Wooo's "Progesterone, The Master Hormone Myth"

[InChristAlone]

If progesterone is so immunosuppressive why don't more pregnant women get infections?? I had 2 healthy pregnancies and barely had a cold in either of them. I did get food poisoning in the 2nd but recovered in a couple days. I've been on progest-e for 2.5 yrs and get a cold maybe once a year. I didn't even get sick this winter when everyone else had gotten sick at least twice.

 

[Drareg]

If progesterone is so immunosuppressive why don't more pregnant women get infections?? I had 2 healthy pregnancies and barely had a cold in either of them. I did get food poisoning in the 2nd but recovered in a couple days. I've been on progest-e for 2.5 yrs and get a cold maybe once a year. I didn't even get sick this winter when everyone else had gotten sick at least twice.

Great question Janelle,I'm curious to this fact as I mentioned earlier.
It would make sense that some women have naturally higher progesterone levels,are they having issues a lot compared to others?

 

[haidut]

If progesterone is so immunosuppressive why don't more pregnant women get infections?? I had 2 healthy pregnancies and barely had a cold in either of them. I did get food poisoning in the 2nd but recovered in a couple days. I've been on progest-e for 2.5 yrs and get a cold maybe once a year. I didn't even get sick this winter when everyone else had gotten sick at least twice.

Excellent point! Let's hear what the definition crowd would chime in with.

 

[tyw]

If progesterone is so immunosuppressive why don't more pregnant women get infections?? I had 2 healthy pregnancies and barely had a cold in either of them. I did get food poisoning in the 2nd but recovered in a couple days. I've been on progest-e for 2.5 yrs and get a cold maybe once a year. I didn't even get sick this winter when everyone else had gotten sick at least twice.

Excellent point! Let's hear what the definition crowd would chime in with.

The statistics and possible mechanics for increased infection were already laid out in my previous post -- Wooo's "Progesterone, The Master Hormone Myth"

I will link the paper again -- Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis

This is another paper showing the same observations, with a clear and significant increase in infection risk, with clearly measured immune system shifts -- Pregnancy and Infection

It is good that Jannelle525 did not receive any infections during pregnancy. In today's modern world, that risk has been diminished thanks to good sanitation.

However, that is one case, and the observations of many people, both using the formal scientific method, and from anecdotal evidence (including a few people who posted in this thread), show that the immune system shifts away from the machinery needed to deal with foreign pathogens during pregnancy. I and PakPik have already discussed why this is likely a progesterone mediated effect.

Also, "cold / flu symptoms" tend to be associated with the "auto-immune" type disorders. A suppressed immune system does not manifest a cold.

In terms of ensuring healthy pregnancy, it is important to watch out for infections during those periods, and to treat them quickly. Awareness of the potential risk helps to prepare for it should the need arise.

....

 

[Drareg]

i have no idea if by mentioning progestins she is assuming they act similarly. given the style in which this is written, and her references to administration, i would assume it is likely, i will need to message to find out.

however, in a private discussion with @tyw on facebook, these articles were gleaned

Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies - Nature Medicine
> Compared to our previous experience with untreated female macaques, progesterone treatment facilitated consistent SHIV89.6PD infection with a lower virus inoculum (M.G.L., manuscript in preparation).

Direct and Indirect Inhibition of Th1 Development by Progesterone and Glucocorticoids | The Journal of Immunology
> In the presence of progesterone, activated human lymphocytes, especially γδ T cells, synthesize a 34-kDa molecule (progesterone-induced blocking factor) that inhibits NK activity and exerts an antiabortive effect in vivo

> We have shown here that the local progesterone levels found at the human placenta could directly affect T cell differentiation in the absence of other types of cells and that Th1 development was significantly suppressed by progesterone at concentrations observed in sera during pregnancy.

Estradiol Regulates Susceptibility following Primary Exposure to Genital Herpes Simplex Virus Type 2, while Progesterone Induces Inflammation
> With an inoculation dose of 105 PFU, the saline- and P4-treated mice were found to be highly susceptible to genital HSV-2 infection
> Both groups had extensive pathology and high viral titers in vaginal secretions, and 100% of mice succumbed by day 4 postinfection.
> E2-treated mice were protected from HSV-2 infection at the same dose and did not display any vaginal pathology or viral shedding.
> An analysis of the genes in the vaginal tissue showed that inflammation in the P4-treated group correlated with local induction of chemokines and chemokine receptors that were absent in the E2-treated mice and in uninfected P4-treated mice.

(P4 is progesterone. E2 is estrogen. HSV-2 is Herpes Simplex Virus 2)

***Direct quote from TYW***
Some of the studies suggest a shift from Th1 mediated immunity to Th2 mediated immunity with increasing progesterone levels.
somewhat makes sense, since the Th1 stuff is usually thought to be responsible for defence against extracellular pathogens (like bacteria and viruses).

We suggest that perhaps the immunosuppression is of a controlled quality in order to maximise epigenetic viral signalling.
This is what i hoped to discuss...

In the first study do they inject HIV virus directly into the vagina?

"There are several limitations of these experiments and this animal model of mucosal infection. To perform experiments resulting in consistent infection of control monkeys, we treated female macaques with progesterone 30 days before vaginal challenge. This treatment causes thinning of the vaginal epithelium10 and facilitates infection with SHIV89.6PD (our unpublished results). We do not know how this alteration in the mucosal environment affected the transudation of antibody across vaginal mucosa16, but it is possible that this allowed more antibody to cross to the mucosal surface. Also, the vaginal changes induced with a high intramuscular dose of progesterone are probably more dramatic than changes that occur during the normal female menstrual cycle. Although this vaginal challenge macaque model may allow general conclusions about the role of antibody in protection, mucosal exposure, and transmission of HIV-1 in humans is clearly a complex interaction that is affected by variables not considered in these experiments."

Did they even check the maques natural progesterone levels before hand?
As mentioned they used medroxyprogesterone acetate and don't cycle it.
Did they use a needle straight to the vagina?

The monkeys were also captive bred, this is stressful for them and getting needles in the vagina and progesterone for 30 days straight I'm sure was a real hoot.

 

[Drareg]

The statistics and possible mechanics for increased infection were already laid out in my previous post -- Wooo's "Progesterone, The Master Hormone Myth"

I will link the paper again -- Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis

This is another paper showing the same observations, with a clear and significant increase in infection risk, with clearly measured immune system shifts -- Pregnancy and Infection

It is good that Jannelle525 did not receive any infections during pregnancy. In today's modern world, that risk has been diminished thanks to good sanitation.

However, that is one case, and the observations of many people, both using the formal scientific method, and from anecdotal evidence (including a few people who posted in this thread), show that the immune system shifts away from the machinery needed to deal with foreign pathogens during pregnancy. I and PakPik have already discussed why this is likely a progesterone mediated effect.

Also, "cold / flu symptoms" tend to be associated with the "auto-immune" type disorders. A suppressed immune system does not manifest a cold.

In terms of ensuring healthy pregnancy, it is important to watch out for infections during those periods, and to treat them quickly. Awareness of the potential risk helps to prepare for it should the need arise.

....

From the study you linked.
"Importantly, pregnant females are not immunosuppressed"

 

[tyw]

From the study you linked.
"Importantly, pregnant females are not immunosuppressed"

Please, quote the statement in full.

This is a single statement in the "Introduction" section of the paper 'Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis', by Dionne P. Robinson and Sabra L. Kleina -- Pregnancy and Infection

The statement and surrounding context was:

Importantly, pregnant females are not immunosuppressed, but rather their immune responses are biased toward an anti-inflammatory phenotype that influences not only the outcome of pregnancy but disease pathogenesis as well.

Figure 1 -- Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis

During the three trimesters of pregnancy, there is a shift in the balance of proinflammatory and anti-inflammatory responses. By the third trimester, anti-inflammatory responses, including the activity of M2 macrophages, Th2 cells, and regulatory T cells, are elevated and inflammatory responses, including the activity of NK cells, M1 macrophages, and Th1 cells, are reduced. Changes in the concentrations of sex steroids, including estradiol, estriol, and progesterone, lead to the immunological shifts during pregnancy.

The hormonal and immunological changes that occur over the course of pregnancy are necessary to support a healthy pregnancy, but also dramatically affect female susceptibility to autoimmune and infectious diseases.​

The paper then goes on to describe exactly the significant increases in infection rates, while decreasing the rate of autoimmune diseases. This is what is expected from the shift away Th-1 dominance and towards Th-2 dominance, which is also discussed in the papers.

I have used the term "Immune shift" to describe this. This shift does suppress the innate immune system, and adaptive immune system's Th-1 arm, and thus leading to higher infection rates. This is "immunosuppression" (of the stated components of the immune system)

Since it is relevant, I shall reproduce the section on Progesterone here. Reading the full paper is recommended for full context.

Progesterone

Progesterone is produced by the corpus lutea in the ovaries in non-pregnant females and by the placenta during pregnancy, playing a critical role in reproduction and immune function. Progesterone is typically regarded as anti-inflammatory. Progesterone receptors (PRs) have been identified in epithelial cells as well as in mast cells, eosinophils, macrophages, DCs, and lymphocytes (Kovats et al., 2010). There are sex differences in PR expression. For example, the expression of PRs is higher in DCs from females, which may explain why P4 is better able to suppress the activity (e.g., secretion of TNF-α) of DCs from female than male rats (Butts et al., 2008). Progesterone can bind to glucocorticoid receptors (GRs), which are more abundant in the immune system than are PRs, and may represent an alternative mechanism for progesterone-induced changes in immune function (Jones et al., 2010). Progesterone inhibits TLR-induced cytokine production as well as surface receptor expression via PRs and GRs in DCs (Jones et al., 2010).

Progesterone suppresses innate immune responses, including macrophage and NK cell activity as well as NF-κB signal transduction (Baley and Schacter, 1985; Furukawa et al., 1984; McKay and Cidlowski, 1999; Miller and Hunt, 1996; Savita and Rai, 1998; Toder et al., 1984). Progesterone can inhibit nitrite and nitric oxide production as well as Tnfα mRNA expression by murine macrophages (Miller et al., 1996; Miller and Hunt, 1998; Savita and Rai, 1998). Elevated concentrations of progesterone during pregnancy inhibit the development of Th1 immune responses and promote production of Th2 immune responses, including IL-4 and IL-5 production (Piccinni et al., 1995; Piccinni et al., 2000). In humans, elevated concentrations of progesterone during the second trimester of pregnancy is correlated with reduced activity of regulatory T cells (Mjosberg et al., 2009). In contrast, in mice, the activity of regulatory T cells is increased at the maternal-fetal interface and in lymphoid tissues in pregnant females and in non-pregnant females exposed to P4 (Kallikourdis and Betz, 2007; Mao et al., 2010). Progesterone also suppresses antibody production (Lu et al., 2002).​

....

 

[InChristAlone]

I am thoroughly confused now. Cold/flu symptoms are auto-immune?? The link Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis talks about how pregnant women are more at risk for severe complications of the flu. That wouldn't be auto-immune if progesterone is immunosuppressive.

It could be said some of these infectious diseases put pregnant women at risk because of malnutrition. I feel like some of those studies are fear-mongering, it really does help sell flu vaccines to pregnant women.

 

[Drareg]

Please, quote the statement in full.

This is a single statement in the "Introduction" section of the paper 'Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis', by Dionne P. Robinson and Sabra L. Kleina -- Pregnancy and Infection

The statement and surrounding context was:

Importantly, pregnant females are not immunosuppressed, but rather their immune responses are biased toward an anti-inflammatory phenotype that influences not only the outcome of pregnancy but disease pathogenesis as well.

Figure 1 -- Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis

View attachment 4968

During the three trimesters of pregnancy, there is a shift in the balance of proinflammatory and anti-inflammatory responses. By the third trimester, anti-inflammatory responses, including the activity of M2 macrophages, Th2 cells, and regulatory T cells, are elevated and inflammatory responses, including the activity of NK cells, M1 macrophages, and Th1 cells, are reduced. Changes in the concentrations of sex steroids, including estradiol, estriol, and progesterone, lead to the immunological shifts during pregnancy.

The hormonal and immunological changes that occur over the course of pregnancy are necessary to support a healthy pregnancy, but also dramatically affect female susceptibility to autoimmune and infectious diseases.​

The paper then goes on to describe exactly the significant increases in infection rates, while decreasing the rate of autoimmune diseases. This is what is expected from the shift away Th-1 dominance and towards Th-2 dominance, which is also discussed in the papers.

I have used the term "Immune shift" to describe this. This shift does suppress the innate immune system, and adaptive immune system's Th-1 arm, and thus leading to higher infection rates. This is "immunosuppression" (of the stated components of the immune system)

Since it is relevant, I shall reproduce the section on Progesterone here. Reading the full paper is recommended for full context.

Progesterone

Progesterone is produced by the corpus lutea in the ovaries in non-pregnant females and by the placenta during pregnancy, playing a critical role in reproduction and immune function. Progesterone is typically regarded as anti-inflammatory. Progesterone receptors (PRs) have been identified in epithelial cells as well as in mast cells, eosinophils, macrophages, DCs, and lymphocytes (Kovats et al., 2010). There are sex differences in PR expression. For example, the expression of PRs is higher in DCs from females, which may explain why P4 is better able to suppress the activity (e.g., secretion of TNF-α) of DCs from female than male rats (Butts et al., 2008). Progesterone can bind to glucocorticoid receptors (GRs), which are more abundant in the immune system than are PRs, and may represent an alternative mechanism for progesterone-induced changes in immune function (Jones et al., 2010). Progesterone inhibits TLR-induced cytokine production as well as surface receptor expression via PRs and GRs in DCs (Jones et al., 2010).

Progesterone suppresses innate immune responses, including macrophage and NK cell activity as well as NF-κB signal transduction (Baley and Schacter, 1985; Furukawa et al., 1984; McKay and Cidlowski, 1999; Miller and Hunt, 1996; Savita and Rai, 1998; Toder et al., 1984). Progesterone can inhibit nitrite and nitric oxide production as well as Tnfα mRNA expression by murine macrophages (Miller et al., 1996; Miller and Hunt, 1998; Savita and Rai, 1998). Elevated concentrations of progesterone during pregnancy inhibit the development of Th1 immune responses and promote production of Th2 immune responses, including IL-4 and IL-5 production (Piccinni et al., 1995; Piccinni et al., 2000). In humans, elevated concentrations of progesterone during the second trimester of pregnancy is correlated with reduced activity of regulatory T cells (Mjosberg et al., 2009). In contrast, in mice, the activity of regulatory T cells is increased at the maternal-fetal interface and in lymphoid tissues in pregnant females and in non-pregnant females exposed to P4 (Kallikourdis and Betz, 2007; Mao et al., 2010). Progesterone also suppresses antibody production (Lu et al., 2002).​

....

It's an open forum,you don't get dictate,you skirt points regularly just like with janelle's points on infection.

"Importantly, pregnant females are not immunosuppressed, but rather their immune responses are biased toward an anti-inflammatory phenotype that influences not only the outcome of pregnancy but disease pathogenesis as well."

The statement reads pregnant females are not immunosuppressed.

"There is a paucity of data on immune responses to influenza virus infection during pregnancy".

No mention of thyroid function,hypo or hyper.
They end the study by saying the below.
"Hormones are the driving factors behind changes in immune function and disease susceptibility during pregnancy"

 

[tyw]

I am thoroughly confused now. Cold/flu symptoms are auto-immune?? The link Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis talks about how pregnant women are more at risk for severe complications of the flu. That wouldn't be auto-immune if progesterone is immunosuppressive.

It could be said some of these infectious diseases put pregnant women at risk because of malnutrition. I feel like some of those studies are fear-mongering, it really does help sell flu vaccines to pregnant women.

The initial symptoms of cold, like mucous production, coughing, etc .... are an inflammatory response to a pathogen. It is these symptoms that an immune-suppressed individual will not experience.

However, the secondary complications of the influenza virus, like pneumonia will become more severe. This is why I say we cannot judge infection risk based on initial symptoms. This is also the type of behaviour observed by some of the posters in this thread, the "I generally felt really good, until I was suddenly sick" observation. This is a common progression during immune suppression.

----

As for modern day vaccines, that is a separate topic. I am personally very much against any and all vaccinations, but the blame for that lies on the people who want to explicitly promote the use of vaccines, and not on researchers who are doing a research review of pregnancy and its effects on the immune system.

We should separate the observed mechanisms of pregnancy-associated immunosuppression, from the necessary intervention. Knowing the mechanisms helps the reader make better decisions, and choose the correct intervention for themselves.

----

@Drareg, I think it is fair to quote the entire sentence, not just a part of the sentence, and then interpret it within the context of the source where the sentence came from.

If one wants to debunk the evidence of a source, it is also fair to read the entire source. In this case, there is abundant evidence for the increased risk of infection, and as to how suppression of specific parts of the immune system is qualified.

....

 

[InChristAlone]

I know when I did try going off progesterone for a month I began having what I would call brain on fire with panic attacks. Maybe I tend towards autoimmune. I have no idea. Thanks to progesterone and cyproheptadine I am not so catabolic as I was for years after birth.

I did have a gastro infection during pregnancy and I did have thoughts of complications, but it progressed exactly how it would if I wasn't pregnant. Maybe food poisoning isn't so much a risk to pregnant women. But they always say to be mindful of listeria and things like that and I was also doing raw milk and raw cheese. Haha completely going against recommendations.

 

[Drareg]

The initial symptoms of cold, like mucous production, coughing, etc .... are an inflammatory response to a pathogen. It is these symptoms that an immune-suppressed individual will not experience.

However, the secondary complications of the influenza virus, like pneumonia will become more severe. This is why I say we cannot judge infection risk based on initial symptoms. This is also the type of behaviour observed by some of the posters in this thread, the "I generally felt really good, until I was suddenly sick" observation. This is a common progression during immune suppression.

----

As for modern day vaccines, that is a separate topic. I am personally very much against any and all vaccinations, but the blame for that lies on the people who want to explicitly promote the use of vaccines, and not on researchers who are doing a research review of pregnancy and its effects on the immune system.

We should separate the observed mechanisms of pregnancy-associated immunosuppression, from the necessary intervention. Knowing the mechanisms helps the reader make better decisions, and choose the correct intervention for themselves.

----

@Drareg, I think it is fair to quote the entire sentence, not just a part of the sentence, and then interpret it within the context of the source where the sentence came from.

If one wants to debunk the evidence of a source, it is also fair to read the entire source. In this case, there is abundant evidence for the increased risk of infection, and as to how suppression of specific parts of the immune system is qualified.

....

The common progression with progesterone feeling good then bad you mention could as easily be from not cycling progesterone,this applies to men,if everybody would sincerely tell us their dosage and for how long we would better informed.
If the researchers in the studies you posted are not cycling the progesterone or testing the natural levels present in the maques monkeys then what is the point of the studies.

I did read it hence my questions about thyroid function not being measured in this paper.
If both you and pakpik believe that thyroid function would not be relevant here I'm all ears......

 

[haidut]

The initial symptoms of cold, like mucous production, coughing, etc .... are an inflammatory response to a pathogen. It is these symptoms that an immune-suppressed individual will not experience.

However, the secondary complications of the influenza virus, like pneumonia will become more severe. This is why I say we cannot judge infection risk based on initial symptoms. This is also the type of behaviour observed by some of the posters in this thread, the "I generally felt really good, until I was suddenly sick" observation. This is a common progression during immune suppression.

----

As for modern day vaccines, that is a separate topic. I am personally very much against any and all vaccinations, but the blame for that lies on the people who want to explicitly promote the use of vaccines, and not on researchers who are doing a research review of pregnancy and its effects on the immune system.

We should separate the observed mechanisms of pregnancy-associated immunosuppression, from the necessary intervention. Knowing the mechanisms helps the reader make better decisions, and choose the correct intervention for themselves.

----

@Drareg, I think it is fair to quote the entire sentence, not just a part of the sentence, and then interpret it within the context of the source where the sentence came from.

If one wants to debunk the evidence of a source, it is also fair to read the entire source. In this case, there is abundant evidence for the increased risk of infection, and as to how suppression of specific parts of the immune system is qualified.

....

An option we have not explored and for which there is probably not much evidence currently (for or against) is that the suppressed immune response is a result of progesterone improving the underlying pathology and hence no need for a robust immune response. As I mentioned before, the morphostatis theory would predict such an effect for a steroid that stabilizes the cell and reduces leakage of intracellular material into the bloodstream.
As an example of such a "side effect", NSAIDs lower cortisol in states with high inflammation but they are not anti-glucocorticoid (except aspirin which directly lowers 11b-HSD1). Neither are they pro-inflammatory (duh), which by one official definition they can be labelled as anything that lowers cortisol can be considered pro-inflammatory. Anyways, the study below found that the "immunosuppression" by progesterone was NOT caused through the GR. Thus, the immunomodulatory effects of progesterone are likely much more nuanced than a simple label of an immunosuppressant (like cortisol) would make us believe.
Progesterone-induced immunosuppression is not mediated through the progesterone receptor | Human Reproduction | Oxford Academic
"...We also used the glucocorticoid receptor antagonist RU 43044 to address the hypothesis that progesterone exerts immuno-modulatory effects via interactions with the glucocorticoid receptor. Both hydrocortisone (10–6 and 10–7 M) and progesterone (10–5, 10–6 and 10–7 M) inhibited phytohaemagglu-tinin-induced lymphocyte proliferation in a dose-dependent fashion. RU 43044 (10–5 M) significantly reversed the immunosuppressive effect of hydrocortisone but not that of progesterone. These studies indicate that human PBMCs do not express the classical progesterone receptor. Our results further suggest that progesterone does not mediate its immunomodulatory effects via interaction with the glucocorticoid receptor. Interaction with other members of the steroid and thyroid hormone receptor superfamily, local conversion to other steroid substances or non-classical receptor-mediated mechanisms may be involved."

I don't know if there is a test for direct immunosuppression (as there is for pro- or anti-glucocorticoid) as there is no single immune "receptor". But if you know of such a thing or a way to test for that I am all ears. The evidence we have so far is that progesterone may suppress the immune activation but usually improves the pathology and outcome in viral conditions. A true immunosuppressant would be expected to both suppress immune response and worsen the pathology. Both cortisol and estrogen fall into the latter category, but progesterone does not. Hence my hunch that the presence of supraphysiological levels if progesterone is simply a signal that there is no need to ramp up the immune response, but progesterone is not directly inhibiting the function of various immune subsystems (except maybe for direct inhibition of NO, histamine and serotonin release).

 

[haidut]

As mentioned they used medroxyprogesterone acetate and don't cycle it

I don't think the study on HIV they gave is a valid example. MPA is nothing like progesterone. Aside form the agonism of the PR they have very little in common.
Medroxyprogesterone acetate - Wikipedia

"...MPA is a potent full agonist of the AR. Its activation of the AR has been shown to play an important and major role in its antigonadotropic effects and in its beneficial effects against breast cancer.[100][104][105] "

"...As an agonist of the GR, MPA has glucocorticoid activity, and as a result can cause symptoms of Cushing's syndrome,[111] steroid diabetes, and adrenal insufficiency at sufficiently high doses."

Neither one of these is a property of progesterone, at least not the causing of Cushing syndrome and diabetes. Synthetic progestins are well known to induce Cushing, bioidentical progesterone is not. In fact, I make an open call to everyone who thinks progesterone is a GR agonist to show me a case study or a full study where progesterone induced Cushign syndrome.
The GR agonism of MPA alone can definitely explain the immunosuppressive effects seen in the HIV study, and as I mentioned in my response to tyw above (Wooo's "Progesterone, The Master Hormone Myth"), the "immunosuppression" by progesterone does not seem to be done through the GR.

 

[Mito]

The initial symptoms of cold, like mucous production, coughing, etc .... are an inflammatory response to a pathogen. It is these symptoms that an immune-suppressed individual will not experience.

So is there any practical way to know if it is "immune suppression" or "immune strength" that is causing a lack of cold symptoms? For example, if a person doesn't experience any cold symptoms (or other illnesses symptoms) for more than a year or two? How would one know if the immune system killed the virus before it could replicate or if it was just lack of a strong immune response (and therefore no symptoms)? I'm making the assumption that one was exposed to a cold virus at least once per year since the average is 1 to 2 colds per year for adults.

 

[haidut]

So is there any practical way to know if it is "immune suppression" or "immune strength" that is causing a lack of cold symptoms? For example, if a person doesn't experience any cold symptoms (or other illnesses symptoms) for more than a year or two? How would one know if the immune system killed the virus before it could replicate or if it was just lack of a strong immune response (and therefore no symptoms)? I'm making the assumption that one was exposed to a cold virus at least once per year since the average is 1 to 2 colds per year for adults.

I would like to hear an answer to that too. My take it that currently there is no way to distinguish between immune suppression and immune strength definitively, except waiting for the pathology to unfold itself and if you survive it was immune strength, otherwise immune weakness. Biomarkers like WBC or even a full CBC are not definitive as they can be skewed in one direction or another based on other pathology. For instance somebody with leukemia would typically have high WBC and look like a person with strong immune response but even a cold can kill them easily. On the contrary, somebody with low WBC would looks immunosuppressed but it can be simply due to low PUFA stores or low inflammation. Peat wrote about the guy on fat free diet whose WBC dropped below normal but he was quite healthy. People with low CRP or low ESR often have WBC below the normal limit and they are certainly not immunosuppressed. I have also seen it in EFA defiicient people too - low WBC but no higher infection risk of any kind.
Anyways, if there is a definitive test then I want to get some more info on that.

 

[Regina]

An option we have not explored and for which there is probably not much evidence currently (for or against) is that the suppressed immune response is a result of progesterone improving the underlying pathology and hence no need for a robust immune response. As I mentioned before, the morphostatis theory would predict such an effect for a steroid that stabilizes the cell and reduces leakage of intracellular material into the bloodstream.
As an example of such a "side effect", NSAIDs lower cortisol in states with high inflammation but they are not anti-glucocorticoid (except aspirin which directly lowers 11b-HSD1). Neither are they pro-inflammatory (duh), which by one official definition they can be labelled as anything that lowers cortisol can be considered pro-inflammatory. Anyways, the study below found that the "immunosuppression" by progesterone was NOT caused through the GR. Thus, the immunomodulatory effects of progesterone are likely much more nuanced than a simple label of an immunosuppressant (like cortisol) would make us believe.
Progesterone-induced immunosuppression is not mediated through the progesterone receptor | Human Reproduction | Oxford Academic
"...We also used the glucocorticoid receptor antagonist RU 43044 to address the hypothesis that progesterone exerts immuno-modulatory effects via interactions with the glucocorticoid receptor. Both hydrocortisone (10–6 and 10–7 M) and progesterone (10–5, 10–6 and 10–7 M) inhibited phytohaemagglu-tinin-induced lymphocyte proliferation in a dose-dependent fashion. RU 43044 (10–5 M) significantly reversed the immunosuppressive effect of hydrocortisone but not that of progesterone. These studies indicate that human PBMCs do not express the classical progesterone receptor. Our results further suggest that progesterone does not mediate its immunomodulatory effects via interaction with the glucocorticoid receptor. Interaction with other members of the steroid and thyroid hormone receptor superfamily, local conversion to other steroid substances or non-classical receptor-mediated mechanisms may be involved."

I don't know if there is a test for direct immunosuppression (as there is for pro- or anti-glucocorticoid) as there is no single immune "receptor". But if you know of such a thing or a way to test for that I am all ears. The evidence we have so far is that progesterone may suppress the immune activation but usually improves the pathology and outcome in viral conditions. A true immunosuppressant would be expected to both suppress immune response and worsen the pathology. Both cortisol and estrogen fall into the latter category, but progesterone does not. Hence my hunch that the presence of supraphysiological levels if progesterone is simply a signal that there is no need to ramp up the immune response, but progesterone is not directly inhibiting the function of various immune subsystems (except maybe for direct inhibition of NO, histamine and serotonin release).

Phew!

 

[Drareg]

I would also like to see the free fatty acid profile during all trimesters of said pregnancies.
Are these women in question obese is another factor,even if not ,excess PUFA needs to be looked at in relation to inflammatory responses.
Thanks everyone

 

[lollipop]

@haidut Okay I found where I had heard the idea of "5 days off" for menopausal women - not Ray - but Dr. John Lee's website:

"Q: What is the recommended dosage of progesterone?

A: For premenopausal women the usual dose is 15-24 mg/day for 14 days before expected menses, stopping the day or so before menses.

For postmenopausal women, the dose that often works well is 15 mg/day for 25 days of the calendar month."

Progesterone Cream: Frequently Asked Questions (FAQ's) by Dr. Lee

 

[haidut]

@haidut Okay I found where I had heard the idea of "5 days off" for menopausal women - not Ray - but Dr. John Lee's website:

"Q: What is the recommended dosage of progesterone?

A: For premenopausal women the usual dose is 15-24 mg/day for 14 days before expected menses, stopping the day or so before menses.

For postmenopausal women, the dose that often works well is 15 mg/day for 25 days of the calendar month."

Progesterone Cream: Frequently Asked Questions (FAQ's) by Dr. Lee

Cool thanks. I think the cycling need in women is self-evident, as to not disrupt the normal menstrual cycle. But I have not seen the rationale for cycling in postmenopausal women. Does he say why the 5 days off for them as well?
I am also interested if there is any information on cycling in men - specifically for pregnenolone, progesterone and DHEA. My own experiments show that it may be necessary and some human studied support that idea (at least for DHEA) but it would be nice to hear Peat say something about it.