Not Quite Ready For Progesterone

yerrag

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There is a lot said about how protective progesterone is. It has also been said though that steroids that are downstream of another steroid are less safe to use, an example being that progesterone is less safe to use than pregnenolone. Today, I'd like to share an example of how progesterone can be unsafe to use, especially when one doesn't fully understand the context of its use. Before I proceed, I want to let you know that a lot of what I'm saying is very much based on my thought process - of connecting the dots of what's transpired, with the benefit of hindsight.

I have been very careful with the use of supplements, especially when it involves steroids and hormones. I thought I was prepared to use Progestene as my first hormone to use. I had hoped to use very small quantities of it on a mother rat, as the rat was suffering from UTI regularly, and I had envisioned using some natural substances that would fix the problem of incontinence of the rat. I selected Progestene, and I wasn't disappointed in its potency when I would feel energized just using it to rub a few drops on the rat, with me getting the spillover effect. I would get things done quickly, and I would not say "manana" or tomorrow when it's something that can be accomplished today.

Knowing how good it is, I didn't want to use a large dose on the rat. Yet when I applied the dose on the rat, the result was temperature jumping about 0.8 C, to a point where it is 0.3 C above a rat's normal healthy temperature. It also increase the pulse around 30-40 beats above the usual rate (per minutes). The blood pressure also spiked up. It eventually subsided when I stopped dosing.

I was afraid to use this the next day, and I stopped its use. But over the next few days, I used it sporadically. One day at a third of the dose, stopping it the next day, and following it up with another third of the dose. During all this time, it escaped my notice that it was getting more difficult to get a consistent blood pressure and pulse reading. That was when I realized that it was because I was now dealing with arrhythmia, or irregular heart beat.

I started to use bag breathing on the rat, as I also noticed that this coincided with it having a rapid breathing rate. It helped lower it to a normal rate. Yet the arrhythmia did not go away.

At this point, I should have gotten concerned, but I thought the arrhythmia would be a passing thing, having read that progesterone would help with such a situation. Yet, I wasn't willing to face what I'm seeing, instead insisting that more Progestene would help.

So, this morning I put in a dose of Progestene, thinking it would help further. I wouldn't know if it did know, because the rat apparently had another bout of high temperatures, pulse, and blood pressure, and the breathing was very labored. Bag breathing made the rat worse off, and her oxygen SpO2 went down from 93 to 74. The rat was very uncomfortable, her eyes were wide open, mouth was quivering, and limbs were flapping and it was hard to take readings. It turns out when taken to the rat ER that the rat had aspirated, and I realized I had been too focused on the effects of Progestene that I lost sight of the signs of aspiration and its synptoms on wide display to me.

As I was driving back home from the vet, I thought about the events and ruminated. I thought about the arrhythmia and asked myself how that had occurred. Here's how I see it: The rat has signs of being hypothyroid. It was never confirmed. But the rat's ECG showed a long QT interval. When in doubt, I should always assume the subject is hypothyroid. To err on the side of safety.

Being in a hypothyroid condition meant the rat wasn't running on all four cylinders. It wasn't running on efficient metabolism, and more likely it wasn't producing enough carbon dioxide. When the progesterone kicked up the metabolism to high gear, the rest of the rat had to keep up with it. But being hypothyroid, the rat was running low on oxygen because it was running low on carbon dioxide. Lacking oxygen would result in the rat having a hard time catching up with its breathing, and lacking carbon dioxide, the blood would become alkaline, and this would throw the electrolytes off balance (calcium, sodium, potassium, magnesium). This would make the heart strain and not be able to fully complete its repolarization phase. Hence, the arrhythmia.

For me, this experience shows how important it is to build the body up to tackle the demands of using very powerful substances meant to bring the body to a higher energy level. If the body cannot step up to the demands of a high energy level, and is forced to catch up, it could be counterproductive and push the body further into dire straits. This reminds me of what naturopathic practitioners call a healing crisis, when during healing the body retraces its past malaises. I understand now it doesn't have to be this way. A healing crisis isn't always good, because if the crisis occurs and the body isn't ready for it, it could really imperil the body.

From this lesson, I now would do better by building the structure by give it the foundational strength, before aspiring to greater heights. There is no quick way to it.
 
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You might be onto something here. I have a buddy who took pregnenolone and got arrhythmia from it. He is probably hypothyroid as well. He is a young man but many young men are hypothyroid. Now he just takes 5 mg of DHEA every other day and this seems to make him feel better.


It's essential to build your base first. So many people look at supplements, and hormones and pro hormones when they should be looking at making sure their nutrition is good and that they're staying warm.


I don't ever take progesterone because it makes my penis numb. I do take a small amount of pregnenolone and DHEA, and a little bit of androsterone. Very small amounts seem to be very helpful.


But I also am pretty good with diet now in terms of a bit of liver or oysters, daily carrot salad, well cooked mushrooms, plenty of carbs and protein, and the major supplements besides the one above are vitamin K2 and a bit of calcium eggshell and sometimes magnesium.


It's impossible to predict sometimes what the effects of some type of supplement or pro hormone will have. Especially if you're already suffering from a low and slow metabolism.
 
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yerrag

yerrag

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The rat was having a heart rate of 164 with arrhythmia. I checked blood and urine tests, and it confirmed respiratory alkalosis. I asked the vet interns what they have available to resolve the respiratory alkalosis condition. They have nothing. They don't even have paper bags. This morning I had the rat on bag breathing for 1 hour, with an oximeter monitoring her SpO2, pulse. It was around the 45th minutes when the heart rate went down to the 80s, half the rate when I started. The rat''s breath rate also went down to 24, from around the 50s.

It was a desperation attempt, a Hail Mary it seemed, and it worked. I may still do more bag breathing, just in case the irregular heart rate condition is not yet resolved.

The rat cardiologist may not be needed anymore, and the dreaded pacemaker would have to find another host.

@co2islife I am sore holding the bag for an hour. Looking forward to getting my carbogenen devices soon.
 
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yerrag

yerrag

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The topical progesterone, I reckon, has a half-life of 40 hours. I guess it would take twice that time for its effect to be felt less. About 3.5 days. Still 18 hours to go. I continue to bag breathe for hour-long lengths.

In the meantime, the rat is just being given dextrose (for sugar). Rat has enough electrolytes in her system, and vitamins. Also, giving red light therapy to boost thyroid. Not able to eat nor drink yet, but with IV dextrose she is well hydrated and kept from running low on sugar. Have declined parenteral nutrition, or even the use of NGT. The food will merely interfere with her recovery, as digestion is an energy-intensive process.

Rat is becoming more active. Maybe after this ordeal, induced by an excess of progesterene, will still produce plenty of protective hormones. It's far from perfect the way it's going, but at this finding light at the end of the tunnel is good enough.
 

DaveFoster

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The rat was having a heart rate of 164 with arrhythmia. I checked blood and urine tests, and it confirmed respiratory alkalosis. I asked the vet interns what they have available to resolve the respiratory alkalosis condition. They have nothing. They don't even have paper bags. This morning I had the rat on bag breathing for 1 hour, with an oximeter monitoring her SpO2, pulse. It was around the 45th minutes when the heart rate went down to the 80s, half the rate when I started. The rat''s breath rate also went down to 24, from around the 50s.

It was a desperation attempt, a Hail Mary it seemed, and it worked. I may still do more bag breathing, just in case the irregular heart rate condition is not yet resolved.

The rat cardiologist may not be needed anymore, and the dreaded pacemaker would have to find another host.

@co2islife I am sore holding the bag for an hour. Looking forward to getting my carbogenen devices soon.
I always make sure to have a few doses of propranolol (Inderal) and clonazepam (Klonopin) on hand just in case something goes wrong. The former can easily save your life in a bad situation.
 

Wagner83

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Ray Peat Email Advice Depository

"It inhibits cholinesterase, and affects microtubules and microfilaments."

Arch Int Pharmacodyn Ther. 1976 May;221(1):21-31.
Cardiac chronotropic mechanisms of dimethyl sulphoxide: inhibition of
acetylcholinesterase and antagonism of negative chronotropy by atropine.

Shlafer M, Matheny JL, Karow AM Jr.
The chronotropic effects of dimethyl sulphoxide (DMSO) were studied in
spontaneously beating rabbit atria. Low concentrations of DMSO (0.14, 0.42 M)
produced slight positive chronotropic (+C) responses; 0.84 and 1.41 M DMSO caused
significant negative chronotropic (--C) responses. All concentrations decreased
contractile strength. Atropine sulphate (10)-7) to 10(-5) M) antagonized the
chronotropic effects, but not the inotropic effects. In the presence of atropine
all DMSO concentrations produced significant +C responses. Reserpine pretreatment
or propranolol did not affect contractile responses to DMSO in the absence or
presence of atropine. DMSO produced concentration-dependent inhibition of
acetylcholinesterase (AChE) activity of atrial homogenates. The results indicate
that the --C responses are due specifically to AChE inhibition by DMSO and
resulting cholinergic influences on the atrial pacemaker. Adrenergic mechanisms
do not appear to mediate the +C responses. Data presented here provide evidence
that a cardioactive effect of DMSO is mediated by a well-defined receptor-linked
mechanism, and that this effect can be modified by a specific receptor blocking
agent.

Indian J Med Res. 1992 Oct;96:275-8.
Inhibition of acetylcholinesterase of mice erythrocytes & synaptosomes by
dimethylsulfoxide.
Jagota SK.
Department of Biochemistry, Panjab University, Chandigarh.
In vitro inhibitory effect of dimethylsulfoxide (DMSO) on acetylcholinesterase of
erythrocyte membranes and synaptosomes of mice was observed using
acetylthiocholine as substrate. DMSO inhibited the enzyme from both sources and
the effect was concentration dependent. It produced an inhibition of 26 to 28 per
cent at a concentration of 0.13 mM and 92 to 95 per cent at a higher
concentration of 1.91 mM. The Km of bound and solubilized enzyme of the
synaptosomes was 0.2 and 0.15 mM while that of erythrocyte membranes 0.5 and 0.33
mM respectively. The Vmax was 0.4 and 0.4 (for synaptosomes) and 0.67 and 0.59
(for erythrocyte membranes) Mmoles/mg protein/min, respectively for bound and
solubilized forms. The Ki of solubilized enzyme of synaptosomes was 0.11 mM.
Kinetic studies showed that the inhibition was competitive in nature.

The reproductive toxicity of DMSO was evaluated in an
in vitro culture of mammalian rodent embryos (Augustine-Rauch et al., 2004,cited in
Annex 2, [ii]). At a concentration of 0.04% in culture media, DMSO
produced significant embryo toxicity, resulting in failure of neural tube
closure.
However, in vitro data is difficult to extrapolate to in vivo responses in humans.
The first (and only) reported study evaluating maternal or developmental toxicity in rats,
found no evidence for reproduction toxicity at doses up to 1000 mg/kg/day
The authors reported the NOAEL for maternal and developmental toxicity as ≥1000
mg/kg/day, the highest dose tested (Magnuson et al., 2007; Annex 2,ii).
DMSO3 exposure to developing mouse brains can produce brain
degeneration (Hanslick et al., 2009). This neurotoxicity could be detected at doses
as low as 0.3 ml/kg (DMSO > 99% pure), a level exceeded in children exposed to DMSO
during certain medical treatments.



I'd be curious to see how you would do with something like Progest-E (no dmso, vitamin E is solvent).
cleardot.gif
 
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yerrag

yerrag

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I always make sure to have a few doses of propranolol (Inderal) and clonazepam (Klonopin) on hand just in case something goes wrong. The former can easily save your life in a bad situation.
Thanks Dave. I'm glad I didn't have to use them this time though. Perhaps the cardiologist brought in would have used these, but since the bag breathing did its job, these drugs weren't used.

"It inhibits cholinesterase, and affects microtubules and microfilaments."
I wonder if you could unpack this statement. Does inbibiting cholinesterase means that it encourages cholinergic activity? And if so, would this slow down bodily processes. Wouldn't the heart rate slow down instead of speed up? Just thinking out loud my confusion.
 

Wagner83

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I wonder if you could unpack this statement. Does inbibiting cholinesterase means that it encourages cholinergic activity? And if so, would this slow down bodily processes. Wouldn't the heart rate slow down instead of speed up? Just thinking out loud my confusion.

Did you check what chronotropic meant?
Chronotropic - Wikipedia
See the highlighted red part in my previous post.
 
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yerrag

yerrag

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Did you check what chronotropic meant?
Chronotropic - Wikipedia
See the highlighted red part in my previous post.
I rechecked my understanding and negative chronotropic describes a decrease in heart rate. Is that correct? So, the use of DMSO would tend to decrease the heart rate. It is consistent with Peat saying it inhibits cholinesterase.

So the effect of increasing heart rate then would be because of progesterone, and the DMSO would then counteract the effect of progesterone in increasing the heart rate.

That is how I'm understanding it.
 

Wagner83

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It says it can change rhythm too. No sure why progesterone would give you arrythmia and very fast heart rate, sounds unlikely but you should ask Ray.
 
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yerrag

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It says it can change rhythm too. No sure why progesterone would give you arrhythmia and very fast heart rate, sounds unlikely but you should ask Ray.
The progesterone increases the metabolism rate, and that is manifested in increased temperatures. With higher metabolism, there is increased use of oxygen. The sudden increase in demand for oxygen by the cells requires that the red blood cells keep up with its supply of oxygen to the cells. But, in a person that is hypothyroid, netabolism is not efficient and it produces lactic acid, instead of carbon dioxide. The shortage of carbon dioxide being supplied to the blood causes the blood to be low on carbon dioxide. This creates a condition called respiratory alkalosis. With oxygen supply supply unable to keep up with oxygen demand, the heart has to compensate by increasing its rate. The breathing rate also increases in a manner described as hyperventilation. Meanwhile, the balance of electrolytes is disturbed, with for example magnesium and potassium going outside the cells (sorry my grasp is tenuous at best here on these electrolytes, which includes sodium and calcium) instead of staying inside the cells. The cardiac cells are similarly affected, and it affects the way the heart is pumped, the pumping mechanism being regulated very much by electrical charges from the electrolyte ions. This is where the heart rhythm gets affected, and irregular heart rate, or arrhythmia results.

Ray Peat has explained this in a few articles and interviews. One of them is entitled "Heart and Hormones" in his raypeat.com website. A search on his site on the keyword "arrhythmia" will yield many hits. But I'm just condensing his ideas in the limited way I can. The action of excess progesterone on a hypothyroid person leading to arrhythmia is just my take on it, and not coming from Ray Peat.
 
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yerrag

yerrag

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The rat was having a heart rate of 164 with arrhythmia. I checked blood and urine tests, and it confirmed respiratory alkalosis. I asked the vet interns what they have available to resolve the respiratory alkalosis condition. They have nothing. They don't even have paper bags. This morning I had the rat on bag breathing for 1 hour, with an oximeter monitoring her SpO2, pulse. It was around the 45th minutes when the heart rate went down to the 80s, half the rate when I started. The rat''s breath rate also went down to 24, from around the 50s.

It was a desperation attempt, a Hail Mary it seemed, and it worked. I may still do more bag breathing, just in case the irregular heart rate condition is not yet resolved.

The rat cardiologist may not be needed anymore, and the dreaded pacemaker would have to find another host.

@co2islife I am sore holding the bag for an hour. Looking forward to getting my carbogenen devices soon.
Too much of a good thing can be bad. Today, I followed up with a half-hour of bag breathing. I thought 1 hour would be excessive. I was right about the 1 hour. But wrong about the half hour. The rat began to have difficulty breathing, and was quivering by the mouth. The hospital oxygen had to be reconnected for breathing, and this oxygen corrected the condition. This condition is respiratory acidosis, which was a surplus this time of carbon dioxide.

I was being cautious, and yet I could still overload despite the caution.
 
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yerrag

yerrag

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The rat was having a heart rate of 164 with arrhythmia. I checked blood and urine tests, and it confirmed respiratory alkalosis. I asked the vet interns what they have available to resolve the respiratory alkalosis condition. They have nothing. They don't even have paper bags. This morning I had the rat on bag breathing for 1 hour, with an oximeter monitoring her SpO2, pulse. It was around the 45th minutes when the heart rate went down to the 80s, half the rate when I started. The rat''s breath rate also went down to 24, from around the 50s.

It was a desperation attempt, a Hail Mary it seemed, and it worked. I may still do more bag breathing, just in case the irregular heart rate condition is not yet resolved.

The rat cardiologist may not be needed anymore, and the dreaded pacemaker would have to find another host.

@co2islife I am sore holding the bag for an hour. Looking forward to getting my carbogenen devices soon.
Too much of a good thing can be bad. Today, I followed up with a half-hour of bag breathing. I thought 1 hour would be excessive. I was right about the 1 hour. But wrong about the half hour. The rat began to have difficulty breathing, and was quivering by the mouth. The hospital oxygen had to be reconnected for breathing, and this oxygen corrected the condition. This condition is respiratory acidosis, which was a surplus this time of carbon dioxide.

I was being cautious, and yet I could still overload despite the caution.
 

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As rats are wild here, I only keep guinea pigs... :)
I'd be curious to see how you would do with something like Progest-E (no dmso, vitamin E is solvent).
cleardot.gif
Do you mean the effect on hte heart was from DMSO?

I was being cautious, and yet I could still overload despite the caution.
For any breathing exercise, you have to check out that you do not overdo by taking the pulse. That is to say, increase CO2 what is needed to relax but not to the point of the reverse, stress.

Hope all get better for the rat!
 
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yerrag

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For any breathing exercise, you have to check out that you do not overdo by taking the pulse. That is to say, increase CO2 what is needed to relax but not to the point of the reverse, stress.

Hope all get better for the rat!
I had the oximeter to check the pulse while I was administering bag breathing. It was an hour after the bag breathing that something wrong occurred. The delayed reaction makes it difficult. I now would lessen bag breathing to 5 minutes each time, and do more of it instead, with maybe 15-30 minutes in between sessions.

I used this approach and it worked well. So well in fact, that I am surprised myself. Today, the arrhythmia is gone. I think the body slowly recovered with the help of bag breathing (in restoring CO2 to the blood), and eventually the electrolyte balance was restored, and slowly the expression of arrhythmia was reduced until it was no longer there.

Rat now has a regular heart beat. Heart rate has stabilized at around 80, which is much higher than it used to be. Temperature is at 37.1 It seems there is still some effect left from the progesterone from 5 days ago.

Rat had not eaten for 3 days, but has began to take some liquid food, but has been on dextrose to keep sugar levels stable and supportive. Vets advise tube feeding, but I declined as I felt feeding and the digestive process would interfere with the healing process. I also have to wonder whether such advices are really meant more to protect the vets from recrimination than to help patient recover. It is counter-intuitive to not rush to feed during the early stage of recovery, and usually conventional wisdom prevails. There is no way to tell if feeding at any early stage really helped speed up recovery. There is no parallel universe to compare with.
 
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schultz

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Ray always mentions that progesterone can cause the thyroid to release extra thyroid hormone in response to a sudden increase in progesterone.

"... estrogen can reach the point at which it starts inhibiting the thyroid gland itself. The thyroid gland, to produce the proper ratio of three parts T4 to one part of T3, it does that by breaking down the thyroglobulin, a colloidal kind of glob of protein inside the follicles of the gland. T his has to be digested as needed, breaking each protein molecule down and releasing these free thyroxin and T3 hormones. And estrogen inhibits the proteolytic enzyme that releases the hormone. So, first, it slows down liver function, but then it reaches a point where it will even block the thyroid itself. And this is where women tend to have a high frequency of goiter, thyroid enlargement. They call it Hashimoto’s thyroiditis, but most often it's what they used to call a colloid goiter, where, since estrogen stimulates the stress hormones in the brain, increasing thyroid stimulating hormone, estrogen causes the pituitary to drive the thyroid harder, meanwhile it's blocking the ability of the thyroid gland to secrete it, so it tends to enlarge the thyroid, and, then they get diagnosed as having thyroiditis. Progesterone happens to activate these proteins that allow the thyroid to secrete, so I advise women who have an enlarged thyroid not to take progesterone until they've taken care of the enlargement of the thyroid. Because progesterone will normalize the proteins so fast that sometimes they will go into a slightly hyperthyroid state for a few weeks."
 
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yerrag

yerrag

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Ray always mentions that progesterone can cause the thyroid to release extra thyroid hormone in response to a sudden increase in progesterone.

"... estrogen can reach the point at which it starts inhibiting the thyroid gland itself. The thyroid gland, to produce the proper ratio of three parts T4 to one part of T3, it does that by breaking down the thyroglobulin, a colloidal kind of glob of protein inside the follicles of the gland. T his has to be digested as needed, breaking each protein molecule down and releasing these free thyroxin and T3 hormones. And estrogen inhibits the proteolytic enzyme that releases the hormone. So, first, it slows down liver function, but then it reaches a point where it will even block the thyroid itself. And this is where women tend to have a high frequency of goiter, thyroid enlargement. They call it Hashimoto’s thyroiditis, but most often it's what they used to call a colloid goiter, where, since estrogen stimulates the stress hormones in the brain, increasing thyroid stimulating hormone, estrogen causes the pituitary to drive the thyroid harder, meanwhile it's blocking the ability of the thyroid gland to secrete it, so it tends to enlarge the thyroid, and, then they get diagnosed as having thyroiditis. Progesterone happens to activate these proteins that allow the thyroid to secrete, so I advise women who have an enlarged thyroid not to take progesterone until they've taken care of the enlargement of the thyroid. Because progesterone will normalize the proteins so fast that sometimes they will go into a slightly hyperthyroid state for a few weeks."
I just listened to this interview and it's still fresh on my mind. Do you know what Ray means by "progesterone normalizing the proteins?" What protein is he referring to?
 

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I just listened to this interview and it's still fresh on my mind. Do you know what Ray means by "progesterone normalizing the proteins?" What protein is he referring to?

I think he means a reduction in the thyroid size. So the protein in the thyroid gland? Now that you've pointed it out it does seem a little funny.
 

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Thanks for sharing. I've had apprehensions about progesterone but had never heard anything like this until now. In fact the only bad thing I had heard of was exacerbation of symptoms for men with PFS. I knew I was being a bit reckless with my experimentation, and luckily aside from the PFS issues I've had nothing but positive effects from progesterone.

I gave about 7mg worth of progest-E to my grandma and her response was a slight positive effect on mood. I'd like to give her more because she's had cancer and strokes. And she's in her 80's. Maybe I'll have her talk to her doctor about it.
 
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yerrag

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I think he means a reduction in the thyroid size. So the protein in the thyroid gland? Now that you've pointed it out it does seem a little funny.
Reading over again and again, I think he's referring to the proteins that either regulate or produce the thyroid in the thyroid gland. With the enlarged thyroid, the estrogen is blocking the secretion of the thyroid by having a limiting effect on these proteins, even with the gland being directed to produce plenty of thyroid with the high TSH. When progesterone is used and it antagonizes the estrogen, suddenly these proteins are free to produce thyroid, and they end up producing too much of it, leading to hyperthyroid conditions.

Thanks for sharing. I've had apprehensions about progesterone but had never heard anything like this until now. In fact the only bad thing I had heard of was exacerbation of symptoms for men with PFS. I knew I was being a bit reckless with my experimentation, and luckily aside from the PFS issues I've had nothing but positive effects from progesterone.

I gave about 7mg worth of progest-E to my grandma and her response was a slight positive effect on mood. I'd like to give her more because she's had cancer and strokes. And she's in her 80's. Maybe I'll have her talk to her doctor about it.
I haven't used Progest-E, but Progestene is very strong and an equivalent amount of Progestene applied (7mg) might have a stronger effect. Could be too strong. That's why it's always good to start out with small quantities and observe. Erring on the side of caution is a much better way to go. And needs a patient approach imho.
 

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