgenic but monitor your symptoms and if things like decreased penis sensitivity or low libido happen then I would decrease the dosage.

 

[Momado965]

I don't think it would be anti-androgenic but monitor your symptoms and if things like decreased penis sensitivity or low libido happen then I would decrease the dosage.

Alright. Cool.

 

[ddjd]

The only one I've heard of (at least of those that seem to respond to questions) is Peter at Vitaspace who can do bulk orders. I haven't looked into his stuff, but I think @charlie was happy with one of his products. And I think he (or someone else?) was able to get some analysis on the product by placing an order.

dan do you know what the minimum order quantity of peters pregnenolone is?

 

[Dan W]

dan do you know what the minimum order quantity of peters pregnenolone is?

I think it's 100g on the pregnenolone. Although maybe he'd offer some kind of sample size if you contacted him?

 

[gilson d dantas]

I was just thinking the same thing!

Thank you Blossom!!!

 

[Mauritio]

Does the body have a pregnenolone store ?
Because people say over time you can reduce the dose you take, is that just because of pregenolones half life ,meaning preg piling up in the blood stream ?

 

[Dave Clark]

Haha, I know what you mean. I have a scale that can measure to the 100ths (.01g), but now I could use one that will measure to the 1000ths (.001g), for small powder doses.

What about diluting your powder with a neutral base powder like inositol, glycine, etc. When I buy health Natura, the micro-spoon is 70 mg, but dilute 50/50 with inositol, now the micro-spoon is 35 mg, and you can go from there until you get the dose you want in the micro-spoon. No reason to try and get a very low dose of something that is so small you can barely see it, much less measure it.
I know I commented on this before, but just wanted to mention that it is very easy to do the 50/50 blend and go from there, i.e. if you wanted a 18 mg {approx} you would do a one part {one bottle of HN pregnenolone} to two parts {two bottle equivalent} of inositol, etc., or for a 9mg {approx} dose, one part to three parts of inositol, etc.
This came to mind since I took notice Nootropicss Depot was selling a 5 mg dose for a hefty price, when it could be had for much cheaper this way.

 

[Mossy]

What about diluting your powder with a neutral base powder like inositol, glycine, etc. When I buy health Natura, the micro-spoon is 70 mg, but dilute 50/50 with inositol, now the micro-spoon is 35 mg, and you can go from there until you get the dose you want in the micro-spoon. No reason to try and get a very low dose of something that is so small you can barely see it, much less measure it.
I know I commented on this before, but just wanted to mention that it is very easy to do the 50/50 blend and go from there, i.e. if you wanted a 18 mg {approx} you would do a one part {one bottle of HN pregnenolone} to two parts {two bottle equivalent} of inositol, etc., or for a 9mg {approx} dose, one part to three parts of inositol, etc.
This came to mind since I took notice Nootropicss Depot was selling a 5 mg dose for a hefty price, when it could be had for much cheaper this way.

That is an interesting idea. By neutral base powder, do you mean something that would have little to no noticeable effect on the body? If so, there is hardly anything I can take, in any amount, that doesn't effect me. With 25mg of taurine or glycine I will feel it negatively, in most cases. Even so, I think I understand what you're saying: dilute the more potent supplement with a more neutral one, in order to micro-dose it and lessen any potential negative effects.

 

[Dave Clark]

That is an interesting idea. By neutral base powder, do you mean something that would have little to no noticeable effect on the body? If so, there is hardly anything I can take, in any amount, that doesn't effect me. With 25mg of taurine or glycine I will feel it negatively, in most cases. Even so, I think I understand what you're saying: dilute the more potent supplement with a more neutral one, in order to micro-dose it and lessen any potential negative effects.

Inositol is not known to have any profound effects until it is taken in gram doses, etc. It has a sweet taste, is a B vitamin that is calming. I like it as a mixing powder since it is usually more powdery than glycine, which has more of a crystalline texture, so it mixes better. But, you could find a powder that you do well with and use that. Magnesium or calcium powder of some sort would work well, too. Whatever you can find that in small quantities in a mix doesn't upset your nutrient dosing in a large way. The small amount of inositol in the mix is only beneficial, and glycine and magnesium or calcium is the same there {something that has a large dosing window, so to speak}. If you look through an A to Z list on PureBulk or Bulk supplements, I am sure you could find an inexpensive powder that you wouldn't mind having a bit more of in your regimen, for mixing. Just make sure the powder has a good consistency, some are very coarse, and some are very powdery and fluffy {that's why I like inositol, it is neither}. Also, I remember Peat saying good things about inositol, so, unless he had changed his mind, it is Peaty.
Prices of glycine and inositol have gone up lately so I may look for an alternative myself at some point. If you do egg shells, you should be good with this: Calcium Carbonate (Mineral) Powder Plus, it is about the cheapest powder on the list.

 

[john_snow]

It has not been tested on too many people but I have tested on myself. Taking the full 20mg dose StressNon topically in one sitting results in about the same pregnenolone concentration as an oral dose of about 200mg pregnenolone. The blood tests were done 1 and 8 hours post administration. Oral StressNon is similar to oral pregnenolone, so no advantage in taking it orally. But topically, StressNon seems to have about 10:1 effectiveness in raising blood pregnenolone levels. Both oral and topical pregnenolone will undergo a heavy conversion into other steroids. Both liver and skin are very active steroidogenic organs. But the liver likes to accumulate pregnenolone (as does the brain) so if you ingest even a hefty dose, very little of it will end up in the bloodstream as unchanged pregnenolone. The liver will convert maybe 60% to other steroids, keep another 30%-35% for itself and only let about 1%-2% unchanged pregnenolone in the blood. Topical pregnenolone , while also undergoing conversion does not metabolize as extensively unless you apply to a really large skin area. So, topical pregnenolone will deliver more unchanged pregnenolone to the blood, especially when the carrier is DMSO.

Hi @haidut, what would be this ratio today with the new formula for pansterone instead of DMSO? Meaning, what dose of pansterone would be about the same as taking 100mg oral pregnenolone today?

 

[Mossy]

Inositol is not known to have any profound effects until it is taken in gram doses, etc. It has a sweet taste, is a B vitamin that is calming. I like it as a mixing powder since it is usually more powdery than glycine, which has more of a crystalline texture, so it mixes better. But, you could find a powder that you do well with and use that. Magnesium or calcium powder of some sort would work well, too. Whatever you can find that in small quantities in a mix doesn't upset your nutrient dosing in a large way. The small amount of inositol in the mix is only beneficial, and glycine and magnesium or calcium is the same there {something that has a large dosing window, so to speak}. If you look through an A to Z list on PureBulk or Bulk supplements, I am sure you could find an inexpensive powder that you wouldn't mind having a bit more of in your regimen, for mixing. Just make sure the powder has a good consistency, some are very coarse, and some are very powdery and fluffy {that's why I like inositol, it is neither}. Also, I remember Peat saying good things about inositol, so, unless he had changed his mind, it is Peaty.
Prices of glycine and inositol have gone up lately so I may look for an alternative myself at some point. If you do egg shells, you should be good with this: Calcium Carbonate (Mineral) Powder Plus, it is about the cheapest powder on the list.

I appreciate the information. I do like your idea of inositol; I've been meaning to try that again. If not that, calcium carbonate is still relatively cheap.

 

[Gorillaquills]

There was a recent discussion about high dose pregnenolone on the forum and some people sent Peat my comments that high dose pregnenolone can inhibit androgen synthesis. Peat replied that he has not seen such effects, but did not directly speak against the idea. Privately, I got quite a few messages accusing me of making stuff up. Well, I was not making stuff up, I was referring to an actual study and also to reports of people who found pregnenolone beyond 200mg daily killed their sex drive. Doses below 100mg had largely stimulating effect on libido and muscle tone, indicative of an androgen boost. The larger doses, as we know from the schizophrenia studies, converted mainly into progesterone and allopregnanolone.
So, here is the study suggesting that there is indeed an optimal range of pregnenolone concentration so that it stimulates the conversion of said pregnenolone down the androgen pathways. Higher than the optimal concentration was suppressive of androgen synthesis from pregnenolone. Unfortunately, the optimal pregnenolone concentrations are different for stimulating androstenedione, DHEA, and 17-OH-pregnenolone synthesis so there is no one size fits all. But I think aiming for not exceeding the optimal concentration that simulated DHEA synthesis (about 2uM) maximally would be a good compromise. Also, as you can see, pregnenolone stimulated synthesis of progesterone in any concentration. So, for androgens synthesis pregnenolone seems to have a bi-phasic effect while for progesterone it is stimulating in any dose. The latter part matches well the human studies with large doses pregnenolone.
While this study concerns mostly oral administration of pregnenolone, application to the scrotum is probably also subject to some restrictions in terms of optimal dose. Some people using the topical approach already noted that higher than 10mg dose of pregnenolone on the scrotum gave them symptoms of progesterone rather than androgen synthesis.
Finally, the study makes the claim that the further away a derivative of pregnenolone is from pregnenolone in the steroid pathways, the more sensitive it is to inhibition of its synthesis by pregnenolone. You can see this effect in the attached image. Lower concentrations of pregnenolone were needed to inhibit androstenedione synthesis than DHEA, since androstenedione is further away from pregnenolone. The next androgen down the line being testosterone, the pregnenolone concentration for its inhibition may be even lower than the one for androstenedione.
TLDR: In lower concentrations pregnenolone increases synthesis of both androgens and progesterone. In higher concentrations, it inhibits androgen synthesis but continues to stimulate progesterone synthesis. If the progesterone synthesis pathway becomes too dominant (as was seen with high dose pregnenolone in humans), that can lead to the anti-androgenic side effects associated with progesterone.

Variation in 3β-hydroxysteroid dehydrogenase activity and in pregnenolone supply rate can paradoxically alter androstenedione synthesis. - PubMed - NCBI
"...Results of the steady-state analysis in which supply of pregnenolone (P5) is varied between 0.01 and 10 uM/s, a sufficiently wide range to capture of all qualitative results, are shown in Fig. 5. Parameters other than P5 supply are the same as in the simulation example in Section 3.2. The curves illustrate that increasing the P5 supply rate initially increases the synthesis of all the steroids; however, when the P5 supply rate reaches a certain level, further increasing this rate will firstly suppress the synthesis of A4, then DHEA, and lastly, 17OHP4. In contrast, increasing P5 supply rate resulted in a continual increase in P4 production."

"...By taking into consideration competitive inhibition of the enzymes by substrates and products, the model shows that when the rate of P5 supply reaches a certain level, further increases in P5 supply rate will suppress the synthesis of A4, DHEA, and 17OH-P4, but not the synthesis of P4. Obviously, at low rates of P5 supply, the concentrations of all steroids are low and inhibition of P450c17 by substrates and 3-HSD by both substrates and products is negligible. Increasing the P5 supply rate progressively increases the synthesis of all the steroids to a point when the steroid concentrations reach levels that are sufficient to start inhibiting the activities ofthe both enzymes. The more reaction steps there are between the precursor substrate P5 and the end product, the stronger the effect of competitive inhibition is on its synthesis. Therefore, as the P5 supply rate increases, the suppression of A4 synthesis occurs first, following by that of DHEA and then 17OH-P4. In turn, this increasingly drives P5 flux down the 4 pathway towards the synthesis of P4. The increased flux down the 4 pathway is able to overcome the effect of the inhibition of 3-HSD by its catalytic substrates and products, allowing P4 synthesis to continue to rise with increasing P5 supply rate."

First off I just wanted to say thanks for all you do.
I have a question, been trying for some time to figure out what the hell is going on with my hormones. Need a little advice.
I just checked my prolactin witch was low @7 ng/dl
But my estodiol was at the top of the scale 42.2 pg/ml. And then did a estrone test as well which came back low @54 pg/ml. The range is huge. 0-174. For being 45, my DHEA is pretty good I think 233ug/dl. But my test is really low. 266 ng/dl. The other problem is that my TSH is really high, in the 7s.
I also checked my cortisol in the morning. Came back 9.2 ug/dl. I don't think that is very high.

I have been using your supplement for some time now.
I'm using pregnenolone/DHEA, progesterone/DHEA. Tyromix and stressnon pregnenolone. Really haven't seen anything change.

I wonder if I need to check my LH hormone?
I just did a pregnenolone, progesterone, dht and a reverse t3 blood test waiting for results.
I have the signature body shape that you discussed in many of your posts. Loves handles , belly fat that just won't go away and difficult time gaining strength. It sucks!!. Love your supplements and all your research content. Thanks man!

 

[Frankdee20]

“have been using your supplement for some time now.
I'm using pregnenolone/DHEA, progesterone/DHEA. Tyromix and stressnon pregnenolone. Really haven't seen anything change.”


Are you saying you tried these to change the mentioned lab findings ?
Or are you saying these supplements you’ve been taking are correlated to the skewed results currently ?

 

[Gorillaquills]

There was a recent discussion about high dose pregnenolone on the forum and some people sent Peat my comments that high dose pregnenolone can inhibit androgen synthesis. Peat replied that he has not seen such effects, but did not directly speak against the idea. Privately, I got quite a few messages accusing me of making stuff up. Well, I was not making stuff up, I was referring to an actual study and also to reports of people who found pregnenolone beyond 200mg daily killed their sex drive. Doses below 100mg had largely stimulating effect on libido and muscle tone, indicative of an androgen boost. The larger doses, as we know from the schizophrenia studies, converted mainly into progesterone and allopregnanolone.
So, here is the study suggesting that there is indeed an optimal range of pregnenolone concentration so that it stimulates the conversion of said pregnenolone down the androgen pathways. Higher than the optimal concentration was suppressive of androgen synthesis from pregnenolone. Unfortunately, the optimal pregnenolone concentrations are different for stimulating androstenedione, DHEA, and 17-OH-pregnenolone synthesis so there is no one size fits all. But I think aiming for not exceeding the optimal concentration that simulated DHEA synthesis (about 2uM) maximally would be a good compromise. Also, as you can see, pregnenolone stimulated synthesis of progesterone in any concentration. So, for androgens synthesis pregnenolone seems to have a bi-phasic effect while for progesterone it is stimulating in any dose. The latter part matches well the human studies with large doses pregnenolone.
While this study concerns mostly oral administration of pregnenolone, application to the scrotum is probably also subject to some restrictions in terms of optimal dose. Some people using the topical approach already noted that higher than 10mg dose of pregnenolone on the scrotum gave them symptoms of progesterone rather than androgen synthesis.
Finally, the study makes the claim that the further away a derivative of pregnenolone is from pregnenolone in the steroid pathways, the more sensitive it is to inhibition of its synthesis by pregnenolone. You can see this effect in the attached image. Lower concentrations of pregnenolone were needed to inhibit androstenedione synthesis than DHEA, since androstenedione is further away from pregnenolone. The next androgen down the line being testosterone, the pregnenolone concentration for its inhibition may be even lower than the one for androstenedione.
TLDR: In lower concentrations pregnenolone increases synthesis of both androgens and progesterone. In higher concentrations, it inhibits androgen synthesis but continues to stimulate progesterone synthesis. If the progesterone synthesis pathway becomes too dominant (as was seen with high dose pregnenolone in humans), that can lead to the anti-androgenic side effects associated with progesterone.

Variation in 3β-hydroxysteroid dehydrogenase activity and in pregnenolone supply rate can paradoxically alter androstenedione synthesis. - PubMed - NCBI
"...Results of the steady-state analysis in which supply of pregnenolone (P5) is varied between 0.01 and 10 uM/s, a sufficiently wide range to capture of all qualitative results, are shown in Fig. 5. Parameters other than P5 supply are the same as in the simulation example in Section 3.2. The curves illustrate that increasing the P5 supply rate initially increases the synthesis of all the steroids; however, when the P5 supply rate reaches a certain level, further increasing this rate will firstly suppress the synthesis of A4, then DHEA, and lastly, 17OHP4. In contrast, increasing P5 supply rate resulted in a continual increase in P4 production."

"...By taking into consideration competitive inhibition of the enzymes by substrates and products, the model shows that when the rate of P5 supply reaches a certain level, further increases in P5 supply rate will suppress the synthesis of A4, DHEA, and 17OH-P4, but not the synthesis of P4. Obviously, at low rates of P5 supply, the concentrations of all steroids are low and inhibition of P450c17 by substrates and 3-HSD by both substrates and products is negligible. Increasing the P5 supply rate progressively increases the synthesis of all the steroids to a point when the steroid concentrations reach levels that are sufficient to start inhibiting the activities ofthe both enzymes. The more reaction steps there are between the precursor substrate P5 and the end product, the stronger the effect of competitive inhibition is on its synthesis. Therefore, as the P5 supply rate increases, the suppression of A4 synthesis occurs first, following by that of DHEA and then 17OH-P4. In turn, this increasingly drives P5 flux down the 4 pathway towards the synthesis of P4. The increased flux down the 4 pathway is able to overcome the effect of the inhibition of 3-HSD by its catalytic substrates and products, allowing P4 synthesis to continue to rise with increasing P5 supply rate."

Hi haduit, I've been asking everyone but nobody can give me an answer. Why are my serum pregnenolone levels really high but my testosterone is the crapper? My DHEA

There was a recent discussion about high dose pregnenolone on the forum and some people sent Peat my comments that high dose pregnenolone can inhibit androgen synthesis. Peat replied that he has not seen such effects, but did not directly speak against the idea. Privately, I got quite a few messages accusing me of making stuff up. Well, I was not making stuff up, I was referring to an actual study and also to reports of people who found pregnenolone beyond 200mg daily killed their sex drive. Doses below 100mg had largely stimulating effect on libido and muscle tone, indicative of an androgen boost. The larger doses, as we know from the schizophrenia studies, converted mainly into progesterone and allopregnanolone.
So, here is the study suggesting that there is indeed an optimal range of pregnenolone concentration so that it stimulates the conversion of said pregnenolone down the androgen pathways. Higher than the optimal concentration was suppressive of androgen synthesis from pregnenolone. Unfortunately, the optimal pregnenolone concentrations are different for stimulating androstenedione, DHEA, and 17-OH-pregnenolone synthesis so there is no one size fits all. But I think aiming for not exceeding the optimal concentration that simulated DHEA synthesis (about 2uM) maximally would be a good compromise. Also, as you can see, pregnenolone stimulated synthesis of progesterone in any concentration. So, for androgens synthesis pregnenolone seems to have a bi-phasic effect while for progesterone it is stimulating in any dose. The latter part matches well the human studies with large doses pregnenolone.
While this study concerns mostly oral administration of pregnenolone, application to the scrotum is probably also subject to some restrictions in terms of optimal dose. Some people using the topical approach already noted that higher than 10mg dose of pregnenolone on the scrotum gave them symptoms of progesterone rather than androgen synthesis.
Finally, the study makes the claim that the further away a derivative of pregnenolone is from pregnenolone in the steroid pathways, the more sensitive it is to inhibition of its synthesis by pregnenolone. You can see this effect in the attached image. Lower concentrations of pregnenolone were needed to inhibit androstenedione synthesis than DHEA, since androstenedione is further away from pregnenolone. The next androgen down the line being testosterone, the pregnenolone concentration for its inhibition may be even lower than the one for androstenedione.
TLDR: In lower concentrations pregnenolone increases synthesis of both androgens and progesterone. In higher concentrations, it inhibits androgen synthesis but continues to stimulate progesterone synthesis. If the progesterone synthesis pathway becomes too dominant (as was seen with high dose pregnenolone in humans), that can lead to the anti-androgenic side effects associated with progesterone.

Variation in 3β-hydroxysteroid dehydrogenase activity and in pregnenolone supply rate can paradoxically alter androstenedione synthesis. - PubMed - NCBI
"...Results of the steady-state analysis in which supply of pregnenolone (P5) is varied between 0.01 and 10 uM/s, a sufficiently wide range to capture of all qualitative results, are shown in Fig. 5. Parameters other than P5 supply are the same as in the simulation example in Section 3.2. The curves illustrate that increasing the P5 supply rate initially increases the synthesis of all the steroids; however, when the P5 supply rate reaches a certain level, further increasing this rate will firstly suppress the synthesis of A4, then DHEA, and lastly, 17OHP4. In contrast, increasing P5 supply rate resulted in a continual increase in P4 production."

"...By taking into consideration competitive inhibition of the enzymes by substrates and products, the model shows that when the rate of P5 supply reaches a certain level, further increases in P5 supply rate will suppress the synthesis of A4, DHEA, and 17OH-P4, but not the synthesis of P4. Obviously, at low rates of P5 supply, the concentrations of all steroids are low and inhibition of P450c17 by substrates and 3-HSD by both substrates and products is negligible. Increasing the P5 supply rate progressively increases the synthesis of all the steroids to a point when the steroid concentrations reach levels that are sufficient to start inhibiting the activities ofthe both enzymes. The more reaction steps there are between the precursor substrate P5 and the end product, the stronger the effect of competitive inhibition is on its synthesis. Therefore, as the P5 supply rate increases, the suppression of A4 synthesis occurs first, following by that of DHEA and then 17OH-P4. In turn, this increasingly drives P5 flux down the 4 pathway towards the synthesis of P4. The increased flux down the 4 pathway is able to overcome the effect of the inhibition of 3-HSD by its catalytic substrates and products, allowing P4 synthesis to continue to rise with increasing P5 supply rate."

Hi haduit, I've been asking everyone why my blood serum pregnenolone levels are so hi but my testosterone is in the crapper. My DHEA levels seem ok to me. DHt level seem good also and progesterone so what is the problem. I wonder if I have and enzyme problem and that's why it's no converting to other hormones.

Do think a 17a-OH pregnenolone test would be a good idea? And check the enzyme CYP17A1?

 

[Gorillaquills]

There was a recent discussion about high dose pregnenolone on the forum and some people sent Peat my comments that high dose pregnenolone can inhibit androgen synthesis. Peat replied that he has not seen such effects, but did not directly speak against the idea. Privately, I got quite a few messages accusing me of making stuff up. Well, I was not making stuff up, I was referring to an actual study and also to reports of people who found pregnenolone beyond 200mg daily killed their sex drive. Doses below 100mg had largely stimulating effect on libido and muscle tone, indicative of an androgen boost. The larger doses, as we know from the schizophrenia studies, converted mainly into progesterone and allopregnanolone.
So, here is the study suggesting that there is indeed an optimal range of pregnenolone concentration so that it stimulates the conversion of said pregnenolone down the androgen pathways. Higher than the optimal concentration was suppressive of androgen synthesis from pregnenolone. Unfortunately, the optimal pregnenolone concentrations are different for stimulating androstenedione, DHEA, and 17-OH-pregnenolone synthesis so there is no one size fits all. But I think aiming for not exceeding the optimal concentration that simulated DHEA synthesis (about 2uM) maximally would be a good compromise. Also, as you can see, pregnenolone stimulated synthesis of progesterone in any concentration. So, for androgens synthesis pregnenolone seems to have a bi-phasic effect while for progesterone it is stimulating in any dose. The latter part matches well the human studies with large doses pregnenolone.
While this study concerns mostly oral administration of pregnenolone, application to the scrotum is probably also subject to some restrictions in terms of optimal dose. Some people using the topical approach already noted that higher than 10mg dose of pregnenolone on the scrotum gave them symptoms of progesterone rather than androgen synthesis.
Finally, the study makes the claim that the further away a derivative of pregnenolone is from pregnenolone in the steroid pathways, the more sensitive it is to inhibition of its synthesis by pregnenolone. You can see this effect in the attached image. Lower concentrations of pregnenolone were needed to inhibit androstenedione synthesis than DHEA, since androstenedione is further away from pregnenolone. The next androgen down the line being testosterone, the pregnenolone concentration for its inhibition may be even lower than the one for androstenedione.
TLDR: In lower concentrations pregnenolone increases synthesis of both androgens and progesterone. In higher concentrations, it inhibits androgen synthesis but continues to stimulate progesterone synthesis. If the progesterone synthesis pathway becomes too dominant (as was seen with high dose pregnenolone in humans), that can lead to the anti-androgenic side effects associated with progesterone.

Variation in 3β-hydroxysteroid dehydrogenase activity and in pregnenolone supply rate can paradoxically alter androstenedione synthesis. - PubMed - NCBI
"...Results of the steady-state analysis in which supply of pregnenolone (P5) is varied between 0.01 and 10 uM/s, a sufficiently wide range to capture of all qualitative results, are shown in Fig. 5. Parameters other than P5 supply are the same as in the simulation example in Section 3.2. The curves illustrate that increasing the P5 supply rate initially increases the synthesis of all the steroids; however, when the P5 supply rate reaches a certain level, further increasing this rate will firstly suppress the synthesis of A4, then DHEA, and lastly, 17OHP4. In contrast, increasing P5 supply rate resulted in a continual increase in P4 production."

"...By taking into consideration competitive inhibition of the enzymes by substrates and products, the model shows that when the rate of P5 supply reaches a certain level, further increases in P5 supply rate will suppress the synthesis of A4, DHEA, and 17OH-P4, but not the synthesis of P4. Obviously, at low rates of P5 supply, the concentrations of all steroids are low and inhibition of P450c17 by substrates and 3-HSD by both substrates and products is negligible. Increasing the P5 supply rate progressively increases the synthesis of all the steroids to a point when the steroid concentrations reach levels that are sufficient to start inhibiting the activities ofthe both enzymes. The more reaction steps there are between the precursor substrate P5 and the end product, the stronger the effect of competitive inhibition is on its synthesis. Therefore, as the P5 supply rate increases, the suppression of A4 synthesis occurs first, following by that of DHEA and then 17OH-P4. In turn, this increasingly drives P5 flux down the 4 pathway towards the synthesis of P4. The increased flux down the 4 pathway is able to overcome the effect of the inhibition of 3-HSD by its catalytic substrates and products, allowing P4 synthesis to continue to rise with increasing P5 supply rate."

Here are my current levels:

LH 5.07 mlU/ml
FSH 6.3 mlU/ml
DHT 210.4 pg/ml seems low
DHEA 233 ug/dl seems low
Prolactin 7.1ng/ml
Pregnenolone 321 ng/dl. High
Progesterone 1.3 ng/dl
Testosterone 300 ng/dl low
Free testosterone 5.3 ng/dl low
Estradiol 42.2 pg/ml high
Estrone 54 pg/ml
Cortisol 9.2 ug/dl
Shbg 27.5 nmoL/l
TSH 7.140 ulU/ml high
Ft3 3.3 pg/ml
Ft4 1.10 ng/ dl
Vitamin d 52 ng/dl

 

[Regina]

Here are my current levels:

LH 5.07 mlU/ml
FSH 6.3 mlU/ml
DHT 210.4 pg/ml seems low
DHEA 233 ug/dl seems low
Prolactin 7.1ng/ml
Pregnenolone 321 ng/dl. High
Progesterone 1.3 ng/dl
Testosterone 300 ng/dl low
Free testosterone 5.3 ng/dl low
Estradiol 42.2 pg/ml high
Estrone 54 pg/ml
Cortisol 9.2 ug/dl
Shbg 27.5 nmoL/l
TSH 7.140 ulU/ml high
Ft3 3.3 pg/ml
Ft4 1.10 ng/ dl
Vitamin d 52 ng/dl

TSH !!!! how are your temps and resting pulse rate?