Pregnenolone makes high dose Testosterone tolerable

[ivkonst2017]

@Nelson Vergel , you used a Pregnenolone supplement that is in a lipid matrix, that will by pass the liver, and that is why your Progesterone did not increase.

Are you sure about that?I also tried to try preg on a lipid matrix

 

[Gianluca]

Are you sure about that?I also tried to try preg on a lipid matrix

I remember using a Nutricology brand, in a lipid matrix as well. The company claimed that the lipid matrix would make the pregnenolone by pass the liver. Actually just double checking you can read the description of this Pregnenolone 50 mg Micronized Lipid Matrix 60 Scored Tabs

if we need to increase Progesterone level with Pregnenolone supplementation, we need that first pass in the liver.

 

[Anonymon]

What's pregs effect on cortisol. I've yet to find anything that helps my low normal cortisol. I'm usually around 12-14 a.m serum

This is anecdotal, but I’ve undergone cortisol replacement therapy and am actually still in a small dose of it that I’d been weening off over time. Also trying to pregnenolone cream and pill combo since last week. The cream in my case causes most of the same feelings and symptoms I get when I’m supplementing cortisol, which is actually why I’m having to change my timing of taking it because my sleep’s going to hell. Day one and I felt tired after, but soon after that I mostly felt energized. In general I feel very similarly and have telling symptoms in myself while on it when I was taking higher dose cortisol, both for better and worse.

Mine has been historically low after finasteride, so it might not affect others that way if theirs is low for other reasons. For me though, it’s felt and been similar symptomatically, though more of the positive things than the negative.

 

[Gianluca]

This is anecdotal, but I’ve undergone cortisol replacement therapy and am actually still in a small dose of it that I’d been weening off over time. Also trying to pregnenolone cream and pill combo since last week. The cream in my case causes most of the same feelings and symptoms I get when I’m supplementing cortisol, which is actually why I’m having to change my timing of taking it because my sleep’s going to hell. Day one and I felt tired after, but soon after that I mostly felt energized. In general I feel very similarly and have telling symptoms in myself while on it when I was taking higher dose cortisol, both for better and worse.

Mine has been historically low after finasteride, so it might not affect others that way if theirs is low for other reasons. For me though, it’s felt and been similar symptomatically, though more of the positive things than the negative.

I heard once dr Crisler mentioning how Dr Mark Gordon was using Pregnenolone cream to cure people with adrenal fatigue. Yet I now do not understand how that works, since the cream does not convert into the downstream metabolites

 

[Fortunate]

To add to the discussion, I went ahead and got pregnenolone levels.

My level is 19 (LC/MS) (range 22-237).

I am not sure if this range is assuming male or female.

I tried micronized pills at 50mg for a day or two and didn't feel great. On the other hand, I was also had some other variables that could have made me feel that way. I could possibly try it again, holding other variables constant. Or, maybe I non-micronized would work better.

If anyone else is having success, please share the brand and dose.

Thanks.

 

[Cataceous]

My experience: Even at relatively low doses of 7.5-15 mg/day orally the anxiogenic properties of pregnenolone dominated to the point that I could not continue supplementing. I tried on three separate occasions.

I have no such problems with DHEA, even though its sulfated form has somewhat similar properties. Wikipedia does describe pregnenolone sulfate as "a potent negative allosteric modulator of the GABA-A receptor".

 

[MarcoFL]

My experience: Even at relatively low doses of 7.5-15 mg/day orally the anxiogenic properties of pregnenolone dominated to the point that I could not continue supplementing. I tried on three separate occasions.

I have no such problems with DHEA, even though its sulfated form has somewhat similar properties. Wikipedia does describe pregnenolone sulfate as "a potent negative allosteric modulator of the GABA-A receptor".

I have had the same issues whenever I have tried to add pregnenolone I have a negative experience from it! Higher heart rate is usually the first sign to me that something is not right! I use my Apple Watch and Oura ring to help me see what supplement might not not be agreeing with my body.

 

[Gman86]

This is anecdotal, but I’ve undergone cortisol replacement therapy and am actually still in a small dose of it that I’d been weening off over time. Also trying to pregnenolone cream and pill combo since last week. The cream in my case causes most of the same feelings and symptoms I get when I’m supplementing cortisol, which is actually why I’m having to change my timing of taking it because my sleep’s going to hell. Day one and I felt tired after, but soon after that I mostly felt energized. In general I feel very similarly and have telling symptoms in myself while on it when I was taking higher dose cortisol, both for better and worse.

Mine has been historically low after finasteride, so it might not affect others that way if theirs is low for other reasons. For me though, it’s felt and been similar symptomatically, though more of the positive things than the negative.

So do u take it in the morning now, and where are u applying the preg cream? What dose are u using?

and what negatives did u get from cortisol replacement therapy? And what negatives have u noticed while on preg cream?

 

[Zibernet]

To add to the discussion, I went ahead and got pregnenolone levels.

My level is 19 (LC/MS) (range 22-237).

I am not sure if this range is assuming male or female.

I tried micronized pills at 50mg for a day or two and didn't feel great. On the other hand, I was also had some other variables that could have made me feel that way. I could possibly try it again, holding other variables constant. Or, maybe I non-micronized would work better.

If anyone else is having success, please share the brand and dose.

Thanks.

Makes my brain work really well, memory, language.
Makes me a bit too mellow and empathic with people, too agreeable to my liking.
The aggressiveness of the testosterone balances it out nicely.

 

[Anonymon]

So do u take it in the morning now, and where are u applying the preg cream? What dose are u using?

and what negatives did u get from cortisol replacement therapy? And what negatives have u noticed while on preg cream?

Today was the first day in the morning. I mostly did it on my stomach but switched to thighs. Did 50mg of the cream for a few days then added 25mg to the morning and had 50mg at night. Also did 30mg of the pill form in the morning. Now it’s strictly 50mg of cream in the morning.

For the negatives, negative thoughts will linger and be a little obsessive, generally obsessive thoughts, irritability, waking up early and unable to get back to sleep, anxiety, water retention. It affecting my sleep could have also made those worse.

 

[JA Battle]

Or maybe the failure is yours. Did you take multiple blood samples to ensure an accurate computation of area under the curve? Did you studiously inspect your injection sites to ensure no leakage? Can you be completely certain the testosterone concentrations were the same? Did you simultaneously measure SHBG to ensure it didn't change, thus altering total testosterone?

Conducting a study is a lot harder than it sounds. Just when you think you've accounted for all the confounding variables you find other ones. With anecdotes there's little attempt at such rigor. Add in a touch of subjectivity and these tales must be weighted well below decent controlled studies when it comes to credibility.

I believe injection frequently may play a role. Daily subq versus subq less frequent injections. Maybe larger doses less frequently just pool in the subq tissue. This I believe to be the biggest variable in this whole discussion

 

[Cataceous]

I believe injection frequently may play a role. Daily subq versus subq less frequent injections. Maybe larger doses less frequently just pool in the subq tissue. This I believe to be the biggest variable in this whole discussion

I think injection frequency plays a role in the accuracy of the measurements. It seems like there's a lot more "noise" in measurements where there's significant peak-trough variation. This is borne out in a study of guys on TRT, and jibes with my experience with daily propionate. In contrast, measurements while on daily or EOD doses of a longer ester seem to be quite stable, with relatively small standard deviations.

In the end, however, the total amount of testosterone absorbed is going to be close to 100%, regardless of injection frequency. It's just that accurately evaluating the areas under the curves in low-frequency protocols is challenging outside of a research setting.

When it comes to subjective results the rate of absorption is surely a significant factor. Think of injecting 200 mg cypionate once every two weeks versus 14 mg every day. It's the same average daily intake of testosterone but with vastly different serum profiles. IM vs SC isn't nearly as dramatic, but with less frequent dosing the serum profiles do differ even though total testosterone absorbed is the same.

 

[JA Battle]

I think injection frequency plays a role in the accuracy of the measurements. It seems like there's a lot more "noise" in measurements where there's significant peak-trough variation. This is borne out in a study of guys on TRT, and jibes with my experience with daily propionate. In contrast, measurements while on daily or EOD doses of a longer ester seem to be quite stable, with relatively small standard deviations.

In the end, however, the total amount of testosterone absorbed is going to be close to 100%, regardless of injection frequency. It's just that accurately evaluating the areas under the curves in low-frequency protocols is challenging outside of a research setting.

When it comes to subjective results the rate of absorption is surely a significant factor. Think of injecting 200 mg cypionate once every two weeks versus 14 mg every day. It's the same average daily intake of testosterone but with vastly different serum profiles. IM vs SC isn't nearly as dramatic, but with less frequent dosing the serum profiles do differ even though total testosterone absorbed is the same.

Yes absorption is going to be complete with Subq. There is just a different pattern to the absorption that seems to throw people off. I typically stay clear of subq because there just seems to be little benefit to doing over shallow IM and i get a very dependable absorption curve and metabolism of drug.

 

[JA Battle]

I heard once dr Crisler mentioning how Dr Mark Gordon was using Pregnenolone cream to cure people with adrenal fatigue. Yet I now do not understand how that works, since the cream does not convert into the downstream metabolites

transdermal use of hormones does not result in hormones that defy the ability to interact with necessary enzymes for conversion. Endogenously secreted pregnenolone does not have a first pass through the liver. The creams absorption is also a variable in this case. I’ve raised my progesterone and dhea with pregnenolone in dmso which has near complete absorption.

smaller doses will convert more equally to dhea and progesterone. Larger doses will favor the progesterone pathway.

 

[ivkonst2017]

IM vs SC isn't nearly as dramatic, but with less frequent dosing the serum profiles do differ even though total testosterone absorbed is the same.

I had huge differences in levels between sub q and IM on nearly identical protocols with the same ester. The only difference the sub q dose was higher and levels way lower

 

[JA Battle]

I had huge differences in levels between sub q and IM on nearly identical protocols with the same ester. The only difference the sub q dose was higher and levels way lower

this whole discussion is rather simple. Subq doesn’t have issue with absorbing. It just has a different absorption curve. It is likely slower absorbing. Maybe depending on the adipose tissue makeup, a much longer absorption. Most of our pharmacokinetic info on drugs suspended in oil is by way of IM injection. So IM is the way to go. Hopefully nobody is too fat to find a place to go IM with an insulin pin because it’s less of a pain than Subq due to many people developing little oil nodules in Subq tissue.

 

[ivkonst2017]

Subq doesn’t have issue with absorbing. It just has a different absorption curve.

I thinknif this was the only issue after enough weeks have passed the levels should become equal

 

[JA Battle]

I thinknif this was the only issue after enough weeks have passed the levels should become equal

I just want to know where the testosterone goes then. Is is excreted without being cleaved from the ester? That wouldn’t make much sense.

 

[ivkonst2017]

I just want to know where the testosterone goes then. Is is excreted without being cleaved from the ester? That wouldn’t make much sense.

Do you think anybody knows the mechanism for sure? What matters to me is that many people get higher blood levels and feel better on IM compared to sub q injections - me included and a few close people whose protocols I've observed for some longer time, their issues and struggles on TRT. This paragraph is what we know for sure.

In the next paragraph are my own thougths on the matter. Maybe its possible in fact most of the testosterone on sub q is really absorbed as well, but just on sub q it is so slow that it cannot catch up to the body's metabolisation and excretion. I also assume some of the test may remain stuck for even much longer in the sub q nodules that form after injection. As a result on sub q injections in comparison to IM the whole process of absorbtion-metabolisation and excretion is badly altered because the absorbtion process is greatly distorted. Remember all these compounds are tested and developped for IM use.

 

[bixt]

There is just too much anecdotal info pointing in the direction of subq being inferior to IM in a lot of men. These are men who have tested over time, and we cannot discount the info provided. The total sample size over multiple forums is a LOT. This anomaly cannot be ignored. To all those in difficulty dialing in, ensure IM is the method used first and foremost.

There will always be those who are too stubborn and too set in their ways to realise this.