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

 

Ok. I hear you. Crisler did an interview years ago that said it made a huge difference in many of his patients lives even if they were within normal range. I’ll probably look into it because just about every afternoon I crash hard around 4:30.

Did crisler say how he treated those people for their cortisol issues? I would love to optimize my levels, but just not open to using any of the synthetic medications to do so. Is there such thing as bio-identical cortisol that someone could take?

 

Did crisler say how he treated those people for their cortisol issues? I would love to optimize my levels, but just not open to using any of the synthetic medications to do so. Is there such thing as bio-identical cortisol that someone could take?

Yes. There is bio-identical. He said 5-10mg in am and 5-10 mg pm when start to crash.

 

Yes. There is bio-identical. He said 5-10mg in am and 5-10 mg pm when start to crash.

SHR # 2071 :: Pregnenolone the Progenitor Hormone ::

 

SHR # 2071 :: Pregnenolone the Progenitor Hormone ::

They start off talking about Pregnenolone but quickly move to adrenal fatigue being treated with cortisol.

 

Yes. There is bio-identical. He said 5-10mg in am and 5-10 mg pm when start to crash.

What’s the latest in the PM you take the HC?

 

They start off talking about Pregnenolone but quickly move to adrenal fatigue being treated with cortisol.

Half way through and this is really great stuff so far. Thanks a bunch for linking it. I remember reading something years ago about how pregnenolone was widely used for things that we now use corticosteroids for. Once they were able to patent a medication that basically acted as cortisol, they stopped using pregnenolone as much. They go over this exact thing at the beginning of the podcast. Reading that article years ago always made me wonder if I could use pregnenolone to increase cortisol naturally. But when u try to research about this it’s hard to get a straight answer. Some sources say it raises cortisol, some say it decreases cortisol, king of like an adaptogen. It does one or the other depending on what u need. Which never sat well with me. Gonna go listen to the rest of the podcast. Think I’m gonna start using the topical pregnenolone I have tomorrow morning tho

 

What’s the latest in the PM you take the HC?

I only did it a short time bc of $. But around 4pm.

 

Half way through and this is really great stuff so far. Thanks a bunch for linking it. I remember reading something years ago about how pregnenolone was widely used for things that we now use corticosteroids for. Once they were able to patent a medication that basically acted as cortisol, they stopped using pregnenolone as much. They go over this exact thing at the beginning of the podcast. Reading that article years ago always made me wonder if I could use pregnenolone to increase cortisol naturally. But when u try to research about this it’s hard to get a straight answer. Some sources say it raises cortisol, some say it decreases cortisol, king of like an adaptogen. It does one or the other depending on what u need. Which never sat well with me. Gonna go listen to the rest of the podcast. Think I’m gonna start using the topical pregnenolone I have tomorrow morning tho

Anytime. Yes, def good info. Hope it works for you. Preg just killed my libido eventually but gave me clarity and good sleep for two weeks.

 

Anytime. Yes, def good info. Hope it works for you. Preg just killed my libido eventually but gave me clarity and good sleep for two weeks.

Any ideas why it dropped libido so much? What form were u taking and what was ur dose? What time of day did u take it?

 

Any ideas why it dropped libido so much? What form were u taking and what was ur dose? What time of day did u take it?

I think we talked about this on another thread. My estradiol shot up. I applied 25 mg per night shortly before bed topical to my chest.

 

So im not very familiar pregenolone and I’m just trying to catch up. Do you take it in place of hcg or at the same time ? Or is it unrelated?

 

So im not very familiar pregenolone and I’m just trying to catch up. Do you take it in place of hcg or at the same time ? Or is it unrelated?

Some people take it in place of hCG. Some take it at the same time. All depends on how you feel.

 

You have nothing to lose. I would start at 100 mg nightly and see how you feel. It may have some calming effect on you.

I am going to try this. I’ve been having some intermittent anxiety - mind racing - and have always dealt with sleep issues (I sleep very soundly but wake up every 1-1.5 hours all night long).

I assume there would be no desensitizing from the dose or any withdrawal if you stopped taking it?

 

Great post Nelson. Oral Progesterone is probably a more powerful tool to increase Allopregnenolone than Pregnenolone itself

You can now but oral allopregnenolone from AlloP

 

I started 100 mg pregnenolone 6 months ago. I took an oral supplement and also tried the Empower pharmacy prescription capsules (100 mg each). My pregnenolone blood level went from nil to 95 ng/dL with either one of them. I am not sure I felt any different. Sleep seemed a lot deeper, but not every night. Mood was good but I cannot honestly say if it was due to the pregnenolone. My language fluidity also seemed much improved.

I increased my dose to 300 mg per night since most studies used 400 mg/day. It took me weeks to realize that the higher blood pressure issues that I was experiencing were due to this dose. I had to start taking a combo of a diuretic plus a calcium channel blocker.

I realized that the 300 mg pregnenolone may be the cause for my higher blood pressure.

I stopped the higher dose pregnenolone a week ago and my blood pressure is back to normal now.

I searched for increased blood pressure in different studies and found the opposite (500 mg/day):

"According to these earlier reports, pregnenolone was very well tolerated with minimal side effects, and did not affect weight, heart rate, blood pressure (even in patients with hypertension), menstrual cycle, or glucose levels (either in diabetics or non-diabetics)."

Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia - PMC

The neurosteroid pregnenolone and its sulfated derivative enhance learning and memory in rodents. Pregnenolone sulfate also positively modulates NMDA receptors and could thus ameliorate hypothesized NMDA receptor hypofunction in schizophrenia. ...

www.ncbi.nlm.nih.gov

I bet if I had taken it with progesterone, this higher blood pressure may not have happened. I may try that combo in the future but I am still debating what is the best progesterone dose and route of administration.

Weill Cornell Researcher Shows How Progesterone Is Not Just Sex Hormone but Blood Pressure Hormone | NYP

Research from Weill Medical College of Cornell University and other institutions provides new evidence that the sex steroid hormone progesterone is also a vasoactive hormone that directly affects blood vessels. This finding sheds light on both the drop in blood pressure that usually accompanies...

www.nyp.org

 

I started 100 mg pregnenolone 6 months ago. I took an oral supplement and also tried the Empower pharmacy prescription capsules (100 mg each). My pregnenolone blood level went from nil to 95 ng/dL with either one of them. I am not sure I felt any different. Sleep seemed a lot deeper, but not every night. Mood was good but I cannot honestly say if it was due to the pregnenolone. My language fluidity also seemed much improved.

I increased my dose to 300 mg per night since most studies used 400 mg/day. It took me weeks to realize that the higher blood pressure issues that I was experiencing were due to this dose. I had to start taking a combo of a diuretic plus a calcium channel blocker.

I realized that the 300 mg pregnenolone may be the cause for my higher blood pressure.

I stopped the higher dose pregnenolone a week ago and my blood pressure is back to normal now.

I searched for increased blood pressure in different studies and found the opposite (500 mg/day):

"According to these earlier reports, pregnenolone was very well tolerated with minimal side effects, and did not affect weight, heart rate, blood pressure (even in patients with hypertension), menstrual cycle, or glucose levels (either in diabetics or non-diabetics)."

Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia - PMC

The neurosteroid pregnenolone and its sulfated derivative enhance learning and memory in rodents. Pregnenolone sulfate also positively modulates NMDA receptors and could thus ameliorate hypothesized NMDA receptor hypofunction in schizophrenia. ...

www.ncbi.nlm.nih.gov

I bet if I had taken it with progesterone, this higher blood pressure may not have happened. I may try that combo in the future but I am still debating what is the best progesterone dose and route of administration.

Weill Cornell Researcher Shows How Progesterone Is Not Just Sex Hormone but Blood Pressure Hormone | NYP

Research from Weill Medical College of Cornell University and other institutions provides new evidence that the sex steroid hormone progesterone is also a vasoactive hormone that directly affects blood vessels. This finding sheds light on both the drop in blood pressure that usually accompanies...

www.nyp.org

Do u know if empowers preg raised ur progesterone level at all?

 

I started 100 mg pregnenolone 6 months ago. I took an oral supplement and also tried the Empower pharmacy prescription capsules (100 mg each). My pregnenolone blood level went from nil to 95 ng/dL with either one of them. I am not sure I felt any different. Sleep seemed a lot deeper, but not every night. Mood was good but I cannot honestly say if it was due to the pregnenolone. My language fluidity also seemed much improved.

I increased my dose to 300 mg per night since most studies used 400 mg/day. It took me weeks to realize that the higher blood pressure issues that I was experiencing were due to this dose. I had to start taking a combo of a diuretic plus a calcium channel blocker.

I realized that the 300 mg pregnenolone may be the cause for my higher blood pressure.

I stopped the higher dose pregnenolone a week ago and my blood pressure is back to normal now.

I searched for increased blood pressure in different studies and found the opposite (500 mg/day):

"According to these earlier reports, pregnenolone was very well tolerated with minimal side effects, and did not affect weight, heart rate, blood pressure (even in patients with hypertension), menstrual cycle, or glucose levels (either in diabetics or non-diabetics)."

Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia - PMC

The neurosteroid pregnenolone and its sulfated derivative enhance learning and memory in rodents. Pregnenolone sulfate also positively modulates NMDA receptors and could thus ameliorate hypothesized NMDA receptor hypofunction in schizophrenia. ...

www.ncbi.nlm.nih.gov

I bet if I had taken it with progesterone, this higher blood pressure may not have happened. I may try that combo in the future but I am still debating what is the best progesterone dose and route of administration.

Weill Cornell Researcher Shows How Progesterone Is Not Just Sex Hormone but Blood Pressure Hormone | NYP

Research from Weill Medical College of Cornell University and other institutions provides new evidence that the sex steroid hormone progesterone is also a vasoactive hormone that directly affects blood vessels. This finding sheds light on both the drop in blood pressure that usually accompanies...

www.nyp.org

Pregnenolone 300mg per day seems a bit too much, to my understanding most guys do well with 50/100mg. I tried once 150mg oral capsule from empower, and my anxiety increased. I have been doing pretty good lately with Progesterone/Pregnenolone cream combo, 12.5mg Progesterone and 50mg Pregnenolone, I'm going to try 25mg Progesterone soon, 50mg pregnenolone cream seems enough. I like this combo to raise Progesterone better than Pregnenolone capsule

 

What is anyone's experience with how long before sleep to rub on progesterone cream? I was wondering how long it takes to absorb and when might be the peak level?

(I did read through this sub, but most times posters just say something general like at night, I couldn't sus out the timing.)

BTW, I have gotten dizzy during the day from overdosing on progesterone, very weird type of dizzy, like a max headroom experience.

 

Pregnenolone 300mg per day seems a bit too much, to my understanding most guys do well with 50/100mg. I tried once 150mg oral capsule from empower, and my anxiety increased. I have been doing pretty good lately with Progesterone/Pregnenolone cream combo, 12.5mg Progesterone and 50mg Pregnenolone, I'm going to try 25mg Progesterone soon, 50mg pregnenolone cream seems enough. I like this combo to raise Progesterone better than Pregnenolone capsule

Seems like everyone processes it a little differently. I’ve tried much lower doses of oral pregnenolone from the good brands recommended here and others, but didn’t have much luck in terms of how I felt or serum levels on blood tests. Been doing great with 400mg though, all at once in the morning. I’ve tried lowering it but it’s a clear dose response relationship for me, and works well when combined with T3 (22-30mcg a day). Feels like the good benefits I got from hydrocortisone but without the downsides, other than it being more expensive than testosterone. Cleared up some eczema too, and helped with the issues I have retaining water and being hydrated.

I don’t think many people need that much, but at least for me coming from a PFS background, it’s been wonderful.

 

I have bad news to report about my experience with pregnenolone (100 mg per night up to 300 mg per night).

During the past few months while using it I had to up my dose of blood pressure meds since my BP was increasing dramatically (no changes in weight, stress, hormones, etc).

I decided to stop the pregnenolone and 2 days later my BP was back to baseline. That has remained so for two weeks even as I scaled back my HTN treatment.

Pregnenolone can potentially have an effect on aldosterone and cortisol. I am not sure if this explains my increased BP.

I will report in a few weeks to make sure this is not just a coincidence.