Pregnenolone and Progesterone for Men: Pharmacokinetics and Studies

[Nelson Vergel]

"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

 

[Nelson Vergel]

A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression​

Neuropsychopharmacology. 2014 Nov; 39(12): 2867–2873.

Abstract
Depression in bipolar disorder (BPD) is challenging to treat. Therefore, additional medication options are needed. In the current report, the effect of the neurosteroid pregnenolone on depressive symptoms in BPD was examined. Adults (n=80) with BPD, depressed mood state, were randomized to pregnenolone (titrated to 500 mg/day) or placebo, as add-on therapy, for 12 weeks. Outcome measures included the 17-item Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptomatology—Self-Report (IDS-SR), Hamilton Rating Scale for Anxiety (HRSA), and Young Mania Rating Scale (YMRS). Serum neurosteroid levels were assessed at baseline and week 12. Data were analyzed using a mixed model ANCOVA with a between factor of treatment assignment, a within factor (repeated) of visit, and the baseline value, as well as age and gender, as covariates. In participants with at least one postbaseline visit (n=73), a significant treatment by week interaction for the HRSD (F(5,288)=2.61, p=0.025), but not IDS-SR, was observed. Depression remission rates were greater in the pregnenolone group (61%) compared with the placebo group (37%), as assessed by the IDS-SR (χ2(1)=3.99, p=0.046), but not the HRSD. Large baseline-to-exit changes in neurosteroid levels were observed in the pregnenolone group but not in the placebo group. In the pregnenolone group, baseline-to-exit change in the HRSA correlated negatively with changes in allopregnanolone (r(22)=−0.43, p=0.036) and pregNANolone (r(22)=−0.48, p=0.019) levels. Pregnenolone was well tolerated. The results suggest that pregnenolone may improve depressive symptoms in patients with BPD and can be safely administered.

A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression - PMC

Depression in bipolar disorder (BPD) is challenging to treat. Therefore, additional medication options are needed. In the current report, the effect of the neurosteroid pregnenolone on depressive symptoms in BPD was examined. Adults (n=80) with BPD, ...

www.ncbi.nlm.nih.gov

 

[Nelson Vergel]

Click on tables to see details

 

[Nelson Vergel]

Dose titrated to 500 mg per day.

Pregnenolone reduces depression- Placebo controlled study

A randomized, double-blind, placebo-controlled trial of pregnenolone for bipolar depression by Brown, E Sherwood; Park, John; Marx, Christine E; Hynan, Linda S; Gardner, Claire; Davila, Domingo; Nakamura, Alyson; Sunderajan, Prabha; Lo, Alexander; Holmes, Traci Neuropsychopharmacology. 2014...

www.excelmale.com

 

[Nelson Vergel]

Sensitive pregnenolone test you can buy

Pregnenolone Lab Test at Discounted Labs

Pregnenolone test

www.discountedlabs.com

 

[Gianluca]

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

 

[anix]

I use progesterone cream as an anxylotic and NAC as well. They help little. Im medically refractory MDD and BP. Ive been doing reading one Pregnenolone for cognitive and TBI benefit. My stuff are TBI related. Likely why I dont respond to the meds I was on for years. Thks for this post.

 

[Nelson Vergel]

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

How much do you take? I tried it for a while but I retained too much water. It may be worth another try.

I have been taking 100 mg pregnenolone every night for a week. It may be too early to tell (placebo effect?), but I am sleeping well and my mood and energy have improved. Let's see if this effect is only happening by chance!

I am also taking iron plus vitamin C (1000 mg) to improve my low ferritin (it was 34 when I lasted checked)

 

[Gman86]

How much do you take? I tried it for a while but I retained too much water. It may be worth another try.

I have been taking 100 mg pregnenolone every night for a week. It may be too early to tell (placebo effect?), but I am sleeping well and my mood and energy have improved. Let's see if this effect is only happening by chance!

I am also taking iron plus vitamin C (1000 mg) to improve my low ferritin (it was 34 when I lasted checked)

What brand of Pregnenolone are u taking?

 

[Gianluca]

I use progesterone cream as an anxylotic and NAC as well. They help little. Im medically refractory MDD and BP. Ive been doing reading one Pregnenolone for cognitive and TBI benefit. My stuff are TBI related. Likely why I dont respond to the meds I was on for years. Thks for this post.

do you use the cream on a daily basis or as needed? capsule may work better as an anxiolytic, it should convert more into allopregnenolone because the first pass in the liver

 

[Gianluca]

How much do you take? I tried it for a while but I retained too much water. It may be worth another try.

I have been taking 100 mg pregnenolone every night for a week. It may be too early to tell (placebo effect?), but I am sleeping well and my mood and energy have improved. Let's see if this effect is only happening by chance!

I am also taking iron plus vitamin C (1000 mg) to improve my low ferritin (it was 34 when I lasted checked)

I have been experimenting for a little bit with 5mg micronized cap from Empower, it has a mild sedating effect for me, it helped me with social anxiety better than Pregnenolone I believe, but still need to experiment more to confirm this. With the 5mg I did not notice any water retention or decrease libido/sex drive. I tried 10mg for the past two days at night, and the sedating effect definitely increased.

That sounds like you getting the good side effects of Pregnenolone! I have personally seen with myself within a week/10 days the effect of oral neurosteroids stabilizing, that may not be placebo

why not eating red meat regularly for Iron instead of the supplement? in my opinion is a better choice. I have seen my Ferritin increasing over the time when I started to use about 3gr or more of pure ascorbic acid, and I even take it on an empty stomach

 

[Nelson Vergel]

What brand of Pregnenolone are u taking?

I just got my pre-pregnenolone supplementation level (by LC/MS assay). My pregnenolone test level was 11 ng/dL (Quest "normal" range 22-237 ng/dL). I will retest in a few weeks after taking 100 mg every night. My progesterone test level (immunoassay) was 0.7 ng/mL (no range given). Let's see how much progesterone increases due to pregnenolone supplementation.

 

[Nelson Vergel]

I created this panel to look at upstream and downstream hormones for men on TRT:

Hormone Panel for Men on TRT- Comprehensive

This hormone panel for men on testosterone replacement therapy (TRT) contains upstream and downstream hormones to testosterone. TRT has been shown to decrease upstream hormones like pregnenolone and progesterone, and slightly decrease DHEA. Downstream ho

www.discountedlabs.com

 

[DixieWrecked]

View attachment 14631

I just got my pre-pregnenolone supplementation level (by LC/MS assay). My pregnenolone test level was 11 ng/dL (Quest "normal" range 22-237 ng/dL). I will retest in a few weeks after taking 100 mg every night. My progesterone test level (immunoassay) was 0.7 ng/mL (no range given). Let's see how much progesterone increases due to pregnenolone supplementation.

You are a saint. I am excited to see the data.

 

[Gman86]

View attachment 14631

I just got my pre-pregnenolone supplementation level (by LC/MS assay). My pregnenolone test level was 11 ng/dL (Quest "normal" range 22-237 ng/dL). I will retest in a few weeks after taking 100 mg every night. My progesterone test level (immunoassay) was 0.7 ng/mL (no range given). Let's see how much progesterone increases due to pregnenolone supplementation.

I love when guys get labs before and after trying things, can’t wait to see how the 100mg of pregnenolone effects ur pregnenolone and progesterone levels.

The range for progesterone is usually (0.0-0.5 ng/ml). It used to be (0.0-1.0). So ur level is actually quite good. From my understanding a good range to keep progesterone in would be between 0.8-1.2, for males. I’m assuming ur level is decent due to the HCG that ur taking. Mine usually comes back around 0.1 ng/ml on testosterone alone. HCG has brought it up quite a bit in the past, I forget exactly how much HCG raised it. Would have to look back at old labs

This was a pretty good quick video on progesterone lab testing, IIRC. I think he likes to see males around the 1.2 ng/ml range, again if IIRC

 

[Fortunate]

@DixieWrecked, are you still taking Pregnenolone? If so, can you tell us about your dose and experience? Do you take it in the AM? Do you also take DHEA? I have some experience with DHEA (makes me tired), but have not tried Pregnenolone. I have an interest in trying it. Sometimes but not always, I get brain fog after Test injections. I am considering running Test without hCG to see if that makes a difference, but am also considering Pregnenolone based on what I am reading here and elsewhere.

On the other hand, some have reported really bad experiences with Pregnenolone. Would love to hear how other guys are doing on it.

 

[Nelson Vergel]

The range for progesterone is usually (0.0-0.5 ng/ml). It used to be (0.0-1.0). So ur level is actually quite good. From my understanding a good range to keep progesterone in would be between 0.8-1.2, for males. I’m assuming ur level is decent due to the HCG that ur taking. Mine usually comes back around 0.1 ng/ml on testosterone alone. HCG has brought it up quite a bit in the past, I forget exactly how much HCG raised it. Would have to look back at old labs

Make sure you get the progesterone LC/MS test, not the immunoassay one.

Progesterone test (LC/MS)

Progesterone blood test for men and women

www.discountedlabs.com

 

[Gman86]

Make sure you get the progesterone LC/MS test, not the immunoassay one.

Progesterone test (LC/MS)

Progesterone blood test for men and women

www.discountedlabs.com

What’s the reference range for the progesterone LC/MS test through discounted labs? I tried getting the LC/MS version through labcorp, but didn’t like the reference range they used, so I switched back to the regular immunoassay. Their LC/MS test used the whole less than a certain number range, which I hate. Here’s the LC/MS lab that I got done through labcorp

503658: Progesterone, Free, With Total Progesterone, LC/MS-MS (Endocrine Sciences) | Labcorp

Labcorp test details for Progesterone, Free, With Total Progesterone, LC/MS-MS (Endocrine Sciences)

www.labcorp.com

 

[JA Battle]

I am reintroducing pregenolone topically suspended in dmso at 2mg on scrotum every 8 hours.

I do this because my stint of running dhea and progesterone has me in what I would describe as a “gaba dominant” state. I’m happy and don’t care about anything! Including sex and work. I’m professionally chilling

does anyone know any information relating to how much pregnenolone an adult male endogenously secretes daily? Also is it in a diurnal fashion?

on another note but not to change the course of the thread, I was with a buddy last night at a bar and he is like 6’ 180 at 7% bodyfat. He has been on 200mg test e and 200mg tren e for 5 years straight! He looks like a cartoon. And the aggression he has socially is insane. Too bad it will be short lived for him and he doesn’t notice or care.

 

[DixieWrecked]

I am reintroducing pregenolone topically suspended in dmso at 2mg on scrotum every 8 hours.

I do this because my stint of running dhea and progesterone has me in what I would describe as a “gaba dominant” state. I’m happy and don’t care about anything! Including sex and work. I’m professionally chilling

does anyone know any information relating to how much pregnenolone an adult male endogenously secretes daily? Also is it in a diurnal fashion?

on another note but not to change the course of the thread, I was with a buddy last night at a bar and he is like 6’ 180 at 7% bodyfat. He has been on 200mg test e and 200mg tren e for 5 years straight! He looks like a cartoon. And the aggression he has socially is insane. Too bad it will be short lived for him and he doesn’t notice or care.

That guys body is probably irreparably damaged. This blows my mind. Has he ever gotten bloodwork?