<![CDATA[Trying this again: Progesterone/Pregnenolone - gut paralysis]]>Giving this another shot. Really would like ideally to brainstorm some ideas as to why this might be occurring.

(gross warning)
Basically, any dose and any MOA of progesterone or pregnenolone causes me gut paralysis, to such an extent to where I can feel solid food just sitting in there not moving. And it does seem to stimulate bile release to some extent which would be great if things kept moving but they do not so it's a bit uncomfortable.

This is unfortunate because I am on TRT (medically necessary) and using hCG for neurosteroids/upstream quite frankly sucks balls.

Also worth noting that I've had no such reaction to DHT, Proviron, Anavar, DHEA, 7-KETO-DHEA, testosterone itself, or any steroid that isn't progesterone or a precursor. I do react poorly to oral aspirin (yes I've tried glycine) but my understanding is that's fairly common?

Also worth mentioning I have celiac disease so my gut lining is not super ideal, though I would say in general apart from this I have good digestion so long as I avoid gluten.

I have three competing (complimentary?) theories:

A.) Liver is dumping estrogen and it's causing swelling/water retention in my intestines because it's not properly bound -> then is reabsorbed. Possibly gut bacteria that are cleaving a glucuronic acid off of estradiol glucuronide?

Counterpoint: using estrogen antagonists or aromatase inhibitors alongside progesterone doesn't seem to prevent this.

B.) some kind of vagus nerve or autonomic dysfunction that's worsened by progesterone's anticholinergic effect? Other anticholinergics (diamant. cyproheptadine) also slow my motility somewhat - which is expected - but not the same degree. When this effect kicks in it definitely feels like there's a nervous system dysfunction in the sense that I can't really even "push" effectively.

C.) Similar to both above, but possibly a compound effect from some kind of gut paralyzing SIBO or LIBO (H2S?) - but I don't really have any other symptoms that would suggest this.

Things I have tried:

  • Doxycycline - no effect

  • Clindamycin - no effect

  • BPC-157 injection - temporary relief in time immediately post-injection (no clue as to how this could be working mechanistically)

  • Aromatase inhibitors/anti-estrogens - no effect, joint pain.

  • Cascara - limited effect, not a full solution by any stretch, also disgusting.

  • Magnesium/osmotic laxatives/castor oil/betaine - no effect and worsens discomfort

  • high doses of sodium - extremely mild effect MAYBE once a day if I do it first thing in the morning

  • caffeine/thyroid - no effect

  • thiamine, b5, b6, b2 - no effect. I've really tried with the thiamine owing to the autonomic dysfunction theory but unless I need to be doing 2grams/day for an extended period I'm not sure it's really doing much.

Ideas? Thoughts? This shit is driving me crazy. No pun intended.

]]>https://bioenergetic.forum/topic/9417/trying-this-again-progesterone-pregnenolone-gut-paralysisRSS for NodeWed, 17 Jun 2026 19:26:58 GMTWed, 17 Jun 2026 15:58:07 GMT60<![CDATA[Reply to Trying this again: Progesterone/Pregnenolone - gut paralysis on Wed, 17 Jun 2026 16:53:15 GMT]]>@sunsunsun have you used it for this purpose?

]]>https://bioenergetic.forum/post/65059https://bioenergetic.forum/post/65059Wed, 17 Jun 2026 16:53:15 GMT<![CDATA[Reply to Trying this again: Progesterone/Pregnenolone - gut paralysis on Wed, 17 Jun 2026 16:51:12 GMT]]>@alfredoolivas Nicotine doesn't work I'm using it anyway unfortunately. I'm put off from osmotic laxatives generally they don't work much but I haven't tried sulfate.

@CrumblingCookie I'll bite as you seem to know what you're talking about.

@CrumblingCookie said:

Is this neurosteroid connection in any way any tangible issue or merely vague and wild RPF-induced conjecture? The latter appears not unlikely given also the outright destructively naive antibiotics regimens. Wth

The reason I want neurosteroids is because I am on medically necessary TRT (I have secondary/pituitary hypogonadism, my balls work) - If I don't take HCG I become anhedonic despite high doses of test/DHT - prog/preg rapidly relieve this condition I assume by becoming allopregnanolone or something similar. 3a-DHP as well though that has the same problem I assume by converting back into progesterone/5a-DHP (I think this is possible)

I don't disagree that the antibiotics were dumb, looking back it had no positive effect apart from clearing some eczema, and no effect on my gut whatsoever.

@CrumblingCookie said:

B12 and B6 and folate would be the missing basics for nerves.

I take methylfolate for MTHFR. It definitely has a positive effect. I could probably stand to get more B6 & B12, but truthfully I'm at the stage where it's hard to believe B vitamins are the bottleneck.

@CrumblingCookie said:

It's called gastroparesis and dysmotility. Gastric emptying is cholinergic.
GABA and alpha-GPC. Stimulators of ICC interstitial cells of Cajal, specifically stimulators of CaCC calcium-activated chloride channels and CFTR as e.g. quercetin or kaempferol.
There are authorized pharmaceutical peristalsis inducers as well via the serotonin pathways and of course simply the antidopaminergic anti-emetics.

Are these recommendations? Supplemental choline has not seemed to help much, though I haven't tried alpha-GPC specifically. Nicotine generally does help my motility but when I introduce prog/preg it seems cancelled out.

@CrumblingCookie said:

Does this not point to cortisol as the sole and only remaining other suspect?

Is it possible I'm high cortisol though I have no symptoms that would suggest it? I don't have a puffy face, I don't gain fat in areas which would suggest it, nor am I overweight. I eat a very high carbohydrate diet.

]]>https://bioenergetic.forum/post/65058https://bioenergetic.forum/post/65058Wed, 17 Jun 2026 16:51:12 GMT<![CDATA[Reply to Trying this again: Progesterone/Pregnenolone - gut paralysis on Wed, 17 Jun 2026 16:40:49 GMT]]>Nicotine (unfortunately) with coffee (decaff or caff) & magnesium sulfate (10g) is a temporary fix.

]]>https://bioenergetic.forum/post/65057https://bioenergetic.forum/post/65057Wed, 17 Jun 2026 16:40:49 GMT<![CDATA[Reply to Trying this again: Progesterone/Pregnenolone - gut paralysis on Wed, 17 Jun 2026 16:36:21 GMT]]>@CrumblingCookie naltrexone can also clear the gut out

]]>https://bioenergetic.forum/post/65056https://bioenergetic.forum/post/65056Wed, 17 Jun 2026 16:36:21 GMT<![CDATA[Reply to Trying this again: Progesterone/Pregnenolone - gut paralysis on Wed, 17 Jun 2026 16:16:37 GMT]]>

worth noting that I've had no such reaction to DHT, Proviron, Anavar, DHEA, 7-KETO-DHEA, testosterone itself, or any steroid that isn't progesterone or a precursor.

Does this not point to cortisol as the sole and only remaining other suspect?

causing swelling/water retention in my intestines

That would be intestinal "pseudo-obstruction".

B.) some kind of vagus nerve or autonomic dysfunction that's worsened by progesterone's anticholinergic effect?

It's called gastroparesis and dysmotility. Gastric emptying is cholinergic.
GABA and alpha-GPC. Stimulators of ICC interstitial cells of Cajal, specifically stimulators of CaCC calcium-activated chloride channels and CFTR as e.g. quercetin or kaempferol.
There are authorized pharmaceutical peristalsis inducers as well via the serotonin pathways and of course simply the antidopaminergic anti-emetics.

thiamine, b5, b6, b2 - no effect

B12 and B6 and folate would be the missing basics for nerves.

Wth are you even trying to push prog and preg in the first place?

using hCG for neurosteroids/upstream quite frankly sucks balls.

Is this neurosteroid connection in any way any tangible issue or merely vague and wild RPF-induced conjecture? The latter appears not unlikely given also the outright destructively naive antibiotics regimens. Wth

]]>https://bioenergetic.forum/post/65055https://bioenergetic.forum/post/65055Wed, 17 Jun 2026 16:16:37 GMT<![CDATA[Reply to Trying this again: Progesterone/Pregnenolone - gut paralysis on Wed, 17 Jun 2026 16:01:27 GMT]]>I should also mention that this is a reproducible effect that occurs every time I try prog/preg. Generally, once I get over it I'll wait a few months and work on my digestion and once it's in a good place I'll give it another try and then invariably none of my efforts have made a difference. Probably 4-5 cycles of this at this point.

]]>https://bioenergetic.forum/post/65054https://bioenergetic.forum/post/65054Wed, 17 Jun 2026 16:01:27 GMT