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    Terrible Progest-E reaction. NEED to sort it out.

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    • T
      thelion
      last edited by

      The lion (26, male) wishes to take Progest-E due to its clear and obvious benefits for his health issues such as eczema & allergies as well as just for general looksmaxxing.

      However, when the lion consumes (topically or orally) any progesterone formulation, within 12-24 hours he experiences intense gastrointestinal discomfort. Namely, it becomes impossible for the lion to have a bowel movement for the next 48 hours or so as his bowels becomes totally paralyzed. He also becomes bloated in his midsection to the point where bending over at the waist or sitting down becomes uncomfortable, and there is tangible water retention in “rolls” on his abdomen, despite being lean enough to have visible abdominal muscles. It seems like this water retention might be “strangling” the intestines OR the retention is occurring in the intestinal wall itself.

      The lion has a family history of connective tissue disorders, NAFLD, and celiac disease, including a maternal relative with an intolerance to aspirin due to it causing constipation. However, the lion does not experience EDS symptoms if his androgens are kept high. (Though he does still avoid gluten)

      The lion is not overweight. The notion that this is being caused by massive estrogen releases is somewhat hard for him to believe, because he is rather lean. However, he is open to the idea that it could be trapped in a reservoir somewhere in his body. The lion is also open to the idea that this could be a liver issue. (Could it be fatty liver causing an issue with estrogen detox?)

      The lion does not experience these symptoms when using Testosterone, Dihydrotestosterone, low doses of pregnenolone, (such as from pansterone) or low doses of DHEA (likewise). Additionally, the lion does not believe this to be a nutrient deficiency. Particularly, it does not appear responsive to thiamine, B5, magnesium, ascorbic acid, iodine, or selenium; all of which he has attempted in the past.

      The lion has asked this question on twitter in the past without any workable answers. The lion urgently requires assistance so he can get back to managing the small dog’s insolence. The lion would greatly appreciate expedient assistance in this matter.

      Z C 2 Replies Last reply Reply Quote 1
      • Hando-JinH
        Hando-Jin
        last edited by

        Why not just use pregnenolone instead? Progesterone often does not work out for men.

        T 2 Replies Last reply Reply Quote 0
        • T
          thelion @Hando-Jin
          last edited by

          @Hando-Jin

          Pregnenolone doesn’t have the same benefits at doses the lion can tolerate. It feels excitatory and anti-gaba. Once the lion get up to the doses where it’s effective he runs into the same issue as with progesterone, probably due to conversion.

          The lion does not concern himself with worrying about “anti androgenic” effects that other males complain about. These other males never complain of bowel paralysis, leading the lion to believe that this is a different and unrelated issue.

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          • T
            thelion @Hando-Jin
            last edited by

            @Hando-Jin pregnenolone causes the same issue once the lion is up to doses where it’s actually helpful. At low doses it’s too excitatory to be a serviceable replacement.

            This isn’t an “anti androgenic” issue. When the lion sees guys complaining about response to progesterone it is almost always about it being anti-androgenic. The lion does not concern himself with these things. Never anything about gut paralysis. The lion can only assume this is a separate issue.

            Hando-JinH 1 Reply Last reply Reply Quote 0
            • Z
              zorba990 @thelion
              last edited by

              @thelion Progesterone inhibits acetylcholine in the bowel.

              Ref: https://pmc.ncbi.nlm.nih.gov/articles/PMC9150547/#:~:text=Both isoforms of progesterone receptors,elevating NO levels [37].

              "Both isoforms of progesterone receptors (PR), PR-A and PR-B are present in gastric smooth muscle cells suggesting a direct site of action of progesterone [35]. Preincubation of the dispersed smooth muscle cells 10 minutes before the administration of acetylcholine (Ach), inhibited the induced contraction by acetylcholine. Moreover, progesterone preincubation inhibited Ach-induced Rho kinase II activity without affecting its expression level suggesting that progesterone acts rapidly and directly of gastric smooth muscle cells to inhibit the contractile activity [34]. The same group showed that the effect of progesterone on Ach-induced contraction was achieved by the production of nitric oxide (NO] by progesterone from smooth muscle cells. Nitric oxide in turn induces the formation of cyclic guanosine monophosphate (cGMP) that activates protein kinase A (PKG) that plays a key role in smooth muscle relaxation [35].
              Similarly, Colon smooth muscle contractility was increased in the inflammatory bowel syndrome model induced by water immersion and animal restraint in mice and this change was NO-dependent. Progesterone administrations reversed the increased contractility by elevating NO levels [37]."

              Given this, you may wish to try taking something that will up regulate acetylcholine in the intestines to balance that side effect. If it were me I would try either pantothenic acid or pantethine forms of vitamin B5 and do so somewhat away from taking the dose of progesterone (like hours?). I see that you tried B5 before so perhaps the dose was not large enough? Could try Pantethine maybe at like 600mg or higher? Otherwise there are other things that can up regulate acetylcholine like ALCAR or Alpha-GPC

              Ref: https://www.sciencedirect.com/science/article/abs/pii/S2210522012000068
              "Pantethine is known to increase gastrointestinal motility and improve ileal function [1]. The contractile mechanism is thought to be partially mediated by acetylcholine release from the cholinergic nerve endings [2]."

              As an anecdote I used to use 250mg Calcium Pantothenate for adrenal exhaustion but had to stick to using it sublingually (takes an awful long time for that tablet to dissolve lol) because of the bowel contractions it caused.

              A co-factor for B5 may be Phosphatidyl Choline such that one uses up the other and may be needed for making acetylcholine endogenously.

              Any headaches and I would back off of this though... excessive acetylcholine isn't much fun either.

              1 Reply Last reply Reply Quote 1
              • C
                CrumblingCookie @thelion
                last edited by CrumblingCookie

                What @zorba990 wrote.

                Possibly hand that panethine also to your relative perhaps you share common SMVT phenotypes.

                @thelion said in Terrible Progest-E reaction. NEED to sort it out.:

                NAFLD, and celiac disease, including a maternal relative with an intolerance to aspirin due to it causing constipation.

                @zorba990 How do you feel excess acetylcholine? Swelling of mucosa and a runny nose with overall increased peripheral circulation and warmth and feeling whiny? Calcium-pantothenate dissolves really quickly btw so you could use the contents of capsules instead of solid tablets.

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                • sunsunsunS
                  sunsunsun
                  last edited by

                  This post is deleted!
                  1 Reply Last reply Reply Quote 0
                  • MossyM
                    Mossy
                    last edited by

                    I am not scientifically savvy enough to provide any other description than that I get constipation-like symptoms as well from progesterone, and the mucosa issues, but manifested in dryness of the nasal passages, not runny nose. Maybe it is intermittent — runny, then dry; but I forget exactly. It's been years since I've taken progesterone. All in all, I get what has chronically been an issue in my life — what I'd call dryness related symptoms.

                    "To desire action is to desire limitation" — G. K. Chesterton
                    "The true step of health and improvement is slow." — Novalis

                    C 1 Reply Last reply Reply Quote 0
                    • LukeL
                      Luke
                      last edited by Luke

                      At which doses does The lion experience this? Even small doses topically? Has The lion tried any methods of inducing a bowel movement (like high dose magnesium or carrot salad) when these symptoms happen and even that doesn't work?

                      I've never been a big party attender, but I never went to a party where I didn't probably offend most of the people there by talking about what I was interested in. (Ray Peat)

                      1 Reply Last reply Reply Quote 0
                      • Hando-JinH
                        Hando-Jin @thelion
                        last edited by

                        @thelion Word.

                        Have you tried other formulations of progesterone, like Idealabs progestene or whatever it's called?

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                        • C
                          CrumblingCookie @Mossy
                          last edited by CrumblingCookie

                          @Mossy
                          In the mentioned context of Acetylcholine that overall dryness of yours could be a sign of generally low ACh levels.
                          If you're up for an adventure you could hypothetically seek an anesthesiologist to i.v. inject you with ACh in order to feel and observe your bodily reactions to elevated levels of it. As such a vague diagnostic approach publically doesn't really count as a valid reason I doubt anyone's up to do that "just for fun", though.

                          MossyM 1 Reply Last reply Reply Quote 0
                          • H
                            heyman
                            last edited by

                            The lion says rawr

                            1 Reply Last reply Reply Quote 0
                            • P
                              Peatful
                              last edited by

                              Nothing to add here that is earth shattering:

                              But
                              Think of progesterone as pro-gestation
                              With that
                              Constipation is very common- a big issue during pregnancy for many women

                              Simply lay off

                              You could try upping your carbs or even kcal to see if you tolerate it better
                              But that takes intentionality and time

                              The further society drifts from the truth the more it will hate those who speak it.

                              SD

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                              • MauritioM
                                Mauritio
                                last edited by

                                It might have to with bile acids and the gallbladder.

                                There is a progesterone metabolite that modulates the bile metabolism in such a way that it can cause cholestasis symptoms, constipation is one of them.
                                IIRC it had to with the bile acid receptor FXR.

                                You could try increasing your fiber intake via carrots, bamboo shoots or oat bran.
                                You could also try adding a bit of olive oil to your diet since the fatty acids in it have a tendency to cause a stronger bile release than coconut oil.
                                Another option would be trying FXR agonists like bile acids, androsterone, cafestol, ...

                                Dare to think.

                                My X:
                                x.com/Metabolicmonstr

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                                • MossyM
                                  Mossy @CrumblingCookie
                                  last edited by

                                  @CrumblingCookie
                                  Thank you for the information. It was interesting to read of ACh being a possible factor. My first thought was to attempt to get this with food; or as @zorba990 mentions, pantothenic acid or pantethine forms of vitamin B5. But, the last 15 years has all but put me off of all supplements. I simply can't take them without adverse effects. So, for now, this ACh experiment will have to wait. Though I will make note of it.

                                  "To desire action is to desire limitation" — G. K. Chesterton
                                  "The true step of health and improvement is slow." — Novalis

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