Wooo's "Progesterone, The Master Hormone Myth"

[lollipop]

Yes your are correct lisa. He says that supplying progesterone to the body results in a positive feedback loop. Progesterone encourages the body to produce more progesterone.

Peat advocates the use of progesterone in inflammatory conditions. Alternative health love their omega-3s and unsaturated oils for the very same reason. I often wonder how the industry would cope without the immunosuppressive actions of omega-3 fish oils. Inflammation is the driver of all diseases. So stopping inflammation takes care of many conditions, regardless of their deleterious actions. The push for omega-3s has ramped up after positive results seen in the Alzeihemer's trials.

Orthordox medicine use corticosteriodal meds but know that these have undesirable outcomes and also look to omega-3 oils to suppress inflammation.

We have been taught that inflammation is the body's call for arms to fight invaders or to repair injury. However, there can be much collateral damage in an aggressive immune response.

We have certain immune privileged sites in the body along with the pregnancy state, where an inflammatory immune response would be catastrophic to the organism. In pregnancy, it is the abortion of the fetus.

Other sites are cornea, testes and placenta. Yes, we use to think this was the case in the brain but recent research has shown this is not correct. Immune privilege enables the successful transplant of foreign cornea without high rate of rejection. There is no need to find a compatible donor. An immune inflammatory response would result in scarring and loss of cells that are not replaced beyond the epithelial layer, thus loss of function/sight.

Immune privilege - Wikipedia
So using progesterone, gelatin etc., are more benign than the alternatives. Inflammation drives tumour progression and suppression of inflammation would be a beneficial strategy.

Peat often refers to tissue regeneration without scarring in fetus and new newborn. A time when the immune system has not yet developed.

So the aim is to prevent loss of function and this is only possible if cells develops tolerance to the pathogen and not over react. This means we have to stop thinking about being at war with these pathogens and allow them residency???

A sufficiently energised cell with plenty of thyroid hormone, stabilising factors, oxidising glucose, perhaps does not permit residency. Weakened, starving cells, inflammation attract viruses and pathogens in the same manner microbes attack decaying and decomposing compost heap - they are part of the clean-up crew.

Gershom Zajicek, proposes that cell + virus are the basic unit. If the cell harbours a benefical virus (plant virus) then pathogenic viruses are not permitted.

So basically as I understand it, Peat is saying that healing takes place in the absence of inflammation and when allowed to heal in this manner, prevents the loss of function compared to permitting inflammation and risking scar tissue, thus loss of function.

All of Peat's recommendations focus on the reduction of inflammation and increasing tolerance to antigens.

Peat recalls progesterone applied by syringe into the knees of a gentleman. This man was able to go years (can't remember how many) without aching knees. Progesterone was only applied to facilitate the repair. This man did not continue progesterone after the initial application.

Helpful post @Ella - thanks for taking the time.

 

[haidut]

@haidut

I'm sorry, but you have not provided any kind of proof that progesterone's immunossuppressive actions are false. First, do you know what an immunosuppressant is? Perhaps you have some confusion there? - I am saying this with kindness-. It goes way beyond TLR4 inhibition. As an example, these are just two properties: 1) Progesterone blocks/interferes with the induction of key antimicrobial T helper cells and 2) Progesterone is a powerful inducer of T regulatory cells (a.k.a "Suppressor T cells" -this name says it all, these cells act to suppress immune responses.-). If you can't prove that properties such as 1), 2), etc.., are false, then you are not giving any reason not to call progesterone a immunosuppressant. Until then, yes, progesterone is a immunosuppressant. Fact.



I thought this would be a good proof to be considered (the rest of your post has no relevancy and you don't offer any proof). I have no bias. But I read the study, and this study is done on ***Ovariectomized mice***. This study then tries to simulate how the physiological levels of progesterone and/or estradiol would affect the response to viral challenge. Haidut, this is not any sort of "proof" that progesterone is not a immunosuppressant. It quite shows the opposite....

"Estradiol treatment prior to immunization caused the vaginal epithelium to become resistant to TK− HSV-2. " and "the attenuated virus caused a productive infection in progesterone-treated and saline control groups; protection from viral challenge was observed in these mice 3 weeks later. This outcome correlates with previous results from our studies, where E2-treated mice were resistant to primary genital infection with wild-type HSV-2, whereas non-hormone-treated and progesterone-treated groups were highly susceptible"​

In fact your study acts to contradict what you're claiming, because they found out that progesterone without estrogen made the mice "highly susceptible" to herpes. What they call "protective" is in reference to the immunization they are trying to study. In other words, the immunization is useless without progesterone (assuming normal estrogen status) since the herpes virus can't infect the cell to begin with; conversely, progesterone treated ones allow the virus to infect the cell (i.e progesterone induces susceptibility): thus the infection takes place and the immunization can work according to authors.

I choose to think that you indeed read the study and somehow missed all those details, didn't understand the study, or you just read the abstract. I don't believe you're being intentionally dishonest.


Haidut, I have personally NOT called progesterone as an equal to cortisol/estrogen. You've misrepresented me. Please, to make our exchange more clear and honest, stick to what I have said/not said. I in fact mentioned that progesterone has some very interesting caveats that may, in my opinion -and experience-, make it a much better/safer/benign immunosuppresant than say corticosteroids (we absolutely agree here).


If you read the thread from the beginning, you'll see the point of the discussion is to learn about the effects of progesterone on the immune system, with a special interest in its immunosuppressive effects. At least the original poster @Hitoshi seemed to be willing to exchange information on that, as I was.

How is getting informed on the different immunological effects of progesterone (mind you, REAL progesterone), is raising "fear, uncertainty, and doubt"? Perhaps the real fear should come when a person uses a hormone or other supplement without having a decent picture of its relevant pharmacological profile on the bodily systems, about dosages, interactions, and side effects, and then getting problems from a lack of understanding.

I would SO appreciate you tried to add to the conversation instead of avoiding it with accusing people who want to get informed and educated to be "fear mongerers", all the meanwhile not offering any kind of proof that progesterone immunosuppresive effects are false research (again, I'm sticking to natural progesterone).
And yes, if a person using progesterone uses enough of it to cause it to exert powerful immunosuppression such that key antimicrobial immune cells/functions are suppressed enough, yes, they are probably going to be more susceptible to infection and/or worse outcomes. But it's not on me to make people believe that, I am not trying to "convince" anyone, as you accuse me.


We agree on this. Let's not throw progesterone and progestins together. I never have, so why do you bring this up? Your whole paragraph about progestins is not called for, I never lump them together, you're rebutting something I haven't even said.


Direct antiviral effects of progesterone is not directly relevant to the main discussion here, i.e progesterone immunosuppressive actions. That's not a proof of falsity of progesterone's immunosuppressive actions. Almost totally irrelevant to the discussion. In fact, you can readily find other studies showing that natural progesterone increases viral replication Effects of Female Sex Hormones on Susceptibility to HSV-2 in Vaginal Cells Grown in Air-Liquid Interface
.

"Cells grown under ALI conditions were exposed to HSV-2-green fluorescent protein (GFP) and the highest infection and replication was observed in the presence of P4."
"...under these conditions P4 was found to confer higher susceptibility to HSV-2 infection in vaginal cells."
"HSV-2/GFP Infection in Vk2 Cells Cultured in Progesterone [P4] Is Higher Than in Estradiol"
"Progesterone Increases Viral Replication in Vk2 Cells in Both ALI and LLI Cultures"
"...shedding was higher in both P4 and MPA under LLI conditions, P4 showed significantly higher viral replication in ALI cultures."
"suggest that P4 levels can play a significant role in altering the female’s susceptibility to STIs. Although the mechanism of enhanced viral replication in P4-treated cultures is not clear, ALI conditions could trigger changes such as enhanced HSV-2 receptor expression or downregulation of certain antiviral innate responses."​

(Note: Irrelevant to the discussion, but isn't it interesting that Natural Progesterone led to worse outcomes than the progestin MPA and than Estradiol? I'm mentioning since you brought progestins and estrogen to the table. But I maintain, this is just a side note. Also, there are studies showing some anti-viral effects of corticosteroids, and such findings don't negate the fact that corticorsteroids can exert imunosuppression.)


The study of yours that I considered at first goes on to show that even physiological levels of progesterone goes on to give high susceptibility to viral colonization. But of course, I wouldn't use that study to prove what I have tried to focus on, that is, supra physiological levels of progesterone being a immunosuppressant. But if even progesterone at physiological doses made the animals "highly susceptible" ("progesterone-treated groups were highly susceptible"), I can't but wonder if supra physiological would make more than highly susceptible. Probably so, not only from this study, but from all the already known immunosuppressive effects progesterone can exert.

Anyone interested in learning about the immunological effects of progesterone (natural one, "P4") can find info on science databases. I can also share some of the information that I have so far if you ask me to (so far no one has asked).

Finally, not relevant to the main discussion, but since you mentioned that TLR4 inhibition can dampen "inappropriate" immune/inflammation responses, I'll share with you that administration of immunosuppressants/TLR4 antagonists to sepsis patients not only has *not* improved the outcomes, but has also INCREASED mortality in the clinics. Actually, many researchers are calling for the use of immune-enhancing (i.e pro-inflammatory) agents, including "TLR4 agonists" at strategic points in time. Since progesterone is a TLR4 antagonist, that should make one pause before using it mindlessly in case of facing infection. These decisions are person, pathogen, and circumstance-dependent. One supporting paper here: Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach

I'm sorry if sharing information on the immune actions of progesterone induces fear/FUD -as you call it- in you @haidut or in anyone else. I wasn't aware that could be the case. I personally think by learning, people who deal with complex health problems can make better decisions. In truth there's freedom. One of my main areas of interest is the immune system/infectious diseases (as a person who has suffered from such problems herself), so I probably don't have much to contribute to the forum anymore if there's fear/disdain/censorship/mockery to learn a more complete picture about it, specially in regards to supplement effects.

I hope the best for everybody.

I think there may be indeed a confusion of definitions. Here is the definition I use.
Immunosuppression - Wikipedia
"...Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions."

So, under that definition cortisol actually does both - i.e. reduction in both the activation AND efficacy of the immune system. Progesterone does at most a reduction in the activation but not the efficacy. Perhaps just as importantly, progesterone is NOT in the list of officially recognized immunosuppressive drugs. Forgive me for quoting Wikipedia, but it is the reflection of currently established medical practice. When you go to your doctor with an autoimmune flare up he/she does not give you a progesterone shot, you get a cortisone shot. When you have an organ transplant you do not get a progesterone shot for the rest of your life, you get a cortisone shot (and other poisons). When you go to the hospital with sepsis you do not get a progesterone shot, again you get a cortisone shot. Like you said, getting a progesterone shot would be preferable in many of these cases, but current medicine does not consider progesterone in the same class of immunosuppressive agents as cortisone and and the synthetic glucocorticoids.
Immunosuppressive drug - Wikipedia

When you call something immunosuppressive, most people here do not bring up mental images of inducing T regulatory cells. They think of something that represses their ability to fight infection or increases chances of establishing new one, or being used in one of the scenarios I mentioned above - autoimmune "treatment", organ transplant rejection, sepsis treatment, etc.
Btw, if you accept the "morphostasis" theory of immunity then progesterone is clearly NOT immunosuppressive - under no circumstances does it inhibit/reduce cellular integrity, quite the opposite actually. Cortisol and estrogen do the exact opposite and thus are truly immunosuppressive both under current theory and under more recent ones like the morphostasis one.
My comments were not directed strictly at you but towards the general idea of this thread - i.e. somehow lumping progesterone together with other officially labelled immunosuppressive steroids and raising concerns about its use, when nobody in clinical practice views this steroid as such. That does not mean we should take the mainstream view as the truth, as we rarely do here. But the term immunosupressive has a very specific connotation in clinical practice and progesterone does not fit into that meaning. That is what I don't get about this thread - what is the overall goal?? To convey a sense of uncertainty about progesterone by using a term most people associate with very negative events? Again, not just you involved here but the original blog post on which this thread is based and some of the comments in this thread are hard to not see as having this effect (if not purpose) - i.e. raising concerns, doubts and uncertainties about progesterone and its use. Yes, progesterone should be used carefully like all other steroids and your doctor should be consulted. But if you have specific recommendations or concerns about usage, dosage, contraindication, etc then it's best to state them. Having a thread that simply raises doubt by using a term with very specific (and largely negative) meaning while providing very little actionable information is pointless. Again, not a criticism directed specifically at you.

TLDR: Progesterone is currently NOT on the list of officially recognized immunosuppressive drugs. While it does have ability to inhibit specific immune subsystem activation it is not a classic immunosuppresant like cortisol, so a better term would probably be a "SIRM" - selective immune response modulator (yes I know this term does not exist). Under the morphostatis theory of immunity progesterone is never " immunosuppressive" (assuming this term even makes sense under that theory) while cortisol and estrogen are immunosuppressive under both theories. Calling progesterone immunosuppressive and raising vague doubts about its role in viral infections (where the evidence is mixed) is neither actionable nor beneficial (IMO). Again, if we have specific information about doses, conditions, and contraindications then this is probably what we should be discussing. The purpose of the original blog post on which this thread is based and some of the comments in this thread achieve very little along those productive lines and are hard not to see as FUD. But that could be just me seeing things that are not there. And again, my rant is not directed at your specifically :)

 

[Such_Saturation]

It's like when they say salt "raised blood pressure" in people who had it low. What the hell? Just by talking along the axis of "immunosuppression" and "immune boosting" you are leaving Ray Peat's view of the organism. You aren't furthering the discussion. You're just using our megabytes.

 

[PakPik]

I think there may be indeed a confusion of definitions. Here is the definition I use.
Immunosuppression - Wikipedia
"...Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions."

So, under that definition cortisol actually does both - i.e. reduction in both the activation AND efficacy of the immune system. Progesterone does at most a reduction in the activation but not the efficacy. Perhaps just as importantly, progesterone is NOT in the list of officially recognized immunosuppressive drugs. Forgive me for quoting Wikipedia, but it is the reflection of currently established medical practice. When you go to your doctor with an autoimmune flare up he/she does not give you a progesterone shot, you get a cortisone shot. When you have an organ transplant you do not get a progesterone shot for the rest of your life, you get a cortison shot (and other poisons). When you go to the hospital with sepsis you do not get a progesterone shot, again you get a cortisone shot. Like you said, getting a progesterone shot would be preferable in many of these cases, but current medicine does not consider progesterone in the same class of immunosuppressive agents as cortisone and and the synthetic glucocorticoids.
Immunosuppressive drug - Wikipedia

When you call something immunosuppressive, most people here do not bring up mental images of inducing T regulatory cells. They think of something that represses their ability to fight infection or increases chances of establishing new one, or being used in one of the scenarios I mentioned above - autoimmune "treatment", organ transplant rejection, sepsis treatment, etc.
My comments were not directed strictly at you but towards the general idea of this thread - i.e. somehow lumping progesterone with other officially labelled immunosuppressive steroids and raising concerns about its use, when nobody in clinical practice views this steroid as such. That does not mean we should take the mainstream view as the truth, as we rarely do here. But the term immunosupressive has a very specific connotation in clinical practice and progesterone does not fit into that meaning. That is what I don't get about this thread - what is the overall goal?? To convey a sense of uncertainty about progesterone by using a term most people associate with very negative events? Again, not just you involved here but the original blog post on which this thread is based and some of the comments in this thread are hard to not see as having this effect (if not purpose) - i.e. raising concerns, doubts and uncertainties about progesterone and its use. Yes, progesterone should be used carefully like all other steroids and your doctor should be consulted. But if you have specific recommendations or concerns about usage, dosage, contraindication, etc then it's best to state them. Having a thread that simply raises doubt by using a term with very specific (and largely negative) meaning while providing very little actionable information is pointless. Again, not a criticism directed specifically at you.

TLDR: Progesterone is currently NOT on the list of officially recognized immunosuppressive drugs. While it does have ability to inhibit specific immune subsystem activation it is not a classic immunosuppresant like cortisol, so a better term would probably be a "SIRM" - selective immunoregulatory modulator (yes I know this term does not exist). Calling progesterone immunosuppressive and raising vague doubts about its role in viral infections (where the evidence is mixed) is neither actionable nor beneficial (IMO). Again, if we have specific information about doses, conditions, and contraindications then this is probably what we should be discussing. The purpose of the original blog post on which this thread is based and some of the comments in this thread achieve very little along those productive lines and are hard not to see as FUD. But that could be just me seeing things that are not there. And again, my rant is not directed at your specifically :)

@haidut You keep avoiding the points/facts raised on progesterone immunosuppressive effects.

The fact that it is not listed as an immunosuppressant on WikiPedia doesn't automatically prove that it isn't . Or does every immunosuppressant that exists on the Earth have to be listed on WikiPedia, and if it is not listed there, then it isn't one? You're not adding anything to the argument here by mentioning that. You seem to be avoiding the argument haidut, I am sorry to say.​

Your claim: "Progesterone does at most a reduction in the activation but not the efficacy."

You're wrong, it does both things.​

You claim: "When you call something immunosuppressive, most people here do not bring up mental images of inducing T regulatory cells. They think of something that represses their ability to fight infection or increases chances of establishing new one, or being used in one of the scenarios I mentioned above - autoimmune "treatment", organ transplant rejection, sepsis treatment, etc."

And what do you think that a powerful induction of T regulatory cells achieve? It impairs ability to fight infections, lowers the so-called autoimmunity reactions, and increases the chances of establishing newinfections. Have you studied what T-regulatory/T-suppressive cells do? That's exactly some of the things they can do.

With "immunosuppression" the definition of wikipedia is good, and it fits what progesterone can do. If by the word immunosuppression people are lead to think of cyclosporin, well, that's something entirely cultural. Let's stick to the scientific (not cultural) definition of an immunosuppressant, even to the wikipedia one, please: and progesterone fits in it.​

You say: "My comments were not directed strictly at you but towards the general idea of this thread - i.e. somehow lumping progesterone with other officially labelled immunosuppressive steroids and raising concerns about its use"

First of all, I'd recommend that if you have anything to say regarding posts not written by me, do it in a separate message and refer to specific person who said so. Your message was a response to my message and you started mixing in how all of the progestin subject was suspicious, etcetera. Problem is, @haidut, I didn't claim any of that, and I am in agreement with you. So you threw that in what was basically your response to me, a rebuttal to something I didn't even say and something I don't even believe? That my friend, is dishonest, I hope you did it cluelessly/unintentionally.​

In the end you didn't provide any single proof to nullify or show how false the already studied and discovered immunosuppressive actions of progesterone are -which they aren't, but I want to learn about nuances-.​

You say: "To convey a sense of uncertainty about progesterone by using a term most people associate with very negative events?"

Why should we not use the term "immunosuppressive" if it is technically correct? Why the censorship? That's my question. Because some people would get offended, fearful and associate negative things with progesterone? That doesn't make sense. And why do you presume that people such as me want to convey a "sense of uncertainty" by trying to understand more deeply progesterone immunological effect? If anything, by understanding more deeply what progesterone does, there should be a reduction in uncertainty.​

You claim: "Calling progesterone immunosuppressive and raising vague doubts about its role in viral infections (where the evidence is mixed) is neither actionable nor beneficial (IMO)"

Haidut, it has been you who have posted references on studies that backfire on your poor attempts to muddle the conversation (I say muddle because of your complete avoidance of the main points on the table, whilst inserting irrelevancy). It's not my fault you picked those studies, which end up discrediting you. You're the one adding confusion. What could have been much straightforward, insightful, fruitful, clear exchanges, have been muddled post after post by you and other posters who do nothing but block the conversation and add nothing to either agree with it, or disprove it. You're the one introducing confusion and vagueness.​

You claim: "Having a thread that simply raises doubt by using a term with very specific (and largely negative) meaning while providing very little actionable information is pointless."

Once again, the fact that a supplement can have some negative action on some context doesn't mean that I am being "negative" about the supplement.

How can we get to "actionable information" if we aren't even able to discuss the properties of progesterone on the immune system? We haven't even been able to discuss those properties, so that then we could maybe conclude useful/insightful things. If you were so interested to get to convey "actionable steps" we'd be all participating and learning from a conversation on the immunological properties of progesterone, and at the end share the insights. But you and other people have only tried to block and deviate what some of us are trying to learn/share.​

Finally, in the same sentiment: I've seen @tyw present very well constructed and researched arguments and explanations, he offers almost full valid support to what he claims, and when it becomes too evident that he is onto something and you're not providing proof why he is wrong, whilst oftentimes you having a weak/invalid argument, then you resort to the 'but what are the "actionable steps"' to kind of devalue/exit what he has argued or him pointing out your faulty arguments. All the meanwhile many posters start to mock Tyw and said false, demeaning things about him without offering a single true rebuttal to what he posts -seems to me you are all afraid of him-.​

I'm sorry, but this is all wrong and very destructive. Again you're providing nothing but avoidance and irrelevancy. I do hope it is not intentional. I hoped to learn and discuss together.​

I hope the best for you, haidut.​

 

[Regina]

It's like when they say salt "raised blood pressure" in people who had it low. What the hell? Just by talking along the axis of "immunosuppression" and "immune boosting" you are leaving Ray Peat's view of the organism. You aren't furthering the discussion. You're just using our megabytes.

Yea, the parallax view.

 

[Tarmander]

I have really enjoyed this discussion. It has shown me really how different Ray is and how his views meld so poorly with the main medical views. I think we run into a lot of mistakes when we take what he says and put it over the medical ideology we are very used to. I have no doubt that progesterone can lower immunity in a documented, scientific sense. Is that even the right way to say it?

I have a couple latent infections and they prevent me from taking any significant amount of glycine. Glycine makes me feel great and sleep great, but then I get sick! Obviously my body cannot get rid of these long term infections. Glycine makes my body stronger, less inflamed, raises metabolism. But then I get sick, and sick in a very personally concerning way.

Some of this stuff just kind of sucks as a perscription. It doesn't fit his model. I have seen a lot of people on these forums say that a high sugar diets destroy their health. I don't think they are lying. Ray describes youthful metabolism a lot, and it's lack of aging. He describes substances associated with this. So I should be able to take these and get younger right? How is it causing the opposite?

It does though! Youth begets more youth. Aging begets further aging.

 

[Hitoshi]

thankyou @PakPik and @tyw for excellent responses.

@haidut - the aim of the thread is not to cause feelings of uncertainty, but as has been mentioned, to raise awareness, and was written in curiosity, as i was unaware of those effects myself as a practitioner. it was pure interest as to the means why which the body would employ this mechanism.

this forum would be pretty boring if all it contained were affirmations of what most readers clearly think is correct thinking already by Peat. It appears that is exactly what some users are looking to achieve....any time something is called into question, not even for reasons of sowing doubt, the default response is agitation and frustration and even anger...

if one were to look back at the initial post, one owuld see presentation of an article, and the word "discuss"

it seems that is what is unfolding, and this, as @PakPik says, can only lead to higher level sof understanding and confidence

 

[Hitoshi]

It's like when they say salt "raised blood pressure" in people who had it low. What the hell? Just by talking along the axis of "immunosuppression" and "immune boosting" you are leaving Ray Peat's view of the organism. You aren't furthering the discussion. You're just using our megabytes.

i dont think that's the case. It is assumed that Rays ideas underpin all stuff read and written on this forum. At least this is my assumption. The thread fails when someone sees immunosuppression as inherently "bad."
obviously if the body contains these messengers that have these (seemingly bizarre) effects (based on the context of peats writing), it is for the greater good of the organism somehow, and that is what i was hoping to flesh out in this thread.

i dont think just using words like "immunosuppression" goes against the mentality at all. it opens up a discussion as to the evolutionary/survival advantage of this action.

 

[milk_lover]

This is funny. I think progesterone might be the single best supplement that has worked for me. It's up there with K2 and Andro and thyroid and taurine. I enjoyed reading this thread, nonetheless.

 

[whodathunkit]

Like @Tarmander, this thread has clarified some significant points for me, where Peat's views are so very different from mainstream but also why and how they don't necessarily work for everyone. Big difference from being confused as to why such a sensible strategy as Peat's doesn't seem to work for me and understanding that many of the difficulties be stemming from a compromised immune system and immunosuppressive effects of some of his recommendations. Compromised immune system or latent infections are something that can perhaps be addressed or at least compensated for, whereas confusion or lack of knowledge/understanding can only beget discouragement.

My most recent bout of experimentation with progesterone ended with me feeling on the edge of flu for a couple of weeks and finally getting a strong inflammatory response (as evidenced by severity of menses). This recent reactions and all my historical difficulties with progesterone make a lot more sense now in the context of this discussion.

Cortisol has a lot to do with it, too. I'm quite acutely stressed at the moment, and have been for a couple of months now. But it wasn't until I added to progesterone to hopefully take down the stress a few notches that I started feeling immune effects.

 

[haidut]

@haidut You keep avoiding the points/facts raised on progesterone immunosuppressive effects.

The fact that it is not listed as an immunosuppressant on WikiPedia doesn't automatically prove that it isn't . Or does every immunosuppressant that exists on the Earth have to be listed on WikiPedia, and if it is not listed there, then it isn't one? You're not adding anything to the argument here by mentioning that. You seem to be avoiding the argument haidut, I am sorry to say.​

Your claim: "Progesterone does at most a reduction in the activation but not the efficacy."

You're wrong, it does both things.​

You claim: "When you call something immunosuppressive, most people here do not bring up mental images of inducing T regulatory cells. They think of something that represses their ability to fight infection or increases chances of establishing new one, or being used in one of the scenarios I mentioned above - autoimmune "treatment", organ transplant rejection, sepsis treatment, etc."

And what do you think that a powerful induction of T regulatory cells achieve? It impairs ability to fight infections, lowers the so-called autoimmunity reactions, and increases the chances of establishing newinfections. Have you studied what T-regulatory/T-suppressive cells do? That's exactly some of the things they can do.

With "immunosuppression" the definition of wikipedia is good, and it fits what progesterone can do. If by the word immunosuppression people are lead to think of cyclosporin, well, that's something entirely cultural. Let's stick to the scientific (not cultural) definition of an immunosuppressant, even to the wikipedia one, please: and progesterone fits in it.​

You say: "My comments were not directed strictly at you but towards the general idea of this thread - i.e. somehow lumping progesterone with other officially labelled immunosuppressive steroids and raising concerns about its use"

First of all, I'd recommend that if you have anything to say regarding posts not written by me, do it in a separate message and refer to specific person who said so. Your message was a response to my message and you started mixing in how all of the progestin subject was suspicious, etcetera. Problem is, @haidut, I didn't claim any of that, and I am in agreement with you. So you threw that in what was basically your response to me, a rebuttal to something I didn't even say and something I don't even believe? That my friend, is dishonest, I hope you did it cluelessly/unintentionally.​

In the end you didn't provide any single proof to nullify or show how false the already studied and discovered immunosuppressive actions of progesterone are -which they aren't, but I want to learn about nuances-.​

You say: "To convey a sense of uncertainty about progesterone by using a term most people associate with very negative events?"

Why should we not use the term "immunosuppressive" if it is technically correct? Why the censorship? That's my question. Because some people would get offended, fearful and associate negative things with progesterone? That doesn't make sense. And why do you presume that people such as me want to convey a "sense of uncertainty" by trying to understand more deeply progesterone immunological effect? If anything, by understanding more deeply what progesterone does, there should be a reduction in uncertainty.​

You claim: "Calling progesterone immunosuppressive and raising vague doubts about its role in viral infections (where the evidence is mixed) is neither actionable nor beneficial (IMO)"

Haidut, it has been you who have posted references on studies that backfire on your poor attempts to muddle the conversation (I say muddle because of your complete avoidance of the main points on the table). It's not my fault you picked those studies, which end up discrediting you. You're the one adding confusion. What could have been much straightforward, insightful, fruitful, clear exchanges, have been muddled post after post by you and other posters who do nothing but block the conversation and add nothing to either agree with it, or disprove it. You're the one introducing confusion and vagueness one.​

You claim: "Having a thread that simply raises doubt by using a term with very specific (and largely negative) meaning while providing very little actionable information is pointless."

Once again, the fact that a supplement can have some negative action on some context doesn't mean that I am being "negative" about the supplement.

How can we get to "actionable information" if we aren't even able to discuss the properties of progesterone on the immune system? We haven't even been able to discuss those properties, so that then we could maybe conclude useful/insightful things. If you were so interested to get to convey "actionable steps" we'd be all participating and learning from a conversation on the immunological properties of progesterone, and at the end share the insights. But you and other people have only tried to block and deviate what some of us are trying to learn/share.​

Finally, in the same sentiment: I've seen @tyw present very well constructed and researched arguments and explanations, he offers almost full valid support to what he claims, and when it becomes too evident that he is onto something and you're not providing proof why he is wrong, whilst oftentimes you having a weak/invalid argument, then you resort to the 'but what are the "actionable steps"' to kind of devalue/exit what he has argued or him pointing out your faulty arguments. All the meanwhile many posters start to mock Tyw and said false, demeaning things about him without offering a single true rebuttal to what he posts -seems to me you are all afraid of him-.​

I'm sorry, but this is all wrong and very destructive. Again you're providing nothing but avoidance and irrelevancy. I do hope it is not intentional. I hoped to learn and discuss together.​

I hope the best for you, haidut.​

And you seem to be employing the same arguments as in recent threads that basically say - "look, substance X has this property. Prove that it is not harmful!" I think @Drareg was the first to notice this recent trend.
I am not avoiding the argument, I am trying to avoid the name calling for a steroid just because it partially meets your narrow definition of an immunosuppressant. I pointed out that progesterone is not accepted as a clinically relevant immunosuppressant in the categories that cortisol and estrogen are. That is what matters! Its systemic, clinically relevant effects in humans are NOT that of an immunosupressant and that is why it is NOT listed in that category. It may be an immunomodulator but it is NOT an immunosuppressant. And yes, that list of officially sanctioned immunosuppressive drugs is exhaustive because it lists categories of chemicals and not only specific chemicals. Do you see the category glucocorticoids there? I do. Do you see the category progestins there? I do not. Do you want me to get you the list from the FDA or the Merck Manual? It looks pretty much the same and progesterone is not there. So, if you want to play the word game just because progesterone matches some template then be prepared to explain why progesterone is not listed in the category of the other drugs that match the same template.
I tell you what. Let's have another "productive" exercise in name calling. Progesterone is technically an agonist of the androgen receptor, albeit a weak one. Here is a study showing progesterone has anabolic effects similar to testosterone as per the official levator ani test.
https://raypeatforum.com/community/threads/the-anabolic-effects-of-progesterone.16381/

So, technically progesterone is an androgenic, anabolic steroid (AAS). Yay, how constructive name calling that would be, and because we all know how risky AAS can be let's start talking about the potential risks of using progesterone as an AAS. Better yet, hey FDA why don't you ban progesterone because it is an AAS? But progesterone is still here and available OTC precisely because in a clinical setting it does not have the systemic effects of an AAS and the FDA knows that. It seems to have some of AAS effects in specific tissues (brain and prostate come to mind), but for all intents and purposes it is not an AAS. So, starting a thread and discussing progesterone as an AAS is pointless without specific context/condition/organ/tissue.
Once again, the discussions so far in this thread have added nothing specific, nothing experimental/actionable. If you wanted to really discuss progesterone and its immunosuppressive effects it should have started with a study that says "hey, in this condition administering progesterone is detrimental because of its immunosuppressive effects. Here is why and here is where else it could be risky, and maybe it is a dose-response effect, etc" The studies I posted so far showed progesterone to be beneficial for the overall course of the viral conditions, and in some cases it did reduce the viral load but in others it did not. That is what matters! Progesterone is systemically beneficial despite the "immunosuppressive" context being framed in this thread.
But hey, who cares about outcomes. Let's call a steroid a name and talk about T cells instead.

 

[haidut]

thankyou @PakPik and @tyw for excellent responses.

@haidut - the aim of the thread is not to cause feelings of uncertainty, but as has been mentioned, to raise awareness, and was written in curiosity, as i was unaware of those effects myself as a practitioner. it was pure interest as to the means why which the body would employ this mechanism.

this forum would be pretty boring if all it contained were affirmations of what most readers clearly think is correct thinking already by Peat. It appears that is exactly what some users are looking to achieve....any time something is called into question, not even for reasons of sowing doubt, the default response is agitation and frustration and even anger...

if one were to look back at the initial post, one owuld see presentation of an article, and the word "discuss"

it seems that is what is unfolding, and this, as @PakPik says, can only lead to higher level sof understanding and confidence

There is nothing unfolding here other than attempts to attach a pointless definition/name to progesterone, which while technically (only partially) correct, ignores its systemic effects and how the steroid is used clinically. So, sadly and because of this thread, for most people who visit the forum the takeaway message would be "Danger, danger, progesterone is immunosuppressive. Wait, what else is immunosuppressive? Ah yes, cortisol - they said progesterone is GR agonist. So, progesterone is similar then?! Better to avoid". I suppose caution is always advisable, but this thread does not give this caution any concrete meaning/guidance. No talk about conditions, doses, context, etc where progesterone has been shown to be dangerous/unadvisable. Only the vague spooky message of "when there is any doubt there is no doubt".
Same thing unfolded in the thread on Vitamin D as an immunosuppressant, and the thread I posted on carbonic anhydrase inhibition - some people started jumping in and pouring an abundance of extensively theoretical definitions (as opposed to facts) that are completely irrelevant in practice. No actual evidence to the contrary, just statements very similar to the ones in this tread along the lines of "But X belongs to category Y and Y is defined as not good. So, people, don't be so sure about the benefits of X".

Speaking of definitions - can pakpik please show a reference to a definition in a textbook or some other reputable/official source (since we are speaking of definitions) that confirms the following statement of yours:

If a substance complies with both

1) Said substance blocks/interferes with the induction of key antimicrobial T helper cells and 2) Said substance is a powerful inducer of T regulatory cells (a.k.a "Suppressor T cells" -

Then a substance is immunosuppressive.

When pakpik proves that 1) and 2) are the core definitions of an immunosuppressant then she/he can claim progesterone is immunosuppresive. Not because I say so but because pakpik is claiming a change of definition for a given substance (progesterone) which is not currently accepted. Not the other way around - show a substance satisfies a partial definition on something and then ask the other person to prove the substance should not be called with the generic term encompassing so much more than the narrow definition.
If you think the evidence establishes for a fact that progesterone is immunosuppressive then I expect to see everybody on the forum start referring to testosterone as a progestin. You know, because it satisfies partially the requirements for a progestin - i.e. agonism at PR and maintenance (albeit imperfectly) of pregnancy.

If you think the forum benefits from raising doubt without materializing it through health outcomes then fine. I don't. Time for me to move on and remember to not engage in threads unless specifically called upon. I think tyw is spot on right on that.

 

[haidut]

It's like when they say salt "raised blood pressure" in people who had it low. What the hell? Just by talking along the axis of "immunosuppression" and "immune boosting" you are leaving Ray Peat's view of the organism. You aren't furthering the discussion. You're just using our megabytes.

Yep, and even just focusing along the axis of immunosuppression it is clear that progesterone has often opposite effects to cortisol - i.e. progesterone raises core body temp while cortisol lowers it (body temp is crucial for proper immune response), progesterone protects the thymus while cortisol destroys it, progesterone raises the NAD/NADH ratio, while cortisol lowers it, and so on.
But hey, progesterone is immunosuppressive, be very afraid.

 

[milk_lover]

I tell you what. Let's have another "productive" exercise in name calling. Progesterone is technically an agonist of the androgen receptor, albeit a weak one. I will post a study today showing progesterone has anabolic effects similar to testosterone as per the official levator ani test. So, technically progesterone is an androgenic, anabolic steroid (AAS). Yay

This is an amazing find! Can't wait for that post. I bet the dose is low as that I would suspect benefits me the most (I get libido boost too from it)

 

[whodathunkit]

But hey, progesterone is immunosuppressive, be very afraid.

FWIW, as someone who has always and still does have trouble with progesterone, that's definitely not the takeaway I'm getting from this thread at all.

I'm just reading everything and seeking answers.

Can you help me understand why I got the immune suppression effect I did when dosing with progesterone a couple of weeks ago, now that I'm under a lot of chronic stress again? I started the progesterone to mitigate stress but instead it seemed to make it worse. Does this mean that in order for progesterone to be beneficial that most other conditions in the body must be optimal?

 

[haidut]

FWIW, as someone who has always and still does have trouble with progesterone, that's definitely not the takeaway I'm getting from this thread at all.

I'm just reading everything and seeking answers.

Can you help me understand why I got the immune suppression effect I did when dosing with progesterone a couple of weeks ago, now that I'm under a lot of chronic stress again? I started the progesterone to mitigate stress but instead it seemed to make it worse. Does this mean that in order for progesterone to be beneficial that most other conditions in the body must be optimal?

Maybe progesterone raised your core body temp and you got a mild fever? Often the signs of body temp are the opposite of what we think. When you feel cold and feverish body temp is high. When you sweat and feel hot body temp is usually dropping.
You can get the same effects from thyroid hormone (T3) and some other so-called pyrogenic steroids. It does not mean it is suppressing your immune system and you are getting a flu. The fever response is mostly driven by a balance between various steroids with opposing action like progesterone and cortisol/estrogen. Progesterone is a pyrogenic steroid, and cortisol/estrogen are the exact opposite. Another opposition in effects.
Studies on steroid fever. II. Pyrogenic and anti-pyrogenic activity in vitro of some endogenous steroids of man. - PubMed - NCBI
"...Inhibition of pyrogen release from human leukocytes in vitro by hydrocortisone and estradiol was demonstrated. Hydrocortisone-treated leukocytes released less pyrogen than did normal leukocytes when stimulated either by etiocholanolone or by phagocytosis of heat-killed staphylococci. On the other hand, estradiol-treated blood leukocytes and mononuclear cells showed significant suppression of pyrogen release when phagocytosis, but not etiocholanolone, was used as the stimulus. When blood cells were incubated with progesterone, greater than normal amounts of pyrogen were released following phagocytosis, and the inhibiting effect of estradiol could be partially reversed. Neither estradiol nor hydrocortisone appeared to act on rabbit leukocytes. These studies indicate that a variety of naturally-occurring steroids may alter pyrogen release from leukocytes. Alterations in steroid balance in man may influence normal temperature regulation and contribute to clinical fevers."

 

[haidut]

This is an amazing find! Can't wait for that post. I bet the dose is low as that I would suspect benefits me the most (I get libido boost too from it)

Well, here it is if you are interested.
The Anabolic Effects Of Progesterone

 

[Drareg]

Explains why Peat suggests even for women in menopause to not use continuously. IIRC he has mentioned both take 5 days off and take 14 days off like in a normal cycle. Excuse me if I am wrong.

Thanks Lisa,it seems some people have missed this point.

 

[Drareg]

thankyou @PakPik and @tyw for excellent responses.

@haidut - the aim of the thread is not to cause feelings of uncertainty, but as has been mentioned, to raise awareness, and was written in curiosity, as i was unaware of those effects myself as a practitioner. it was pure interest as to the means why which the body would employ this mechanism.

this forum would be pretty boring if all it contained were affirmations of what most readers clearly think is correct thinking already by Peat. It appears that is exactly what some users are looking to achieve....any time something is called into question, not even for reasons of sowing doubt, the default response is agitation and frustration and even anger...

if one were to look back at the initial post, one owuld see presentation of an article, and the word "discuss"

it seems that is what is unfolding, and this, as @PakPik says, can only lead to higher level sof understanding and confidence

This is a clear strawman.
When we call your opinions into question we get the cliched response of dogma,Peat fanatics etc.

Understanding the context of use is crucial here,not cherry picking contexts which imo can be construed as having a particular angle.
Not one mentioned of blood tests in any of the claims so far,this would be interesting to know,is it an estrogen dump for example.

Did you cycle progesterone @whodathunkit?

You asked to discuss the scribble pad article,you posted studies after the fact.

Is it possible to see the emails from Peat you mentioned for the discussion and all?
Thanks.:)

 

[Drareg]

:)

@haidut You keep avoiding the points/facts raised on progesterone immunosuppressive effects.

The fact that it is not listed as an immunosuppressant on WikiPedia doesn't automatically prove that it isn't . Or does every immunosuppressant that exists on the Earth have to be listed on WikiPedia, and if it is not listed there, then it isn't one? You're not adding anything to the argument here by mentioning that. You seem to be avoiding the argument haidut, I am sorry to say.​

Your claim: "Progesterone does at most a reduction in the activation but not the efficacy."

You're wrong, it does both things.​

You claim: "When you call something immunosuppressive, most people here do not bring up mental images of inducing T regulatory cells. They think of something that represses their ability to fight infection or increases chances of establishing new one, or being used in one of the scenarios I mentioned above - autoimmune "treatment", organ transplant rejection, sepsis treatment, etc."

And what do you think that a powerful induction of T regulatory cells achieve? It impairs ability to fight infections, lowers the so-called autoimmunity reactions, and increases the chances of establishing newinfections. Have you studied what T-regulatory/T-suppressive cells do? That's exactly some of the things they can do.

With "immunosuppression" the definition of wikipedia is good, and it fits what progesterone can do. If by the word immunosuppression people are lead to think of cyclosporin, well, that's something entirely cultural. Let's stick to the scientific (not cultural) definition of an immunosuppressant, even to the wikipedia one, please: and progesterone fits in it.​

You say: "My comments were not directed strictly at you but towards the general idea of this thread - i.e. somehow lumping progesterone with other officially labelled immunosuppressive steroids and raising concerns about its use"

First of all, I'd recommend that if you have anything to say regarding posts not written by me, do it in a separate message and refer to specific person who said so. Your message was a response to my message and you started mixing in how all of the progestin subject was suspicious, etcetera. Problem is, @haidut, I didn't claim any of that, and I am in agreement with you. So you threw that in what was basically your response to me, a rebuttal to something I didn't even say and something I don't even believe? That my friend, is dishonest, I hope you did it cluelessly/unintentionally.​

In the end you didn't provide any single proof to nullify or show how false the already studied and discovered immunosuppressive actions of progesterone are -which they aren't, but I want to learn about nuances-.​

You say: "To convey a sense of uncertainty about progesterone by using a term most people associate with very negative events?"

Why should we not use the term "immunosuppressive" if it is technically correct? Why the censorship? That's my question. Because some people would get offended, fearful and associate negative things with progesterone? That doesn't make sense. And why do you presume that people such as me want to convey a "sense of uncertainty" by trying to understand more deeply progesterone immunological effect? If anything, by understanding more deeply what progesterone does, there should be a reduction in uncertainty.​

You claim: "Calling progesterone immunosuppressive and raising vague doubts about its role in viral infections (where the evidence is mixed) is neither actionable nor beneficial (IMO)"

Haidut, it has been you who have posted references on studies that backfire on your poor attempts to muddle the conversation (I say muddle because of your complete avoidance of the main points on the table). It's not my fault you picked those studies, which end up discrediting you. You're the one adding confusion. What could have been much straightforward, insightful, fruitful, clear exchanges, have been muddled post after post by you and other posters who do nothing but block the conversation and add nothing to either agree with it, or disprove it. You're the one introducing confusion and vagueness one.​

You claim: "Having a thread that simply raises doubt by using a term with very specific (and largely negative) meaning while providing very little actionable information is pointless."

Once again, the fact that a supplement can have some negative action on some context doesn't mean that I am being "negative" about the supplement.

How can we get to "actionable information" if we aren't even able to discuss the properties of progesterone on the immune system? We haven't even been able to discuss those properties, so that then we could maybe conclude useful/insightful things. If you were so interested to get to convey "actionable steps" we'd be all participating and learning from a conversation on the immunological properties of progesterone, and at the end share the insights. But you and other people have only tried to block and deviate what some of us are trying to learn/share.​

Finally, in the same sentiment: I've seen @tyw present very well constructed and researched arguments and explanations, he offers almost full valid support to what he claims, and when it becomes too evident that he is onto something and you're not providing proof why he is wrong, whilst oftentimes you having a weak/invalid argument, then you resort to the 'but what are the "actionable steps"' to kind of devalue/exit what he has argued or him pointing out your faulty arguments. All the meanwhile many posters start to mock Tyw and said false, demeaning things about him without offering a single true rebuttal to what he posts -seems to me you are all afraid of him-.​

I'm sorry, but this is all wrong and very destructive. Again you're providing nothing but avoidance and irrelevancy. I do hope it is not intentional. I hoped to learn and discuss together.​

I hope the best for you, haidut.​

If you can show any posts where there isn't questionable evidence around what tyw is claiming? It's basically other people's work he is bringing to the forum which is fine,the problem is making matter of fact claims when the evidence is lacking should be questioned. Why get upset about this?
I don't see name calling as you state,one poster was upset with the tone of the posts,for example Chris masterjohn believes PUFA is essential and does a great job of articulating it,a lot of masterjohns work is been poorly recommunicated over here.

Ray Peat wrote a book on progesterone,this is the Ray Peat forum with an open bias so people can learn about his views,people are fed up with the many thousands of views out there that gave no healing to them,Peat has given many help in different areas,he offers no magic solution for ill health,you can learn about Peat and then go wherever you like for more. Peat is very much projecting forward about the potentialities that exist,similar aspirations are on here like haidut for example,
Some just want to experiment and links to the scribble pad article which is alarmist in nature worries people, particular if they are new to all of this.
Trying to freeze and alarm people with views we don't bounce off Peat isn't fair imo.
Please remember pakpik the thread asked to discuss the scribble pad article which is vast in scope.
The point then is why not email him and get his view and bring him in on the discussion? If you really wanted an objective discussion you would bring a guy into the conversation who wrote a book on it and likes to keep up to date on it.

What happens pakpik is posters take the easy road of posting some evidence that contradicts Peat and then ask like you are to debunk it,their is an abundance of research for the establishments view ,for example PUFA being essential is a given for them,Peat has the door open on it,a few years ago PUFA should be had in abundance according to the establishment now it's getting lower,Peat a few years ago has said keep it lower.
A pattern that unfolds is you and others may ignore posts like suchsaturations which is short but vast in meaning while sticking to a bias while claiming others on here have the bias because we don't jump on every research bandwagon that claims progesterone is bad.

Either way the man Peat is open to change,clear as day.

Perhaps at this point pakpik you could condense down what it is the point your making with the proof you claim to have and we can get back on track or maybe start a new thread as this one implies we should discuss the scribble pad article.

For me it seems there is a concerted effort at times to attack haidut who somehow has to be perfect on this forum,I think there is also envy at times,he has the courage to get involved almost daily in dialogue in an attempt to help others, some other posters take time and just pop up with study ammo from the mainstream view to appear intelligent and fly away.

Thanks.:)