“Anti Estrogens” Are Estrogenic

[ecstatichamster]

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.

1. What about progesterone?
2. What evidence do you have about DHT?

 

[BigChad]

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.

just wondering should grapes be avoided due to the resveratrol. I've heard grape seed extract is anti estrogenic, so maybe something is present in grapes that counteracts the resveratrol?
also not sure of the vitamin E tocotrienols and whether they are estrogenic or anti thyroid... while they are unsaturated, vitaminA is also unsaturated so I wonder if you simply need some vitamin C and vitamin E tocopherols to counteract the negative effects of vitamin A/tocotrienols being unsaturated

 

[BigChad]

@ecstatichamster these anti estrogen products seem to be built off a similar premise to phytoestrogens being argued as being "anti estrogens"? I remember some articles/people argue online that plant estrogens like soy products, if not too excessive, are actually anti estrogenic due to being less potent than mammalian estrogen and interfering with it

 

[NextLevel_]

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.

Let’s say you are doing a steroid cycle. Usually people do pct with AI‘s and/or Serms etc
You are saying they are both „bad“.
So what would be your pct then? Would you use low dose transdermal DHT (Androsterone??) instead? I don’t know if it would do further shoutdown after the cycle though.

 

[nbznj]

^HCG through the cycle and then as a stand-alone for a month or two and then Triptorelin. No need for imperfect drugs designed in the 60s when we’ve got much better solutions now

Also, the tin foil hat is strong in this thread...

 

[TheBeard]

^HCG through the cycle and then as a stand-alone for a month or two and then Triptorelin. No need for imperfect drugs designed in the 60s when we’ve got much better solutions now

Also, the tin foil hat is strong in this thread...

Both HCG and Triptorelin trigger a negative feedback loop at the HPTA level, so far from ideal if you goal is to recover.

Agreed that keeping the balls full during cycle is the most important, as they act like a diesel engine: if they haven't been stimulated during cycle and atrophy, they will take a long time to restart.
Whereas the pituitary is like a gas engine, it will restart much faster.

@NextLevel_ you best bet after cycle (while being on HCG on cycle as mentioned by @nbznj is a good idea) is to do an Exemestane only PCT.

It's the cleanest of all AIs, with the elegant function of destroying the aromatase enzyme instead of temporarily blocking it (which would cause an estrogen rebound), and will stimulate the HPTA.

Don't ever, ever, ever touch Clomid, you will become an emotional mess

 

[NextLevel_]

Thank you @nbznj @TheBeard !

 

[bdawg]

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.

thoughts on this?

Third generation aromatase inhibitors (AI) have shown good clinical efficacy in comparison to the anti-estrogen tamoxifen. The steroidal AI, exemestane (EXE) has previously been shown to act as an androgen, but this report demonstrates the estrogen-like activity of EXE. Based on genome-wide microarray analysis, high correlation was seen between EXE-Only (EXE O, hormone-free) and hormone-containing AI-resistant lines. In addition, the top regulated genes in the EXE O lines were mostly estrogen-responsive genes. This estrogen-like activity of EXE was further validated using estrogen receptor (ER) activity assays, where in comparison to 17β-estradiol (E2), EXE was able to induce ER activity, though at a higher concentration. Also, this EXE-mediated ER activity was blocked by the ER antagonist ICI as well as the ERα-specific antagonist methyl-piperidino-pyrazole (MPP). Similarly, EXE was able to induce proliferation of breast cancer cell lines, MCF-7 and MCF-7aro, as well as activate transcription of known estrogen-responsive genes, i.e., PGR, pS2 and AREG. These results suggest that EXE does have weak estrogen-like activity.

Characterization of the weak estrogen receptor α agonistic activity of exemestane

 

[LucyL]

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.

According to this study, AI's (specifically letrazole) are effective at depleting tissue E1

Letrozole is superior to anastrozole in suppressing breast cancer tissue and plasma estrogen levels.
Letrozole suppressed pretreatment tumor levels of E(2), E(1), and E(1)S by 97.6%, 90.7%, and 90.1%, respectively.
...
Our data reveals that letrozole (2.5 mg o.d.) is more effective compared with anastrozole (1.0 mg o.d.) with respect to tissue as well as plasma estrogen suppression in patients with postmenopausal breast cancer.

 

[nbznj]

I could conceive that Triptorelin is optional if HCG was properly run throughout the cycle. There isn’t any issues with negative feedbacks from the decapeptide though, not true at all, at least at the doses used to stimulate the pituitary.

Aromasin is extremely risky in terms of quality of life. If the balls were kept functional while on cycle, clomid remains the superior since it will propel SHBG back up and be somewhat specific enough to trigger an hpta response. Whereas aromatase inhibition is a disaster overall, and e2 isn’t the only hormone to trigger negative feedback anyway.

AIs only are terrible for HRT and for PCTs, as seen in countless studies and bros experiments

 

[bdawg]

I could conceive that Triptorelin is optional if HCG was properly run throughout the cycle. There isn’t any issues with negative feedbacks from the decapeptide though, not true at all, at least at the doses used to stimulate the pituitary.

Aromasin is extremely risky in terms of quality of life. If the balls were kept functional while on cycle, clomid remains the superior since it will propel SHBG back up and be somewhat specific enough to trigger an hpta response. Whereas aromatase inhibition is a disaster overall, and e2 isn’t the only hormone to trigger negative feedback anyway.

AIs only are terrible for HRT and for PCTs, as seen in countless studies and bros experiments

again everyones different - ive been high estradiol all my life, stress, diet, low muscle mass (skinny fat growing up to high bf% now), genes - i get literally 0 sides from exe (touchwood)

i assume low estro people would get sides from having too low e2

 

[TheBeard]

again everyones different - ive been high estradiol all my life, stress, diet, low muscle mass (skinny fat growing up to high bf% now), genes - i get literally 0 sides from exe (touchwood)

i assume low estro people would get sides from having too low e2

Are you sure your exemestane is legit?

It would have an obese’s joints cracking in no time.

And by the way, not being able to put on muscle is not a high e2 sign, neither is being skinny fat.

 

[bdawg]

Are you sure your exemestane is legit?

It would have an obese’s joints cracking in no time.

And by the way, not being able to put on muscle is not a high e2 sign, neither is being skinny fat.

yep pfizer turkey version - no joint pain ever on androsterone, 11-kt or exe

and not the muscle issue per se but just that body fat increases the total aromatase enzyme so i guess i have more of it to lose?

 

[ilhanxx]

I made a huge mistake to use tamox. Ray peat and haidut was right. At the end of the story, tamox gave me 4kg more weight gain (abdominal fat), more e2 level and more stress. now I use pfizer legit exemestan 6.25 mg (1/4 tablet) , I can tolerate it for 3 days, any liver pain or joint pain, for now clouds has gone in my head. I will test dhea level also.

 

[Sospian]

According to this study, AI's (specifically letrazole) are effective at depleting tissue E1

Letrozole is superior to anastrozole in suppressing breast cancer tissue and plasma estrogen levels.
Letrozole suppressed pretreatment tumor levels of E(2), E(1), and E(1)S by 97.6%, 90.7%, and 90.1%, respectively.
...
Our data reveals that letrozole (2.5 mg o.d.) is more effective compared with anastrozole (1.0 mg o.d.) with respect to tissue as well as plasma estrogen suppression in patients with postmenopausal breast cancer.

I'm planning on using letrozole to nuke my Estrogen tissues and repair the varicocele that the doctors like to claim has "no impact at all".

 

[Goobz]

I'm planning on using letrozole to nuke my Estrogen tissues and repair the varicocele that the doctors like to claim has "no impact at all".

Just imo, but... don't do it. Using that very drug may be the single worst decision of my life. All my health problems began around that time.

I also have a varicocele. Letrozole did nothing to it. At a pretty high dose, too.

Do what you want, but imo AIs are horrible drugs. Breast cancer patients sometimes refuse to take them due to the crippling joint pain, brain and sleep problems, etc, and would rather risk death. They're pretty strongly linked with cognitive decline, in particular.

People who say otherwise on this forum are doing mental gymnastics to try to confirm their cognitive biases. The (growing) evidence simply doesn't support it. Take a closer look at the estrogen related studies posted in the science section of this website, and a theme emerges: over time, there are more and more replies of "wait a sec.. we can't conclude that... " or "no, the study didn't show that at all." In my opinion there's a reason many of Peat's ideas about estrogen never caught on, despite having emerged decades ago.

A recent study showed TRT vs TRT + AI, and the TRT + AI group had more visceral fat, worse bone health, poor libido, erection quality, etc.

Other hormonal options would be far better imo. Anything, basically. Well, maybe not extra cortisol or prednisone (great idea, Broda Barnes!)

 

[steel_reserve]

Fascinating thread. When I was on DIM I noticed that my chiropractic visits were significantly louder, but I didn't have joint pain.

I felt incredible but my heart started acting crazy even on small doses.

 

[GreekDemiGod]

So, gbolduev was right again with the whole contrarian endocrinology?

 

[ecstatichamster]

A recent study showed TRT vs TRT + AI, and the TRT + AI group had more visceral fat, worse bone health, poor libido, erection quality, etc.

cite please? Thanks.

 

[Sospian]

Just imo, but... don't do it. Using that very drug may be the single worst decision of my life. All my health problems began around that time.

I also have a varicocele. Letrozole did nothing to it. At a pretty high dose, too.

Do what you want, but imo AIs are horrible drugs. Breast cancer patients sometimes refuse to take them due to the crippling joint pain, brain and sleep problems, etc, and would rather risk death. They're pretty strongly linked with cognitive decline, in particular.

People who say otherwise on this forum are doing mental gymnastics to try to confirm their cognitive biases. The (growing) evidence simply doesn't support it. Take a closer look at the estrogen related studies posted in the science section of this website, and a theme emerges: over time, there are more and more replies of "wait a sec.. we can't conclude that... " or "no, the study didn't show that at all." In my opinion there's a reason many of Peat's ideas about estrogen never caught on, despite having emerged decades ago.

A recent study showed TRT vs TRT + AI, and the TRT + AI group had more visceral fat, worse bone health, poor libido, erection quality, etc.

Other hormonal options would be far better imo. Anything, basically. Well, maybe not extra cortisol or prednisone (great idea, Broda Barnes!)

I've taken AIs before including letrozole. The only thing I noticed was achy joints and no libido