Pregnenolone and Progesterone for Men: Pharmacokinetics and Studies

"Pregnenolone can be administered orally, subcutaneously, intravenously, intranasally, and topically/transdermally. Oral pregnenolone has high metabolism and low bioavailability.28 It is lipophilic and readily crosses the blood brain barrier.

There is very limited data on the pharmacokinetics of exogenous pregnenolone. Oral pregnenolone is metabolized in preference to allopregnanolone, rather than other hormones biosynthesized from pregnenolone substrate, such as cortisol or DHEA. One study observed that three hours after oral consumption of a single dose of 400mg of pregnenolone, pregnenolone serum levels increased by approximately 60%. Two hours after this dose, allopregnanolone serum levels tripled. An earlier study shows that a single oral dose of 175mg of pregnenolone approximately doubled pregnenolone serum levels over the course of four to eight hours.

One study observed the effects of exogenous pregnenolone on patients diagnosed with schizophrenia or schizoaffective disorder. Participants were given eight weeks of oral pregnenolone--with an escalating fixed-dose approach, where patients took 500mg per day for the last four weeks. Serum levels of pregnenolone and certain downstream metabolites were measured. Treatment with oral pregnenolone elevated pregnenolone serum levels fourfold, pregnenolone sulfate serum levels tripled, and allopregnanolone serum levels increased fivefold. Furthermore, treatment with oral pregnenolone elevated progesterone serum levels more than fourfold and DHEAS levels by approximately 16%. In this study, exogenous pregnenolone did not increase serum levels of testosterone, free testosterone, cortisol, DHEA, estradiol, or androstenedione levels."

Marx CE, Keefe RSE, et al. Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia. Neuropsychopharmacology. 2009 Jul; 34(8): 1885–1903.

Note from Nelson

Anabolic steroids and TRT decrease SHBG, DHEA, pregnenolone and progesterone in men.

Response of serum testosterone and its precursor steroids, SHBG and CBG to anabolic steroid and testosterone self-administration in man. Ruokonen A, et al. J Steroid Biochem. 1985. Abstract The influence of high doses of testosterone and anabolic steroids on testicular endocrine function...

www.excelmale.com

If men on TRT have undetectable or very low pregnenolone due to the LH shut down caused by TRT, then a dose close to 100 mg per day may actually increase pregnenolone blood levels one fold.
I am particularly interested in pregnenolone's boosting effect on allopregnanolone:

Allopregnanolone in mood disorders

ABSTRACT The neuroactive steroid allopregnanolone (ALLO) is an endogenous positive allosteric modulator of GABA type A receptor (GABAAR), and the down-regulation of its biosynthesis has been attributed to the development of mood disorders, such as depression, anxiety, and post-traumatic stress...

www.excelmale.com

Allopregnanolone - Wikipedia

en.wikipedia.org

Allopregnanolone Elevations Following Pregnenolone Administration are Associated with Enhanced Activation of Emotion Regulation Neurocircuits - PMC

The neurosteroid allopregnanolone is a potent allosteric modulator of the GABA(A) receptor with anxiolytic properties. Exogenous administration of allopregnanolone reduces anxiety, and allopregnanolone blockade impairs social and affective ...

www.ncbi.nlm.nih.gov

Pharmacology of pregnenolone and progesterone:

"Oral administration of 50 or 100 mg pregnenolone has been found to have minimal or negligible effect on urinary levels of testosterone and testosterone metabolites, including of androsterone, etiocholanolone, 5-androstanediol, androstadienol, and androstenol (and/or their conjugates), and this suggests that only a small amount of pregnenolone is converted into testosterone.[17][18] This is in accordance with findings on the conversion of DHEA into testosterone, in which only 1.5% of an oral dose of DHEA was found to be converted into testosterone.[17] In contrast to the androstanes, 50 or 100 mg oral pregnenolone has been found to significantly and in fact "strongly" increase urinary levels of the progesterone metabolites pregnanediol and pregnanolone (and/or their conjugates), whereas pregnanetriol was unaffected.[17][18] Unlike the case of oral administration, transdermal administration of 30 mg/day pregnenolone cream has not been found to affect urinary levels of metabolites of any other steroids, including of progesterone.[18]"

Pregnenolone - Wikipedia

 

So is the general consensus that pregnenolone has anti-anxiety benefits or pro-anxiety since it seems it can antagonize or agonize the gaba receptors?

 

What is your nandrolone protocol ie dosage, 1 injection/week? 2 split doses? I have a bunch on hand and haven’t started it yet. I’m thinking of using 100mg week, but I just haven’t pulled the trigger yet because I’m feeling excellent and don’t want to muddy the waters so to speak.

Since starting nandrolone I’ve always injected it EOD. I just keep it simple and inject both my nandrolone and testosterone at the same time EOD. I draw each one up in their own syringes, and inject IM into the outter 3rd of my thighs where the skin and fat is the thinnest. I’m currently doing 100mg/ week of nandrolone along with my 175mg of test/ week.

What reason(s) make u want to add nandrolone? If I were u, and felt amazing, I honestly probably wouldn’t mess with ur protocol.

 

Since starting nandrolone I’ve always injected it EOD. I just keep it simple and inject both my nandrolone and testosterone at the same time EOD. I draw each one up in their own syringes, and inject IM into the outter 3rd of my thighs where the skin and fat is the thinnest. I’m currently doing 100mg/ week of nandrolone along with my 175mg of test/ week.

What reason(s) make u want to add nandrolone? If I were u, and felt amazing, I honestly probably wouldn’t mess with ur protocol.

Just to add a small performance boost to my workouts ie increased anabolism and recovery. I’m strictly on Cyp right now for the next 4 months.

 

Just to add a small performance boost to my workouts ie increased anabolism and recovery. I’m strictly on Cyp right now for the next 4 months.

U looking to add something indefinitely to boost anabolism and recovery, or something just to run for a little bit and then take a break, and possibly repeat indefinitely?

What’s ur IGF-1 level? Have u thought about optimizing ur growth hormone levels to improve anabolism and recovery? It would mostly improve recovery, but with anabolics it tends to have a 1+1=3 effect. Much greater benefit than optimizing growth hormone levels without being on any anabolics. With the improved recovery, and I believe it increasing the number of satelite cells, u will notice an increase in lean body mass over time. It can also tend to “fill out” the muscle that u already have

 

U looking to add something indefinitely to boost anabolism and recovery, or something just to run for a little bit and then take a break, and possibly repeat indefinitely?

What’s ur IGF-1 level? Have u thought about optimizing ur growth hormone levels to improve anabolism and recovery? It would mostly improve recovery, but with anabolics it tends to have a 1+1=3 effect. Much greater benefit than optimizing growth hormone levels without being on any anabolics. With the improved recovery, and I believe it increasing the number of satelite cells, u will notice an increase in lean body mass over time. It can also tend to “fill out” the muscle that u already have

How do we optimize gh?

 

U looking to add something indefinitely to boost anabolism and recovery, or something just to run for a little bit and then take a break, and possibly repeat indefinitely?

What’s ur IGF-1 level? Have u thought about optimizing ur growth hormone levels to improve anabolism and recovery? It would mostly improve recovery, but with anabolics it tends to have a 1+1=3 effect. Much greater benefit than optimizing growth hormone levels without being on any anabolics. With the improved recovery, and I believe it increasing the number of satelite cells, u will notice an increase in lean body mass over time. It can also tend to “fill out” the muscle that u already have

Yes I’m looking for something to run indefinitely but take breaks from when I run a cycle.

I do not know my IGF-1 levels but I’m certainly all ears when it comes to optimizing. This is territory that I’m not versed in at all. I have never used SARMS or GH to optimize my IGF -1 levels and you have really piqued my interest. I’d love to hear about compounds you’ve actually used, dosages and what you feel is best. Thanks Gman!

 

Since starting nandrolone I’ve always injected it EOD. I just keep it simple and inject both my nandrolone and testosterone at the same time EOD. I draw each one up in their own syringes, and inject IM into the outter 3rd of my thighs where the skin and fat is the thinnest. I’m currently doing 100mg/ week of nandrolone along with my 175mg of test/ week.

What reason(s) make u want to add nandrolone? If I were u, and felt amazing, I honestly probably wouldn’t mess with ur protocol.

How’s libido?

 

How’s libido?

Libido is probably around a 6/10 imo. When I’m with my gf in person I get turned on plenty, and erections are great, so it’s not that bad. I personally just prefer my libido to be as close to a 10/10 as I can get it. I find that I just feel better overall whenever libido is really high. It almost seems to be an indicator for me that everything is functioning optimally, not just sexually. I also found out a long time ago that when my libido is really high, I fall asleep quicker, due to just thinking about sex while trying to go to sleep. The lower my libido, the more I think of other things going on in my life when I’m trying to go to sleep, which tends to keep me awake. But anytime I’m solely thinking about sex before bed, I fall asleep very quickly. I haven’t had a day off from work this year, and I have a lot of stressful things going on in my life atm, which I think are preventing my libido from being higher than it is. But luckily it’s still at a level where it doesn’t take away from sexual relations with the gf. Everything in that department with her is about as good as it can get, thank god. Long answer to a very simple question lol

 

Libido is probably around a 6/10 imo. When I’m with my gf in person I get turned on plenty, and erections are great, so it’s not that bad. I personally just prefer my libido to be as close to a 10/10 as I can get it. I find that I just feel better overall whenever libido is really high. It almost seems to be an indicator for me that everything is functioning optimally, not just sexually. I also found out a long time ago that when my libido is really high, I fall asleep quicker, due to just thinking about sex while trying to go to sleep. The lower my libido, the more I think of other things going on in my life when I’m trying to go to sleep, which tends to keep me awake. But anytime I’m solely thinking about sex before bed, I fall asleep very quickly. I haven’t had a day off from work this year, and I have a lot of stressful things going on in my life atm, which I think are preventing my libido from being higher than it is. But luckily it’s still at a level where it doesn’t take away from sexual relations with the gf. Everything in that department with her is about as good as it can get, thank god. Long answer to a very simple question lol

I appreciate it. I’ve not been able to sustain a solid libido on TRT. I do cream shot combo. Mine is about a 3 or 4 out of 10. Occasionally libido spikes to a 7 or 8 but I’m with you. The higher the libido the happier I am. When it’s low, Its on my mind way too much that it’s low.

 

Yes I’m looking for something to run indefinitely but take breaks from when I run a cycle.

I do not know my IGF-1 levels but I’m certainly all ears when it comes to optimizing. This is territory that I’m not versed in at all. I have never used SARMS or GH to optimize my IGF -1 levels and you have really piqued my interest. I’d love to hear about compounds you’ve actually used, dosages and what you feel is best. Thanks Gman!

I have never tried any SARMS, and don’t really see myself ever trying any, but u never know. They’re just too new and I don’t see any need for them for me atm, with all the HRT options we have available to us.

I tried growth hormone peptides for a few years, specifically an ipamorelin and cjc-1295 without DAC combo. Never noticed any benefits from using it. Also didn’t increase my IGF-1 even a little bit. Have heard, however, that even tho it won’t raise igf-1 in the serum, that it’s still acting on growth hormone receptors within the body. Not sure if that’s true or not.

I’m currently using generic HGH, and have verified via labs that it’s working very nicely so far. Haven’t noticed much subjectively I don’t think yet. Maybe sleeping a bit better, my muscles possibly feel a little more filled out, muscles possibly feel a little more pumped during workouts. But those things could be due to the nandrolone and test that I’m taking, so hard to say. A lot of the benefits from HGH supposedly take months to really notice. I plan on running HGH indefinitely. But once it fully kicks in the benefits seem pretty amazing. People report it being easier to keep fat off, muscles appear filled out more, more energy, some lean muscle tissue gains over time, and then all the other non bodybuilding related benefits, like better hair, nails, skin, etc. Just a really good addition to any HRT protocol, imo. Especially as u get older and IGF-1 levels continue to drop.

 

I have never tried any SARMS, and don’t really see myself ever trying any, but u never know. They’re just too new and I don’t see any need for them for me atm, with all the HRT options we have available to us.

I tried growth hormone peptides for a few years, specifically an ipamorelin and cjc-1295 without DAC combo. Never noticed any benefits from using it. Also didn’t increase my IGF-1 even a little bit. Have heard, however, that even tho it won’t raise igf-1 in the serum, that it’s still acting on growth hormone receptors within the body. Not sure if that’s true or not.

I’m currently using generic HGH, and have verified via labs that it’s working very nicely so far. Haven’t noticed much subjectively I don’t think yet. Maybe sleeping a bit better, my muscles possibly feel a little more filled out, muscles possibly feel a little more pumped during workouts. But those things could be due to the nandrolone and test that I’m taking, so hard to say. A lot of the benefits from HGH supposedly take months to really notice. I plan on running HGH indefinitely. But once it fully kicks in the benefits seem pretty amazing. People report it being easier to keep fat off, muscles appear filled out more, more energy, some lean muscle tissue gains over time, and then all the other non bodybuilding related benefits, like better hair, nails, skin, etc. Just a really good addition to any HRT protocol, imo. Especially as u get older and IGF-1 levels continue to drop.

My libido and erection quality have always been really good on 3iu/day HGH.
Much better than on any dose of testosterone or proviron.

 

My libido and erection quality have always been really good on 3iu/day HGH.
Much better than on any dose of testosterone or proviron.

Interesting. Do u take it in am or pm? Are u currently taking it? Is it pharma grade or generic UGL?

 

Interesting. Do u take it in am or pm? Are u currently taking it? Is it pharma grade or generic UGL?

I use Pfizer's Genotropin right before bed.
Not using it at the moment but have 2 pens in the fridge so I might pull the trigger any time.
I've used Hygetropin with similar results, but they induced more bloat.

 

I use Pfizer's Genotropin right before bed.
Not using it at the moment but have 2 pens in the fridge so I might pull the trigger any time.
I've used Hygetropin with similar results, but they induced more bloat.

How much did Pfizer’s genotropin cost u? Is hygetropin generic?

Did u have igf-1 tested on both? Or they both just gave u similar subjective benefits, with hygetropin eliciting more bloat?

 

How much did Pfizer’s genotropin cost u? Is hygetropin generic?

Genotropin 36iu pen costs me 200usd online, no script, straight from Turkey.
Hygetropin is a Chinese "pharma", or as close as it gets to pharma.

 

I always wait at least 4 weeks to make conclusions since the placebo effect can last a while. I would say I am sleeping more deeply and waking up less tired so far. No extra bloating.

I will get my lab test results (preg, prog, etc) next week after supplementing 100 mg preg every night for the past 3 weeks. I have baseline levels to compare.

Did you ever get tested and post the results? If so would you post the results or link to the thread where you posted them? Also wondering if you know of any studies or references that illustrate how exogenous supplementation of pregnenolone and/or dhea affects endogenous production. Have never seen anything referencing that aspect and I imagine they probably don’t exist, but if they do you’d be the person to ask so figured it’s worth a shot.

 

So is the general consensus that pregnenolone has anti-anxiety benefits or pro-anxiety since it seems it can antagonize or agonize the gaba receptors?

It was anti anxiety for me. Gave me a clearer head and helped me sleep at first. Then theses benefits seemed to fade after about 2 weeks. Also, all my numbers went up including estrogen and estradiol, having a negative affect on my libido. So I quit.

 

It was anti anxiety for me. Gave me a clearer head and helped me sleep at first. Then theses benefits seemed to fade after about 2 weeks. Also, all my numbers went up including estrogen and estradiol, having a negative affect on my libido. So I quit.

Any theories on why it effected libido negatively?

 

Any theories on why it effected libido negatively?

I’m guessing because it drove up estrogen and Estradiol. I feel better, libido wise, off it for sure.

 

Any theories on why it effected libido negatively?

I would guess because the increase in Progesterone