“Anti Estrogens” Are Estrogenic

[ecstatichamster]

I was listening to Dr. Peat and he mentioned that tamoxifen and similar “anti estrogens” have estrogenic effects.

Sure enough of course, he’s right.

Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens.
We find that tamoxifen is a potent activator of estrogen receptor (ER)- mediated induction of promoters regulated by AP-1 sites including the human collagenase gene promoter and constructs in which an AP-1 site is fused to the herpes thymidine kinase promoter. This contrasts with the inability of tamoxifen to activate otherwise identical promoters bearing classical estrogen response elements. Tamoxifen agonism at AP-1 sites is cell type specific, occurring in cell lines of uterine, but not of breast, origin. It thus parallels tamoxifen agonism in vivo. AP-1 proteins such as Jun or Jun/Fos are needed for tamoxifen stimulation, and tamoxifen increases the transcriptional efficiency of these proteins even when they are provided at optimal amounts. The DNA binding domain (DBD) of ER is required for tamoxifen activation at AP-1 sites. In contrast, estrogen activation is partially independent of this domain. This suggests the existence of two pathways of ER action at AP-1: an alpha (DBD-dependent) pathway activated by tamoxifen, and a beta (DBD-independent) pathway activated by estrogen. Fusing VP16 transcriptional activation functions to ER potentiates the beta, but not the alpha, pathway. We discuss models for the two pathways and the possibility that the AP-1 pathway is a major route by which ER affects target tissue growth and differentiation in vivo.

 

[ecstatichamster]

I have never heard Dr. Peat suggest any good long term effects of the estrogen inhibitors either, by the way.

 

[charlie]

 

[rei]

It is amazing how little actual science is in studies that are used to justify the sale of some drug. I bet even highschool science students could point out the errors in the "studies" drug companies put out to justify licensing of their new super drug.

 

[schultz]

I remember him talking about this. I think he was specifically referring to SERMs, and not the AI type drugs. But for all we know, AI type drugs might have estrogenic effects as well or some other weird action. We just don't know, which is why researchers shouldn't use these to demonstrate the effects of "low estrogen", something which I find highly irritating. All it demonstrates, at this point, is the effect of an AI. If an AI causes liver problems, that would be an estrogenic effect IMO. You wouldn't conclude that low estrogen causes liver problems.

 

[ecstatichamster]

he mentions tamoxifen in the interview.

 

[haidut]

I was listening to Dr. Peat and he mentioned that tamoxifen and similar “anti estrogens” have estrogenic effects.

Sure enough of course, he’s right.

Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens.
We find that tamoxifen is a potent activator of estrogen receptor (ER)- mediated induction of promoters regulated by AP-1 sites including the human collagenase gene promoter and constructs in which an AP-1 site is fused to the herpes thymidine kinase promoter. This contrasts with the inability of tamoxifen to activate otherwise identical promoters bearing classical estrogen response elements. Tamoxifen agonism at AP-1 sites is cell type specific, occurring in cell lines of uterine, but not of breast, origin. It thus parallels tamoxifen agonism in vivo. AP-1 proteins such as Jun or Jun/Fos are needed for tamoxifen stimulation, and tamoxifen increases the transcriptional efficiency of these proteins even when they are provided at optimal amounts. The DNA binding domain (DBD) of ER is required for tamoxifen activation at AP-1 sites. In contrast, estrogen activation is partially independent of this domain. This suggests the existence of two pathways of ER action at AP-1: an alpha (DBD-dependent) pathway activated by tamoxifen, and a beta (DBD-independent) pathway activated by estrogen. Fusing VP16 transcriptional activation functions to ER potentiates the beta, but not the alpha, pathway. We discuss models for the two pathways and the possibility that the AP-1 pathway is a major route by which ER affects target tissue growth and differentiation in vivo.

It is not just tamoxifen, there is also Clomifene (Clomid), Raloxifene, Toremifene, Lasofoxifene, Ormeloxifene, Ospemifene, Bazedoxifene, Anordrin, Broparestrol, Cyclofenil, etc. ALL of these are basically synthetic estrogens, just look at the molecular structure. They just happen to have somewhat antiestrogenic effects in some specific tissue but their systemic effects are still quite estrogenic.
Aspirin, brain, and cancer
"...Recently, the public has been led to believe that drugs are being designed to fit certain cellular "receptors." The history of the "COX-2 inhibitors" is instructive, in a perverse way. The structures of DES and other synthetic estrogens were said to relate to "the estrogen receptor." Making these estrogenic molecules more soluble in water made them somewhat anti-estrogenic, leading to products such as Tamoxifen. But some of the molecules in this group were found to be antiinflammatory. The structure of Celecoxib and other "COX-2 inhibitors" is remarkably similar to the "designer estrogens." Considering this, it's a little odd that so few in the U.S. are openly discussing the possibility that estrogen's function is directly related to inflammation, and involves the production of many inflammatory mediators, including COX-2. (See Lerner, et al., 1975; Luo, et al., 2001; Cushman, et al, 2001; Wu, et al., 2000; Herrington, et al., 2001.)"

He also mentions in the quote above the COX-2 inhibitors, of which the most (in)famous one is Vioxx. It killed quite a few people while still in clinical trials.
Rofecoxib - Wikipedia

Most of the *coxib drugs are stilbene/stilbenoid derivatives - known and potently estrogenic molecules, which are very common in nature.
Stilbenoid - Wikipedia
The most prominent and most heavily marketed stilbenoid is resveratrol. So, the next time somebody tries to explain to you how resveratrol is a "natural SERM" you can quietly laugh (or cry) inside.

 

[ShotTrue]

he mentions tamoxifen in the interview.

tamoxifen is a SERM. Selective Estrogen Receptor Modulator. These block endogenous estrogen action at the nipples, I believe, while being known to affect the mind and bones estrogenically.

AIs, aromatase inhbitors, either bind or destroy the aromatase enzymes, thus preventing testosterone's conversion into estrogen. These would be exemestane, letrozole, arimidex.
AIs are known to increase test by preventing its conversion to estrogen, and what is usually known to lower estrogen too much

 

[ilikecats]

@haidut lol “quite a few.” Haidut: big pharma apologist. Just joking, but yeah it’s been recognized by people within the FDA as causing 50,000 deaths and that’s the number the FDA is actually owning up to! Imagine what the number actually is. Yeah they frauded their clinical trials (didnt you post something on that?) and it was on the market for quite awhile before being pulled. I remember reading a headline in the past year that some pharma company was considering bringing it back! Wtf

“as many as 55,000 patients may have died from heart attacks and strokes induced by the drug, according to estimates by drug safety officials at the F.D.A.”- New York Times

Here it is:

“In November 2017, Massachusetts-based Tremeau Pharmaceuticals announced its plan to return rofecoxib (TRM-201) to market as a treatment for hemophilic arthropathy (HA). Tremeau announced that the FDA had granted an orphan designation for TRM-201 (rofecoxib) for the treatment of HA, and that they had received FDA feedback on their development plan.[7] HA is a degenerative joint disease caused by recurrent intra-articular bleeding. It is the largest cause of morbidity in patients with hemophilia and has no currently approved treatment options in the United States. Traditional NSAIDs are avoided in this population due to their effects on platelet aggregation and risk of gastrointestinal ulcers,[8] and high potency opioids are the current standard of care in treating HA.[9]”

 

[RisingSun]

I was listening to Dr. Peat and he mentioned that tamoxifen and similar “anti estrogens” have estrogenic effects.

Sure enough of course, he’s right.

Tamoxifen activation of the estrogen receptor/AP-1 pathway: potential origin for the cell-specific estrogen-like effects of antiestrogens.
We find that tamoxifen is a potent activator of estrogen receptor (ER)- mediated induction of promoters regulated by AP-1 sites including the human collagenase gene promoter and constructs in which an AP-1 site is fused to the herpes thymidine kinase promoter. This contrasts with the inability of tamoxifen to activate otherwise identical promoters bearing classical estrogen response elements. Tamoxifen agonism at AP-1 sites is cell type specific, occurring in cell lines of uterine, but not of breast, origin. It thus parallels tamoxifen agonism in vivo. AP-1 proteins such as Jun or Jun/Fos are needed for tamoxifen stimulation, and tamoxifen increases the transcriptional efficiency of these proteins even when they are provided at optimal amounts. The DNA binding domain (DBD) of ER is required for tamoxifen activation at AP-1 sites. In contrast, estrogen activation is partially independent of this domain. This suggests the existence of two pathways of ER action at AP-1: an alpha (DBD-dependent) pathway activated by tamoxifen, and a beta (DBD-independent) pathway activated by estrogen. Fusing VP16 transcriptional activation functions to ER potentiates the beta, but not the alpha, pathway. We discuss models for the two pathways and the possibility that the AP-1 pathway is a major route by which ER affects target tissue growth and differentiation in vivo.

The examples of "anti estrogens" you are giving are actually Selective Estrogen Receptor Modulators.

They do exert estrogenic activity in some tissues, and anti estrogenic activities in other tissues.

I would designate by anti estrogens the class of drugs called Aromatase Inhibitors, to which pertains Exemestane and Letrozole among many others. These have absolutely zero estrogenic activity.

 

[rei]

So the "too low estrogen" symptoms "known" in bodybuilding communities are actually effects of estrogen and especially the unbalanced signalling. Big surprise.

 

[Goobz]

Yeah as above, Tamoxifen isn't an anti estrogen, it's a SERM. Thus, the estrogenic and anti estrogenic actions of Tamoxifen you are describing are exactly what that particular drug supposed to do - selectively modulate the estrogen receptor. I.e. block receptors in certain locations (in the breast, for cancer) and activate receptors in other locations.

 

[ecstatichamster]

The examples of "anti estrogens" you are giving are actually Selective Estrogen Receptor Modulators.

They do exert estrogenic activity in some tissues, and anti estrogenic activities in other tissues.

I would designate by anti estrogens the class of drugs called Aromatase Inhibitors, to which pertains Exemestane and Letrozole among many others. These have absolutely zero estrogenic activity.

I am not disagreeing with you, with all respect, but I want to point out that this is a drug company line that you are giving us here.

They did not design these to do it. It’s just how it works, and it is taken and given to lower estrogen levels.

Reminds me of their propaganda by calling the other types of drugs SSRIs, it’s just a made-up mechanism.

 

[ShotTrue]

So the "too low estrogen" symptoms "known" in bodybuilding communities are actually effects of estrogen and especially the unbalanced signalling. Big surprise.

No you're completely wrong. Bodybuilders don't use serms during cycle typically AIs

 

[ShotTrue]

I am not disagreeing with you, with all respect, but I want to point out that this is a drug company line that you are giving us here.

They did not design these to do it. It’s just how it works, and it is taken and given to lower estrogen levels.

Reminds me of their propaganda by calling the other types of drugs SSRIs, it’s just a made-up mechanism.

It's taken to block estrogen from binding in the breast, which it does well if anecdotal accounts of treating gyno in 100s of cases in can believed.
Frankly I hated SERMS mental effects I would avoid them at all cost

 

[ShotTrue]

This whole thread seems like confusing SERMS with AIs.

 

[Goobz]

Both SERMs and AIs cause cognitive decline. Estradiol / aromatase is critical to the function of hormones such as pregnenolone and DHEA in the brain, and just critical to the brain in general.

Neuroprotection by the steroids pregnenolone and dehydroepiandrosterone is mediated by the enzyme aromatase
"The administration of the aromatase inhibitor fadrozole blocked the neuroprotective effect of pregnenolone and DHEA."
Neuroprotection by the steroids pregnenolone and dehydroepiandrosterone is mediated by the enzyme aromatase. - PubMed - NCBI

 

[ShotTrue]

Thank you for the link @Goobz . Having too low estradiol feels awful and impairs mood and cognitive functioning.

 

[Tarmander]

Calcium D-glucarate? DIM?

 

[TheBeard]

Forget about SERMs and AI alltogether, they are overall more detrimental than beneficial no matter what your goal is.

I would use low dose transdermal DHT to deplete estrone from tissues, which is what really matters.
E2 serum levels are a poor indicator of your estrogenic activity, and AI will only ever rid you of aromatase and thus serum e2, they won’t deplete your tissue estrone.