T Nation

Pregnenolone


#1

Hi, you guys usually know more about hormones than doctors so looking for some advise... Wondering if anyone has tried pregnenolone hormone by Life flo. I need some reassurance. I have PMDD and took HRT for 8 years, but had to come off it because i have bad IBS/food intolerances. So i've been doing a food intolerance diet for 6 months and finally finished it. PMDD has meanwhile become more severe than before i went on the HRT. So I was desperate and ordered pregnenolone and DHEA off internet.

The DHEA will take a month to arrive so taking pregnenolone just until it arrives. My gyno said it was safe to take DHEA 25mg. But i dont know much about pregnenolone except what i read. I took it for first time today and i'm also taking Flixonase/Flunase nasal spray for my dust mite allergy, and not sure if its safe to take them both together. Advise much appreciated if anyone has experience with this!

Also i had an adrenal stress test and my cortisol was medium in the morning and then dropped low for the rest of the day, lower than reference range according to the lab! :frowning:

I took the pregnenolone for 2 days but was while i had pms and i got very upset again this month and so stopped it because wasn't sure if it was making me more stressed? It can convert to cortisol?


#2

There is essentially no conversion of oral pregnenolone to cortisol, estradiol, or testosterone. Meaningful conversion in the body occurs only at the site of production, where levels of both the conversion enzyme and pregnenolone are high, far higher than what will be achieved with supplementation. It works as pregnenolone, not by converting to these other things. Some of it will metabolize to pregnenolone sulfate, and possibly to some derivatives that favorably affect mood in the brain. But not to anything causing a problem.

It’s a very safe supplement.


#3

Sorry i didn’t make it clear, it’s pregnenolone cream that i’m taking, not oral.

What does it convert to?
Thanks


#4

What are the benefits of pregnenolone? Will it help my mood at all?


#5

I took a product called Orange P7 years ago which made me feel good but they no longer make it.


#6

Pregnenolone is anti-depressive for some, so depending on your mood, it’s possible.

The significant conversion is to pregnenolone sulfate. This is simply part of how pregnenolone works, rather than being a matter of something new to be concerned with.

There is no significant conversion to progesterone, estradiol, testosterone, cortisol, etc.

There can be conversion to 7-hydroxypregnenolone, which is neuroprotective, but whether this amount is significant from oral or transdermal use isn’t known.


#7

Thanks. So what does pregnenolone do then? If it doesnt convert into other hormones. Where is the site that that usually takes place at? :S


#8

Pregnenolone works in the brain towards blocking the actions of allopregnanolone, a neurosteroid which has depressive effect. This is probably the main mode of action of oral or topical pregnenolone.

In the brain, pregnenolone sulfate (but not pregnenolone itself, unless it’s enzymatically converted to the sulfate) modulates the GABA and NMDA receptors as well.

So, normal blood levels of pregnenolone support the normal functions of these receptors.


#9

Ah thats interesting since allopregnenolone is implicated in PMDD. Although i thought i needed more allo as i thought allo acted like valium on the brain? See quote below.

I also need more serotonin, would you recommend taking L-tryptophan over antidepressants? Or anything else like SAMe? I have some tryptophan but haven’t taken it many times yet because i’ve been on the food intolerance diet. I’m also scared to take these supplements everyday.

"During the luteal phase, PMDD women had significantly greater allopregnanolone levels, coupled with significantly lower cortisol levels, during both baseline and mental stress. Moreover, significantly more controls (83%) showed the expected stress-induced increases in allopregnanolone compared with PMDD women (42%). Premenstrual dysphoric disorder women also exhibited a significantly greater allopregnanolone/progesterone ratio than control subjects, suggesting alterations in the metabolic pathways involved in the conversion of progesterone to allopregnanolone.

Finally, PMDD women with greater levels of premenstrual anxiety and irritability had significantly reduced allopregnanolone levels in the luteal phase relative to less symptomatic PMDD women. No relationship between symptom severity and allopregnanolone was observed in controls."


#10

I took some again yesterday, at about 4pm. But dont think i like it, it makes me feel weird and i couldn’t sleep coz took it too late in the day probably.

My pharm grade oral DHEA has arrived. I guess that one does convert to hormones? I kind of want it too as my hormone levels are all low and gyno said i could take it. :slight_smile:


#11

The finding you cite could be a matter of association rather than causation, but in any case is an illustration that it’s also possible for allopregnanlone levels to be lower than normal. In that case, it makes sense that pregnenolone’s action there wouldn’t be helpful.

The more important thing is how it makes you feel. It’s use has no measured health benefit such as reducing cardiovascular risk, etc… the only reason to use would be if you feel better. Since you didn’t, then it sounds like it may not be for you, though a single trial of course isn’t conclusive.

DHEA does have significant conversion to testosterone and estradiol. As you’ve had your blood levels checked and your gynecologist approves, that sounds suitable.

Trimethylglycine, often sold as betaine, often works well for depression. It works similarly to SAMe as a methyl donor, but is much less expensive. Example usage is 2 g/day.


#12

Thanks very much for your help.

Should DHEA and and pregnenolone be taken in the morning or what time of day? Maybe i’ve been taking it too late in the day since it’s disturbed my sleep…


#13

As it happens, I don’t have any information on preferred time of day for taking these; it would have to be by trial and error.


#14

[quote]Bill Roberts wrote:
The finding you cite could be a matter of association rather than causation, but in any case is an illustration that it’s also possible for allopregnanlone levels to be lower than normal. In that case, it makes sense that pregnenolone’s action there wouldn’t be helpful.

The more important thing is how it makes you feel. It’s use has no measured health benefit such as reducing cardiovascular risk, etc… the only reason to use would be if you feel better. Since you didn’t, then it sounds like it may not be for you, though a single trial of course isn’t conclusive.

DHEA does have significant conversion to testosterone and estradiol. As you’ve had your blood levels checked and your gynecologist approves, that sounds suitable.

Bill, I thought I read that pregnenolone provides material to make DHEA in the body. If someone tests low in both would you just supplement with both? Or try each separately first to see how you feel? Is there even a point to supplementing it if your levels are low or is it just a natural part of aging?

Trimethylglycine, often sold as betaine, often works well for depression. It works similarly to SAMe as a methyl donor, but is much less expensive. Example usage is 2 g/day.
[/quote]


#15

It’s true that pregnenolone can become DHEA if much of it were exposed to the enzymes that make the conversion, as occurs when pregnenolone is produced in the adrenals, ovaries, or testes. In those instances, pregnenolone is produced in absolute hotspots for the enzymatic conversion.

The rest of the body has little to none of the needed enzymes, so the vast majority of supplemental pregnenolone has no hope of conversion.

Even the pregnenolone happening to reach for example the ovary as an organ wouldn’t be good enough: you would need a good percentage of the oral pregnenolone to get right inside the exact cells where the enzymes are. That’s just not plausible. The body has trillions of other cells which are going to get equal share, so to speak, so the vast majority of the pregnenolone has no hope of conversion.

To my knowledge increase in DHEA, estradiol, or testosterone levels has never been reported from administration of pregnenolone. This would be for the above reason.


#16

Sounds like it wont do any good if it can’t be used by the cells? Just an extra hormone for the liver to process? :frowning:


#17

If “good” is defined as converting to those other hormones, then no. If it’s defined as working as pregnenolone, then it does good things for mood for some, but perhaps not for you.

There is not any liver burden to speak of.


#18

Ok thanks. I must be confusing it with DHEA, someone on a forum was saying DHEA affected their liver which worried me but think they were taking 50mg or above.