TubZy Log (cured)

[TubZy]

Wanted to share this with you guys since I came across this the other day.

Fin gave me an inguinal hernia. I got a hernia after about a year on fin and had surgery for it (~12 years ago). I just seen this study come out this year regarding how certain anti estrogen drugs that target ERa can literally reverse severe inguinal hernia back to normal in mice.

They used the drug Fulvestrant which is a selective estrogen receptor degrader (SERD) and particularly target estrogen receptor alpha. This is a bit different than standard anti aromatase drugs which just inhibit the enzyme.

Now I wanted to post this because I think this drug Fulvestrant might have use for PFS as it acts differently than standard anti estrogenic compounds as it specifically targets ERa. Interestingly enough, the second study also shows that raloxifene works similar too. Another tie in is that estrogen receptor alpha signaling plays a large role in wound healing and when I had pfs along with many others wound healing was absolute shit.

Drug reverses groin hernias in male mice without surgery, shows promise in humans

Using a novel, medication-based approach, a new Northwestern Medicine study successfully reversed existing inguinal hernias in male mice and fully restored their normal anatomy without surgery.

news.northwestern.edu

Inhibition of Estrogen Signaling Reverses Established Inguinal Hernias - PMC

Background: An inguinal hernia occurs when an intestinal loop or fat pushes through a weak spot in the lower abdominal muscle (LAM), causing a painful bulge that has the potential to cause bowel obstruction. Despite a high prevalence in men (~25%), ...

pmc.ncbi.nlm.nih.gov

Shift from androgen to estrogen action causes abdominal muscle fibrosis, atrophy, and inguinal hernia in a transgenic male mouse model - PMC

Inguinal hernia is one of the most common disorders that affect elderly men. A major pathology underlying inguinal hernia is the fibrosis and other degenerative changes that affect the lower abdominal muscle strength adjacent to the inguinal canal. ...

pmc.ncbi.nlm.nih.gov

 

[zancek0]

1/2

Interesting find.

Let me share some of my thoughts. Mostly unrelated to these specific studies you shared. This is gonna be a longer post. (I had to cut it in 2 parts.)

In my opinion, from the POV of hormone-based approaches (that I don't really like), estrogen is the most annoyingly complex part of the puzzle of these weird syndromes.

Meso (one of the main PSSD researchers who's recently passed away) around 5-6 years ago thought that PSSD (and PFS etc.) is basically "silenced ERa". 0 dick sensitivity and 0 sexual pleasure meant very impaired ERa signalling ("epigenetically silenced"). Lack of mental libido (sexual aggression) and erection issues meant AR signalling issues. Why does the body have issues getting back to normalcy? Because estrogen signalling positively regulates epigenetic "de-silencing". He was clear that in theory it is possible to reverse this without the use of exogenous E2 (and he specifically mentioned valproic acid and lithium combined with specific TRT interventions, even MENT etc.).
Some people (like stereo on PSSD research discord server) think that PSSD is hyperestrogenism and that ERs (and some other nuclear receptors) are basically overly sensitive. On the surface it would seem this is totally opposed to Meso's theory. Both theories might be describing the same "hormonal state".

The current dominant perspective sees these issues in the following way. Receptors can "learn" to signal without ligands, only with chaperones (as in androgen deprivation therapies). The "cure" in such cases would be to introduce big doses of hormones so that the body now would think "Ah, since there's so many ligands, I can now afford to reverse the current adaptation". Oversaturation with ligands can lead to corresponding receptor downregulation/"silencing". In such cases "removal" of ligands would lead the body to think "Aaa, since there's no more ligands, I must remove the "silencing".
Who knows how well this describes what is actually going on. Would fulvestrant work in both of these cases (if we're talking about ER up/downregulation)? I don't know anyone that tried it.


Any theory based on androgens/estrogens and their receptors is very simplistic but does capture some of what is going on.
Gbold explicitly said that imbalance of ERa/ERb ratio is at the center of all these syndromes. HOWEVER, the trick is that in his view ALL chronic conditions are characterized by ERa/ERb imbalances.
Why? Because in his view, ERs effectively regulate copper transportation. The dominance of specific ER (alpha or beta) signalling depends on how much copper-based activity the body can afford and needs. He said shit like:

• copper retention is done by ERa; ERb stops copper retention... which means: when you have a lot of copper in the body, ERb gets upregulated which downregulates ERa signalling (since ERb negatively regulates ERa; meaning when body "wants" less estrogen-based activity, eg. wants less tissue growth, it upregulates ERb);
• in slow metabolism ERa is downregulated; taking copper in slow metabolism further downregulates ERa by upregulating ERb (body does not want tcopper in slow metabolism);
• fast oxidizers can "afford" more ERa because they need more ERa for SODs; taking T3 (increasing metabolic rate) "opens up" ERa etc. etc. etc.

So in his opinion, generally speaking, slow metabolism = low ERa/ERb ratio; fast metabolism = high ERa/ERb ratio. Fast oxidizer = bioavailable copper (is in constant need of copper); slow metabolizer = no bioavailable copper (has too much copper but not utilized). (Well, Gbold did say that adult fast oxidizers are fake fast oxidizers ... Most "toxic" heavy metals are also metalloestrogens. Mercury etc. all bind to ERs. Copper does too, of course, but this is "correct" so to speak. Maybe copper amplifies E2 signalling whereas mercury etc. does the opposite...)

Fast oxidizer taking an aromatase inhibitor would so to speak remove his "defense" against ROS which would prompt the body to make ERa even more sensitive. This wouldn't happen to such an extent in a slow metabolizer; but since the slow metabolizer already operates with lower ERa, the sudden burst in estrogens at withdrawal would downregulate ERa even more. Gbold's proposed protocol to gain back ERa signalling was "TRT + T3 + dexamethasone". To downregulate ERa in a fast oxidizer, one would have to take more copper (and possibly also calcium as is often prescribed in HTMA to slow down metabolism).
Gbold said: slow metabolizers are copper toxic. A fast oxidizer can become slow with too much copper and remain slow because of too much copper.

What does exogenous estradiol do? According to Gbold, exogenous hormones excrete corresponding minerals. Taking E2 from outside would excrete copper in this view (body basically saying: "wait, we are getting insane amounts of estrogen so we have to get rid of copper to avoid too much estrogen signalling). The problem is that E2 messes with bile flow. And copper is excreted via bile. So it ain't that simple. I think Ray Peat was correct in saying that estrogens are the most energetically demanding molecules for the liver to metabolize. Men shouldn't be playing with estrogen too much...

 

[zancek0]

2/2

ANYWAYYYYY,
I've been running a group for people experiencing long-term "low E2" symptoms (of course, this is based mostly on vibes) after various kinds of interventions directly affecting aromatase or ERa/ERb ratio (let's assume talking about such a ratio even makes "theoretical/conceptual" sense). Let's say we call this group "PAIS" (post aromatase inhibitor syndrome) since most of these people are those that got hurt by aromatase inhibitors (but there's also people with long-term low E2 symptoms after tamoxifen, masteron, improperly handled TRT etc.). I've thus far met and talked to about 20 people (from different forums) that fit this description. My conclusion is that there's as much likeness (in terms of blood work, symptoms, background etc.) between cases as there is among PFS (and PSSD, PAS, lion's mane, ashwaganda, saw palmetto-syndrome etc.) cases. Meaning - it's not technically correct to say that it is a disease of its own (a totally unique imbalance). If we studied these syndromes long enough, we could find some underlying patterns (on hs Gbold and others often talked about "types" of PFS, PSSD etc.; Gbold even created protocols for 2 specific types). I did observe some patterns but, of course, nothing conclusive and, as I said, too much similarities to other syndromes.

I know PAMD cases that look like the kind of PFS where the person doesn't respond to any doses of androgens (even 5grams per week!). I know PAMD cases that cannot tolerate even 3mg of testosterone (they get all kinds of crazy symptoms; btw, I know someone with this intolerance that took 1 pill of raloxifene and this reversed this intolerance such that we was then able to tolerate "normal" doses of testosterone) but do not react significantly to 20mg of E2 injections (meaning they don't get any high E2 symptoms!). I know PAMD cases with 0 genital sensitivity, and PAMD cases with enhanced genital sensitivity. Those with dry mouth, those who hypersalivate; those who can't sleep vs those who could sleep anywhere. Etc. etc. Lack of/reduced energy and sexual symptoms (as I said, not necessarily negative) are the most common symptoms - but this also applies to PFS and other syndromes and conditions.

Still, a lot of these PAMD people were eager to try various forms of estradiol therapy (probably following Spyros' ideas). Pills, gels, injections. Various doses (from 10mcg to literally 20mg). (Personally, I reacted very poorly to 70mg of TRT/week + 50mcg of E2 enanthate/1x week (got it custom made by some MtF chemist lol). Hypothyroidism based on TSH (I know, high TSH isn't always indicative of hypothyroidism) and based on how I felt (slow as fuck, tired, nauseous but also had moments of euphoria)). About 6 people I spoke to actually reversed their syndrome with E2 therapy. It was interesting to see how some people reacted negatively or neutrally to certain E2 forms but benefited a lot by others. For example, it took 2 doses of E2 pills for someone to reverse this syndrome after suffering from it for 2 years. Most PAMD cases don't have such luck. For example, the case of Solothesensei: E2 pills AND E2 valerate injections had no significant effect (some positives). Interestingly, E2 cypionate (in MCT) totally reversed his syndrome permanently (search solothesensei on X - he's now promoting various combinations/doses of DHT enan/prop and E2 cyp for PFS and PAMD).


I'm gonna stop here. Good luck reading all that. ))

 

[Yura]

@zancek0 "According to Gbold, exogenous hormones excrete corresponding minerals. Taking E2 from outside would excrete copper in this view (body basically saying: "wait, we are getting insane amounts of estrogen so we have to get rid of copper to avoid too much estrogen signalling). The problem is that E2 messes with bile flow. And copper is excreted via bile. So it ain't that simple. "

Exacly.. Most females taking estrogen end up with cholestasis and later gallstones and later gallbladder removal. There is no copper elimination with bile happening..
Btw that is my issue. Post steroids, copper in the liver, low in the blood, low ceruloplasmin, crashed estrogen.. Wonder if I should try resveratrol.. For now I will try kick start bile production..

 

[zancek0]

@zancek0 "According to Gbold, exogenous hormones excrete corresponding minerals. Taking E2 from outside would excrete copper in this view (body basically saying: "wait, we are getting insane amounts of estrogen so we have to get rid of copper to avoid too much estrogen signalling). The problem is that E2 messes with bile flow. And copper is excreted via bile. So it ain't that simple. "

Exacly.. Most females taking estrogen end up with cholestasis and later gallstones and later gallbladder removal. There is no copper elimination with bile happening..
Btw that is my issue. Post steroids, copper in the liver, low in the blood, low ceruloplasmin, crashed estrogen.. Wonder if I should try resveratrol.. For now I will try kick start bile production..

Let's be careful. I think women get cholestasis not only because of estrogen but combination of estrogen and progestins. But yeah, I think you're right.
(Estrogen stimulates release of cholesterol into gallbladder and progesterone reduces gallbladder contraction = bile stagnation)

It's possible to make copper complexes that are excretable via urine (typical Wilson disease agents). Opiath also suggested histidine and carnosine to excrete copper via skin and urine also.


Go on low oxalate diet. I think oxalate accumulation is a problem for you. Oxalates block bile production. Check "trying low oxalates" group on FB.
Any hemolytic anemia in your case? Would also increase gallstones (bilirubin accumulation).

I'm not sure about resveratrol. It's a phenol which makes it a bit annoying in the context of a struggling liver and sulfation. Though maybe there are some herbs that might help you.
Check "kidney yang" in traditional chinese medicine. Kidney yang/yin roughly matches western conceptions regarding the function of estrogen.


Low oxalate diet, malic acid/magnesium malate, digestive bitters (need to touch the tongue to activate bitter receptors), lecithin, insoluble fiber. Might also need some calcium supplements. That might be a good start for bile flow.

 

[Yura]

@zancek0 I have basically all the blood markers of copper deficiency low white blood cells, low neutrophils, low estradiol.. But I had one time insanely high free copper which was probably copper dump.. bilirubin is ok. Liver enzymes elevated almost always. I don't consume a lot of oxalates. My only oxalates are from lets say 100g of oats, sometimes I hae buckwheat that is higher in oxalates, but my overal intake is lower. No nuts, seeds, spinach, potatoes any of that.. Yeah I started recently with liver flushes again so malic acid, I take lecithin as well. Artichoke and dandelion extract. I open the capsule and put it on my food.. Also garlic to kill pathogens.. But becaues I had great bile flow in croatia when I was working summer job there. I think my cholestasis is stress related as well. Don't feel good where I live my whole life. Stress from family etc.. But hard to move out when you can barely work par time etc.. Btw soluble fiber makes me worse I think for sure. When there is no bile soluble fiber just makes the transit time so much slower.. I would eat the bag of organic gluten free oats that I have here and I will no longer eat them.. For insoluble fiber I do green beans, brussell sprouts..
As I was writing in my blog. I will drop all supplements until I see my new hair test. I think taking copper antagonists makes everything just worse.. I will keep just the basic stuff like elecrolytes, little vit C, selenium, iodine, K2 and that's it.. Also I should probably do retinol serum test as I am already like 7 years on low vit A diet.. Was poisoning myself for a decade with high vit A foods before that.. Accutane low dose cycle as well etc.. I think that lowered zinc a lot due to high demand for RBP right?

 

[ruprmurdoch]

Wanted to share this with you guys since I came across this the other day.

Fin gave me an inguinal hernia. I got a hernia after about a year on fin and had surgery for it (~12 years ago). I just seen this study come out this year regarding how certain anti estrogen drugs that target ERa can literally reverse severe inguinal hernia back to normal in mice.

They used the drug Fulvestrant which is a selective estrogen receptor degrader (SERD) and particularly target estrogen receptor alpha. This is a bit different than standard anti aromatase drugs which just inhibit the enzyme.

Now I wanted to post this because I think this drug Fulvestrant might have use for PFS as it acts differently than standard anti estrogenic compounds as it specifically targets ERa. Interestingly enough, the second study also shows that raloxifene works similar too. Another tie in is that estrogen receptor alpha signaling plays a large role in wound healing and when I had pfs along with many others wound healing was absolute shit.

Drug reverses groin hernias in male mice without surgery, shows promise in humans

Using a novel, medication-based approach, a new Northwestern Medicine study successfully reversed existing inguinal hernias in male mice and fully restored their normal anatomy without surgery.

news.northwestern.edu

Inhibition of Estrogen Signaling Reverses Established Inguinal Hernias - PMC

Background: An inguinal hernia occurs when an intestinal loop or fat pushes through a weak spot in the lower abdominal muscle (LAM), causing a painful bulge that has the potential to cause bowel obstruction. Despite a high prevalence in men (~25%), ...

pmc.ncbi.nlm.nih.gov

Shift from androgen to estrogen action causes abdominal muscle fibrosis, atrophy, and inguinal hernia in a transgenic male mouse model - PMC

Inguinal hernia is one of the most common disorders that affect elderly men. A major pathology underlying inguinal hernia is the fibrosis and other degenerative changes that affect the lower abdominal muscle strength adjacent to the inguinal canal. ...

pmc.ncbi.nlm.nih.gov

zn/mn stack is anti estrogen, isn't it ?