Can you locally inhibit estrogen in your growth plates while leaving it intact in the rest of your body?

[7evenvox22]

Thread Song:

Spoiler: Song

Introduction:

Estrogen plays a paradoxical role in development. It’s one of the most important hormones for proper skeletal, neurological, and metabolic maturation, yet it’s also the single biggest factor responsible for growth plate closure. Globally suppressing estrogen through aromatase inhibitors can indeed prolong growth, but it comes at the cost of decreased bone quality, impaired brain development, and systemic dysfunction.

So, the real question is:
Can you selectively inhibit estrogen locally in the growth plates without touching it elsewhere?

Spoiler: Answer

Surprisingly, yes, there are multiple ways to modulate estrogenic activity at the tissue level without globally crashing E2.

The Case of Tamoxifen (Tamex):

Tamoxifen has long been studied as a selective estrogen receptor modulator (SERM), a compound that can act as an antagonist in some tissues and an agonist in others. However, its effects on bone and the growth plate are far more nuanced than people realize.

In the growth plate, Tamoxifen exhibits antagonistic properties, meaning it inhibits estrogen-mediated closure. Yet, paradoxically, it preserves or even promotes bone health in other tissues. This makes it a theoretically perfect candidate for localized modulation, at least on paper.

The issue?
Tamoxifen also lowers IGF-1 levels significantly and exhibits ambiguous estrogenic activity in other tissues, including the liver and brain. This systemic interference makes it suboptimal for precise growth modulation.

The Real Key: Tamoxifen’s Metabolites

Most people overlook the fact that Tamoxifen itself isn’t the true active compound responsible for these effects. Its metabolites are.

Among them, Endoxifen stands out. It binds to the estrogen receptor with over 100x the affinity of Tamoxifen itself, and its activity profile is much more selective. Another metabolite, Norendoxifen, has aromatase-inhibiting properties, but it’s Endoxifen that holds the most promise for targeted growth plate modulation.

ERα Modulation: The Core Mechanism

The estrogen receptor alpha (ERα) has two major activation domains:

- AF-1: Promotes bone formation and maintains bone health.
- AF-2: Drives growth plate maturation and closure.

For controlled linear growth, the goal is simple, inhibit AF-2 while keeping AF-1 active.

Endoxifen accomplishes exactly that. It selectively antagonizes AF-2 while leaving AF-1 intact. Even more impressively, it promotes ERα degradation and blocks non-genomic signaling cascades like PKC/SET, which further drive hypertrophy and closure.

This dual action means you’re effectively shutting down the molecular switch that closes the plate, while preserving the receptor functions responsible for bone quality and skeletal strength.

Why Endoxifen > Tamoxifen

- Higher ER Affinity: 100x stronger binding than Tamoxifen.
- Selective AF2 Antagonism: Inhibits closure while maintaining AF1-mediated bone integrity.
- Minimal IGF-1 Suppression: Much weaker hepatic ER signaling.
- Limited Central Activity: Reduced impact on neuroendocrine feedback.

Together, these make Endoxifen far more promising for local modulation of growth plates without the widespread drawbacks of full systemic estrogen blockade.

Metabolic Considerations: CYP26D & Enzymatic Variability

The enzyme CYP26D is primarily responsible for Endoxifen metabolism. Anything that inhibits this enzyme will drastically alter the ratio of Tamoxifen metabolites, which can completely shift how the drug behaves in the body.
This is critical because several commonly used compounds can inhibit CYP26D, unintentionally changing Endoxifen’s balance and potency. Furthermore, species differences (rat vs human) explain why preclinical results often conflict with human data. These enzymes function differently across species, leading to vastly different outcomes in growth plate modulation.



Summary:

- Estrogen drives growth plate closure primarily via ERα AF2 activation.
- Tamoxifen antagonizes this pathway, but its systemic ambiguity limits usefulness.
- Endoxifen, its dominant metabolite, selectively blocks AF2 while leaving AF1 active, maintaining bone integrity while delaying closure.
- CYP26D determines metabolite balance inhibition alters effects.
- Localized estrogen modulation is theoretically possible, and Endoxifen appears to be one of the most promising routes toward achieving it.



If you enjoyed this thread, bookmark it. I’ll be releasing a follow-up soon, diving deeper into how to exploit tissue-selective receptor modulators to fine-tune estrogenic signaling for skeletal development.

I apologize for my horrendous formatting. I seriously need someone to help me with it for my future threads.​

 

[Lovethekids😛]

No u cant

 

[Stacyslayerᛉ]

Cool Thread.

 

[Triax]

Good thread

 

[mewzilla]

i saw this on tiktok a couple days ago. pretty cool idea.

 

[Corpuscula]

Nice thread, but the question everyone is probably asking themselves now is WHY it isn’t used in any studies for height growth if it’s that much better than Aromasin

 

[7evenvox22]

Nice thread, but the question everyone is probably asking themselves now is WHY it isn’t used in any studies for height growth if it’s that much better than Aromasin

because it’s not something that’s easy to quantify in a study setting.
endoxifen works locally at the receptor, not by lowering systemic estrogen like aromasin does, so it doesn’t show up on standard bloodwork.
most researchers stick to aromatase inhibitors because they’re simple to track lower e2, measure igf-1, done.
endoxifen’s mechanism is receptor-level modulation, which needs tissue-specific analysis.
plus, no one’s funding growth-related studies with a breast cancer metabolite.
there’s no commercial incentive, even if it makes more sense mechanistically.

 

[Org3cel]

Thread Song:

Spoiler: Song

Introduction:

Estrogen plays a paradoxical role in development. It’s one of the most important hormones for proper skeletal, neurological, and metabolic maturation, yet it’s also the single biggest factor responsible for growth plate closure. Globally suppressing estrogen through aromatase inhibitors can indeed prolong growth, but it comes at the cost of decreased bone quality, impaired brain development, and systemic dysfunction.

View attachment 4326889



So, the real question is:
Can you selectively inhibit estrogen locally in the growth plates without touching it elsewhere?
View attachment 4326765

Spoiler: Answer

Surprisingly, yes, there are multiple ways to modulate estrogenic activity at the tissue level without globally crashing E2.

The Case of Tamoxifen (Tamex):

Tamoxifen has long been studied as a selective estrogen receptor modulator (SERM), a compound that can act as an antagonist in some tissues and an agonist in others. However, its effects on bone and the growth plate are far more nuanced than people realize.

In the growth plate, Tamoxifen exhibits antagonistic properties, meaning it inhibits estrogen-mediated closure. Yet, paradoxically, it preserves or even promotes bone health in other tissues. This makes it a theoretically perfect candidate for localized modulation, at least on paper.

View attachment 4326781

The issue?
Tamoxifen also lowers IGF-1 levels significantly and exhibits ambiguous estrogenic activity in other tissues, including the liver and brain. This systemic interference makes it suboptimal for precise growth modulation.

View attachment 4326787

The Real Key: Tamoxifen’s Metabolites

Most people overlook the fact that Tamoxifen itself isn’t the true active compound responsible for these effects. Its metabolites are.

Among them, Endoxifen stands out. It binds to the estrogen receptor with over 100x the affinity of Tamoxifen itself, and its activity profile is much more selective. Another metabolite, Norendoxifen, has aromatase-inhibiting properties, but it’s Endoxifen that holds the most promise for targeted growth plate modulation.

View attachment 4326795

ERα Modulation: The Core Mechanism

The estrogen receptor alpha (ERα) has two major activation domains:

- AF-1: Promotes bone formation and maintains bone health.
- AF-2: Drives growth plate maturation and closure.

For controlled linear growth, the goal is simple, inhibit AF-2 while keeping AF-1 active.

Endoxifen accomplishes exactly that. It selectively antagonizes AF-2 while leaving AF-1 intact. Even more impressively, it promotes ERα degradation and blocks non-genomic signaling cascades like PKC/SET, which further drive hypertrophy and closure.

This dual action means you’re effectively shutting down the molecular switch that closes the plate, while preserving the receptor functions responsible for bone quality and skeletal strength.

View attachment 4326857

Why Endoxifen > Tamoxifen

- Higher ER Affinity: 100x stronger binding than Tamoxifen.
- Selective AF2 Antagonism: Inhibits closure while maintaining AF1-mediated bone integrity.
- Minimal IGF-1 Suppression: Much weaker hepatic ER signaling.
- Limited Central Activity: Reduced impact on neuroendocrine feedback.

Together, these make Endoxifen far more promising for local modulation of growth plates without the widespread drawbacks of full systemic estrogen blockade.

View attachment 4326865

Metabolic Considerations: CYP26D & Enzymatic Variability

The enzyme CYP26D is primarily responsible for Endoxifen metabolism. Anything that inhibits this enzyme will drastically alter the ratio of Tamoxifen metabolites, which can completely shift how the drug behaves in the body.
This is critical because several commonly used compounds can inhibit CYP26D, unintentionally changing Endoxifen’s balance and potency. Furthermore, species differences (rat vs human) explain why preclinical results often conflict with human data. These enzymes function differently across species, leading to vastly different outcomes in growth plate modulation.



Summary:

- Estrogen drives growth plate closure primarily via ERα AF2 activation.
- Tamoxifen antagonizes this pathway, but its systemic ambiguity limits usefulness.
- Endoxifen, its dominant metabolite, selectively blocks AF2 while leaving AF1 active, maintaining bone integrity while delaying closure.
- CYP26D determines metabolite balance inhibition alters effects.
- Localized estrogen modulation is theoretically possible, and Endoxifen appears to be one of the most promising routes toward achieving it.



If you enjoyed this thread, bookmark it. I’ll be releasing a follow-up soon, diving deeper into how to exploit tissue-selective receptor modulators to fine-tune estrogenic signaling for skeletal development.

View attachment 4326893



I apologize for my horrendous formatting. I seriously need someone to help me with it for my future threads.​

Are there any studies done on this? Also how much endoxifen would one have to take to be as strong as 2.5mg of letrozole ED?
@MyDreamIsToBe183CM

 

[slaters]

@Bitchwhipper2

 

[Bitchwhipper2]

@Bitchwhipper2

Past my prime

 

[manletprofile]

w thread bhai

 

[Bitchwhipper2]

OP help me with intentions of limiting bloat while maintaining estrogens, skin, lipid and neuroprotection on cycle

 

[slaters]

Past my prime

That’s how I feel knowing I can get dht gel now

 

[Zagro]

Nice thread, @coolman985 you can also opt for this instead of endoxifen

 

[Outsidecel]

molecule found!!!

 

[7evenvox22]

OP help me with intentions of limiting bloat while maintaining estrogens, skin, lipid and neuroprotection on cycle

Sure, pm me ur stack.

 

[Org3cel]

OP help me with intentions of limiting bloat while maintaining estrogens, skin, lipid and neuroprotection on cycle

"How to make a cake whitout eggs, flour, sugar"

 

[Org3cel]

Thread Song:

Spoiler: Song

Introduction:

Estrogen plays a paradoxical role in development. It’s one of the most important hormones for proper skeletal, neurological, and metabolic maturation, yet it’s also the single biggest factor responsible for growth plate closure. Globally suppressing estrogen through aromatase inhibitors can indeed prolong growth, but it comes at the cost of decreased bone quality, impaired brain development, and systemic dysfunction.

View attachment 4326889



So, the real question is:
Can you selectively inhibit estrogen locally in the growth plates without touching it elsewhere?
View attachment 4326765

Spoiler: Answer

Surprisingly, yes, there are multiple ways to modulate estrogenic activity at the tissue level without globally crashing E2.

The Case of Tamoxifen (Tamex):

Tamoxifen has long been studied as a selective estrogen receptor modulator (SERM), a compound that can act as an antagonist in some tissues and an agonist in others. However, its effects on bone and the growth plate are far more nuanced than people realize.

In the growth plate, Tamoxifen exhibits antagonistic properties, meaning it inhibits estrogen-mediated closure. Yet, paradoxically, it preserves or even promotes bone health in other tissues. This makes it a theoretically perfect candidate for localized modulation, at least on paper.

View attachment 4326781

The issue?
Tamoxifen also lowers IGF-1 levels significantly and exhibits ambiguous estrogenic activity in other tissues, including the liver and brain. This systemic interference makes it suboptimal for precise growth modulation.

View attachment 4326787

The Real Key: Tamoxifen’s Metabolites

Most people overlook the fact that Tamoxifen itself isn’t the true active compound responsible for these effects. Its metabolites are.

Among them, Endoxifen stands out. It binds to the estrogen receptor with over 100x the affinity of Tamoxifen itself, and its activity profile is much more selective. Another metabolite, Norendoxifen, has aromatase-inhibiting properties, but it’s Endoxifen that holds the most promise for targeted growth plate modulation.

View attachment 4326795

ERα Modulation: The Core Mechanism

The estrogen receptor alpha (ERα) has two major activation domains:

- AF-1: Promotes bone formation and maintains bone health.
- AF-2: Drives growth plate maturation and closure.

For controlled linear growth, the goal is simple, inhibit AF-2 while keeping AF-1 active.

Endoxifen accomplishes exactly that. It selectively antagonizes AF-2 while leaving AF-1 intact. Even more impressively, it promotes ERα degradation and blocks non-genomic signaling cascades like PKC/SET, which further drive hypertrophy and closure.

This dual action means you’re effectively shutting down the molecular switch that closes the plate, while preserving the receptor functions responsible for bone quality and skeletal strength.

View attachment 4326857

Why Endoxifen > Tamoxifen

- Higher ER Affinity: 100x stronger binding than Tamoxifen.
- Selective AF2 Antagonism: Inhibits closure while maintaining AF1-mediated bone integrity.
- Minimal IGF-1 Suppression: Much weaker hepatic ER signaling.
- Limited Central Activity: Reduced impact on neuroendocrine feedback.

Together, these make Endoxifen far more promising for local modulation of growth plates without the widespread drawbacks of full systemic estrogen blockade.

View attachment 4326865

Metabolic Considerations: CYP26D & Enzymatic Variability

The enzyme CYP26D is primarily responsible for Endoxifen metabolism. Anything that inhibits this enzyme will drastically alter the ratio of Tamoxifen metabolites, which can completely shift how the drug behaves in the body.
This is critical because several commonly used compounds can inhibit CYP26D, unintentionally changing Endoxifen’s balance and potency. Furthermore, species differences (rat vs human) explain why preclinical results often conflict with human data. These enzymes function differently across species, leading to vastly different outcomes in growth plate modulation.



Summary:

- Estrogen drives growth plate closure primarily via ERα AF2 activation.
- Tamoxifen antagonizes this pathway, but its systemic ambiguity limits usefulness.
- Endoxifen, its dominant metabolite, selectively blocks AF2 while leaving AF1 active, maintaining bone integrity while delaying closure.
- CYP26D determines metabolite balance inhibition alters effects.
- Localized estrogen modulation is theoretically possible, and Endoxifen appears to be one of the most promising routes toward achieving it.



If you enjoyed this thread, bookmark it. I’ll be releasing a follow-up soon, diving deeper into how to exploit tissue-selective receptor modulators to fine-tune estrogenic signaling for skeletal development.

View attachment 4326893



I apologize for my horrendous formatting. I seriously need someone to help me with it for my future threads.​

@aids @chadisbeingmade @SlayerJonas
Have yall ever heard of this drug? It has over 400 studies on pubmed, Ill take a good look at it but seems promissing.

 

[neuf]

Thread Song:

Spoiler: Song

Introduction:

Estrogen plays a paradoxical role in development. It’s one of the most important hormones for proper skeletal, neurological, and metabolic maturation, yet it’s also the single biggest factor responsible for growth plate closure. Globally suppressing estrogen through aromatase inhibitors can indeed prolong growth, but it comes at the cost of decreased bone quality, impaired brain development, and systemic dysfunction.

View attachment 4326889



So, the real question is:
Can you selectively inhibit estrogen locally in the growth plates without touching it elsewhere?
View attachment 4326765

Spoiler: Answer

Surprisingly, yes, there are multiple ways to modulate estrogenic activity at the tissue level without globally crashing E2.

The Case of Tamoxifen (Tamex):

Tamoxifen has long been studied as a selective estrogen receptor modulator (SERM), a compound that can act as an antagonist in some tissues and an agonist in others. However, its effects on bone and the growth plate are far more nuanced than people realize.

In the growth plate, Tamoxifen exhibits antagonistic properties, meaning it inhibits estrogen-mediated closure. Yet, paradoxically, it preserves or even promotes bone health in other tissues. This makes it a theoretically perfect candidate for localized modulation, at least on paper.

View attachment 4326781

The issue?
Tamoxifen also lowers IGF-1 levels significantly and exhibits ambiguous estrogenic activity in other tissues, including the liver and brain. This systemic interference makes it suboptimal for precise growth modulation.

View attachment 4326787

The Real Key: Tamoxifen’s Metabolites

Most people overlook the fact that Tamoxifen itself isn’t the true active compound responsible for these effects. Its metabolites are.

Among them, Endoxifen stands out. It binds to the estrogen receptor with over 100x the affinity of Tamoxifen itself, and its activity profile is much more selective. Another metabolite, Norendoxifen, has aromatase-inhibiting properties, but it’s Endoxifen that holds the most promise for targeted growth plate modulation.

View attachment 4326795

ERα Modulation: The Core Mechanism

The estrogen receptor alpha (ERα) has two major activation domains:

- AF-1: Promotes bone formation and maintains bone health.
- AF-2: Drives growth plate maturation and closure.

For controlled linear growth, the goal is simple, inhibit AF-2 while keeping AF-1 active.

Endoxifen accomplishes exactly that. It selectively antagonizes AF-2 while leaving AF-1 intact. Even more impressively, it promotes ERα degradation and blocks non-genomic signaling cascades like PKC/SET, which further drive hypertrophy and closure.

This dual action means you’re effectively shutting down the molecular switch that closes the plate, while preserving the receptor functions responsible for bone quality and skeletal strength.

View attachment 4326857

Why Endoxifen > Tamoxifen

- Higher ER Affinity: 100x stronger binding than Tamoxifen.
- Selective AF2 Antagonism: Inhibits closure while maintaining AF1-mediated bone integrity.
- Minimal IGF-1 Suppression: Much weaker hepatic ER signaling.
- Limited Central Activity: Reduced impact on neuroendocrine feedback.

Together, these make Endoxifen far more promising for local modulation of growth plates without the widespread drawbacks of full systemic estrogen blockade.

View attachment 4326865

Metabolic Considerations: CYP26D & Enzymatic Variability

The enzyme CYP26D is primarily responsible for Endoxifen metabolism. Anything that inhibits this enzyme will drastically alter the ratio of Tamoxifen metabolites, which can completely shift how the drug behaves in the body.
This is critical because several commonly used compounds can inhibit CYP26D, unintentionally changing Endoxifen’s balance and potency. Furthermore, species differences (rat vs human) explain why preclinical results often conflict with human data. These enzymes function differently across species, leading to vastly different outcomes in growth plate modulation.



Summary:

- Estrogen drives growth plate closure primarily via ERα AF2 activation.
- Tamoxifen antagonizes this pathway, but its systemic ambiguity limits usefulness.
- Endoxifen, its dominant metabolite, selectively blocks AF2 while leaving AF1 active, maintaining bone integrity while delaying closure.
- CYP26D determines metabolite balance inhibition alters effects.
- Localized estrogen modulation is theoretically possible, and Endoxifen appears to be one of the most promising routes toward achieving it.



If you enjoyed this thread, bookmark it. I’ll be releasing a follow-up soon, diving deeper into how to exploit tissue-selective receptor modulators to fine-tune estrogenic signaling for skeletal development.

View attachment 4326893



I apologize for my horrendous formatting. I seriously need someone to help me with it for my future threads.​

What dosage and who the fuck sells this stuff

 

[@Tyov]

mirin the thread brah

 

[aids]

@aids @chadisbeingmade @SlayerJonas
Have yall ever heard of this drug? It has over 400 studies on pubmed, Ill take a good look at it but seems promissing.

Tamoxifen impairs both longitudinal and cortical bone growth in young male rats - PubMed

Tamoxifen (Tam) has been used experimentally to treat boys with gynecomastia and girls with McCune-Albright syndrome. This drug was recently shown to inhibit the growth of cultured fetal rat metatarsal bones and thus might also affect bone growth in vivo. Four-week-old Sprague-Dawley rats were...

pubmed.ncbi.nlm.nih.gov

You can extrapolate as much as you want from the mechanisms of a drug, but if it doesn't work in literature, it doesn't work.

 

[aids]

Tamoxifen impairs both longitudinal and cortical bone growth in young male rats - PubMed

Tamoxifen (Tam) has been used experimentally to treat boys with gynecomastia and girls with McCune-Albright syndrome. This drug was recently shown to inhibit the growth of cultured fetal rat metatarsal bones and thus might also affect bone growth in vivo. Four-week-old Sprague-Dawley rats were...

pubmed.ncbi.nlm.nih.gov

View attachment 4327373
You can extrapolate as much as you want from the mechanisms of a drug, but if it doesn't work in literature, it doesn't work.

Tamoxifen Improves Final Height Prediction in Girls with McCune-Albright Syndrome: A Long Follow-Up - PubMed

Our results support a role for tamoxifen in improving the FHP in patients with MAS.

pubmed.ncbi.nlm.nih.gov

Either way, results seem lacklustre compared to AI, ceteris paribus.
And this thread disregards that Tamoxifen can still have side effects regardless of whether you can maintain high serum E2 when using it.
@Org3cel

I still stand by non-steroidal AI, dosed appropriately, being most applicable for improving PAH.

 

[tomahawk]

Seems BoTB worthy

 

[Org3cel]

Tamoxifen Improves Final Height Prediction in Girls with McCune-Albright Syndrome: A Long Follow-Up - PubMed

Our results support a role for tamoxifen in improving the FHP in patients with MAS.

pubmed.ncbi.nlm.nih.gov

Either way, results seem lacklustre compared to AI, ceteris paribus.
And this thread disregards that Tamoxifen can still have side effects regardless of whether you can maintain high serum E2 when using it.
@Org3cel

I still stand by non-steroidal AI, dosed appropriately, being most applicable for improving PAH.

Btw Im starting to use pubmed as a good tool to research, what do I do when pubmed gives me 3 different results, Tamoxifen was said to:
National Institutes of Health (.gov) https://share.google/BOro3cH0jkFLrwrbq
Improve adult height
Not effect height (in the study u linked)
National Institutes of Health (.gov) https://share.google/TzjI89X6djcLnoCor
And no effect on height either positively or negatively haha
Like which of the 3 studies am I suppose to believe in?

 

[aids]

Btw Im starting to use pubmed as a good tool to research, what do I do when pubmed gives me 3 different results, Tamoxifen was said to:
National Institutes of Health (.gov) https://share.google/BOro3cH0jkFLrwrbq
Improve adult height
Not effect height (in the study u linked)
National Institutes of Health (.gov) https://share.google/TzjI89X6djcLnoCor
And no effect on height either positively or negatively haha
Like which of the 3 studies am I suppose to believe in?

There is almost always contradicting literature. You need to identify the nuance in each study to determine why the results were so different.
But the fact that the literature for Tamoxifen is so contradictory is what pushes me away.
You can safely use non-steroidal AI to push E2 to lower within RR and not affect cognitive development whatsoever (as indicated in the literature). As long as you dose responsibly and get frequent bloodwork, you will be ok.
Plus, non-steroidal AI is not progressive in its aromatase inhibition, compared to Aromasin that will be much harder to have an exact dosing for (as too little, too little, too much, and it's harder to reverse unless you dose bioidentical E2 until you have new aromatase enzymes made available as the existing ones were permanently shut down with a covalent bond).

 

[7evenvox22]

Tamoxifen impairs both longitudinal and cortical bone growth in young male rats - PubMed

Tamoxifen (Tam) has been used experimentally to treat boys with gynecomastia and girls with McCune-Albright syndrome. This drug was recently shown to inhibit the growth of cultured fetal rat metatarsal bones and thus might also affect bone growth in vivo. Four-week-old Sprague-Dawley rats were...

pubmed.ncbi.nlm.nih.gov

View attachment 4327373
You can extrapolate as much as you want from the mechanisms of a drug, but if it doesn't work in literature, it doesn't work.

if you actually read the thread (which you clearly didn’t) you’d see i was against tamoxifen from the start. the whole point was that tam impairs bone growth and plate closure, that’s why i focused on endoxifen. the rat data you’re posting literally proves that. tam lowers igf-1, slows longitudinal growth, and weakens cortical bone. that’s exactly why it’s a bad option for growth modulation. endoxifen’s the opposite. it raises bone density, keeps af-1 signaling active, and only blocks af-2, the domain responsible for closure. it doesn’t crash igf-1 or nuke systemic estrogen.
if you want sources, check:

Skeletal and Uterotrophic Effects of Endoxifen in Female Rats - PMC

Endoxifen, the primary active metabolite of tamoxifen, is currently being investigated as a novel endocrine therapy for the treatment of breast cancer. Tamoxifen is a selective estrogen receptor modulator that elicits potent anti–breast cancer ...

pmc.ncbi.nlm.nih.gov

A Proposed Therapeutic Role of (Z)-Endoxifen in Duchenne Muscular Dyst | DNND

Potential for new Duchenne Muscular Dystrophy therapy in the context of the overall DMD therapeutic landscape.

www.dovepress.com

Endoxifen, an Estrogen Receptor Targeted Therapy: From Bench to Bedside

mayoclinic.elsevierpure.com

The Effects of a Novel Hormonal Breast Cancer Therapy, Endoxifen, on the Mouse Skeleton - PMC

Endoxifen has recently been identified as the predominant active metabolite of tamoxifen and is currently being developed as a novel hormonal therapy for the treatment of endocrine sensitive breast cancer. Based on past studies in breast cancer ...

pmc.ncbi.nlm.nih.gov

so yeah, the study you linked doesn’t contradict anything, it actually backs up what i said.
but still, i appreciate you clearing up the misconception around tamoxifen. you’re a high iq user and posts like yours are why i bother writing these in the first place. i actually look up to how you break things down hope i can reach that level one day.

 

[neuf]

There is almost always contradicting literature. You need to identify the nuance in each study to determine why the results were so different.
But the fact that the literature for Tamoxifen is so contradictory is what pushes me away.
You can safely use non-steroidal AI to push E2 to lower within RR and not affect cognitive development whatsoever (as indicated in the literature). As long as you dose responsibly and get frequent bloodwork, you will be ok.
Plus, non-steroidal AI is not progressive in its aromatase inhibition, compared to Aromasin that will be much harder to have an exact dosing for (as too little, too little, too much, and it's harder to reverse unless you dose bioidentical E2 until you have new aromatase enzymes made available as the existing ones were permanently shut down with a covalent bond).

So, which AI would you recommend ? Anastrozole ?

 

[aids]

if you actually read the thread (which you clearly didn’t) you’d see i was against tamoxifen from the start. the whole point was that tam impairs bone growth and plate closure, that’s why i focused on endoxifen. the rat data you’re posting literally proves that. tam lowers igf-1, slows longitudinal growth, and weakens cortical bone. that’s exactly why it’s a bad option for growth modulation. endoxifen’s the opposite. it raises bone density, keeps af-1 signaling active, and only blocks af-2, the domain responsible for closure. it doesn’t crash igf-1 or nuke systemic estrogen.
if you want sources, check:

Skeletal and Uterotrophic Effects of Endoxifen in Female Rats - PMC

Endoxifen, the primary active metabolite of tamoxifen, is currently being investigated as a novel endocrine therapy for the treatment of breast cancer. Tamoxifen is a selective estrogen receptor modulator that elicits potent anti–breast cancer ...

pmc.ncbi.nlm.nih.gov

A Proposed Therapeutic Role of (Z)-Endoxifen in Duchenne Muscular Dyst | DNND

Potential for new Duchenne Muscular Dystrophy therapy in the context of the overall DMD therapeutic landscape.

www.dovepress.com

Endoxifen, an Estrogen Receptor Targeted Therapy: From Bench to Bedside

mayoclinic.elsevierpure.com

The Effects of a Novel Hormonal Breast Cancer Therapy, Endoxifen, on the Mouse Skeleton - PMC

Endoxifen has recently been identified as the predominant active metabolite of tamoxifen and is currently being developed as a novel hormonal therapy for the treatment of endocrine sensitive breast cancer. Based on past studies in breast cancer ...

pmc.ncbi.nlm.nih.gov

so yeah, the study you linked doesn’t contradict anything, it actually backs up what i said.
but still, i appreciate you clearing up the misconception around tamoxifen. you’re a high iq user and posts like yours are why i bother writing these in the first place. i actually look up to how you break things down hope i can reach that level one day.

Thanks for the end sentence.

I skimmed your thread but was referencing literature to Tamoxifen because there is far less than 400 results for "endoxifen" on PubMed, with over 3,000 for "tamoxifen" (obviously this is encompassing all literature, not specifically related to growth).

Now, regardless, I did read about the endoxifen and I have skimmed the literature you've sent here, but at the end of the day, this is all hypothetical based on extrapolation from the mechanisms of endoxifen.
I am not disagreeing with your research because I am less familiar about some of the things referenced in the thread and admittedly, don't really care too much to validate them, but as some others above have suggested, if Endoxifen was so superior in a height context, why is it not used?

It leads me to infer there is something (unintentionally) omitted from the thread that removes Endoxifen from researchers' consideration.
With that being said, could it be a perfect drug? Maybe, but these questions are not unfair to ask and any answer we might have is entirely speculative.

 

[aids]

So, which AI would you recommend ? Anastrozole ?

Any non-steroidal i.e., anastrazole or letrozole.

 

[coolman985]

Nice thread, @coolman985 you can also opt for this instead of endoxifen

Isn’t the thread about endoxifen?

 

[neuf]

Any non-steroidal i.e., anastrazole or letrozole.

Alright thank you, isn't letrozole the most violent out there for your mental health, i've heard a lot of testimonies about people literally being depressed even out there.

Btw, what dosage would you recommend for anastrazole?

 

[7evenvox22]

Thanks for the end sentence.

I skimmed your thread but was referencing literature to Tamoxifen because there is far less than 400 results for "endoxifen" on PubMed, with over 3,000 for "tamoxifen" (obviously this is encompassing all literature, not specifically related to growth).

Now, regardless, I did read about the endoxifen and I have skimmed the literature you've sent here, but at the end of the day, this is all hypothetical based on extrapolation from the mechanisms of endoxifen.
I am not disagreeing with your research because I am less familiar about some of the things referenced in the thread and admittedly, don't really care too much to validate them, but as some others above have suggested, if Endoxifen was so superior in a height context, why is it not used?

It leads me to infer there is something (unintentionally) omitted from the thread that removes Endoxifen from researchers' consideration.
With that being said, could it be a perfect drug? Maybe, but these questions are not unfair to ask and any answer we might have is entirely speculative.

appreciate the thoughtful reply man.
you're completely fair. tam’s had decades of research and clinical use so of course it’s gonna dominate the literature, endoxifen’s still in its early phase which is why most of what i wrote was theoretical.
the goal wasn’t to say it’s some proven miracle, just to outline how it could work better if anyone ever studied it for that use. most of what’s out there right now is oncology-focused, so all we can really do is extrapolate from mechanism and receptor behavior.
you’re right to question why it’s not used. It’s probably not even on the radar for growth research since it’s an active metabolite of an old drug with no patent value left. that doesn’t mean it wouldn’t work, just that no one’s incentivized to test it.
appreciate you taking the time to actually read through and give input.

 

[aids]

Alright thank you, isn't letrozole the most violent out there for your mental health, i've heard a lot of testimonies about people literally being depressed even out there.

Btw, what dosage would you recommend for anastrazole?

I wouldn't, start at the lowest and then taper up until you get to a reasonable E2 concentration that doesn't have any sides for your cogniscence.

 

[7evenvox22]

fuckkk i posted in the wrong section mods please move this to looksmaxing i can’t afford another thread flopping pls.
@SlayerJonas @chadisbeingmade @Gengar @TechnoBoss

thanks @chadisbeingmade seriously appreciate it.

 

[Zagro]

Isn’t the thread about endoxifen?

Yeah he lowk disses tamo i just skimmed through it, but tamo still is decent if you use hGH alongside

 

[coolman985]

Yeah he lowk disses tamo i just skimmed through it, but tamo still is decent if you use hGH alongside

Ahh I see but doesn’t one of tamoxifens metabolites mimick e2 which is why endoxifen is better but its just hard to source

 

[coolman985]

Why do you recommend non steroidal?

Any non-steroidal i.e., anastrazole or letrozole.

 

[aids]

Why do you recommend non steroidal?

Steroidal AI exhibits androgenic activity which can contribute to closure + is progressive so harder to dose safely.

 

[coolman985]

Steroidal AI exhibits androgenic activity which can contribute to closure + is progressive so harder to dose safely.

I agree about progressive part but how does the androgenic activity promote closure @Zagro

 

[7evenvox22]

I agree about progressive part but how does the androgenic activity promote closure @Zagro

it boosts igf-1 and local growth factors in the growth plate, which speeds up hypertrophy and ossification.

basically the same reason androgens fuse plates faster during puberty they amplify signaling that pushes chondrocytes toward maturation instead of proliferation.

 

[coolman985]

it boosts igf-1 and local growth factors in the growth plate, which speeds up hypertrophy and ossification.

basically the same reason androgens fuse plates faster during puberty they amplify signaling that pushes chondrocytes toward maturation instead of proliferation.

hmm i see but how would igf-1 cause maturation?

 

[7evenvox22]

hmm i see but how would igf-1 cause maturation?

It drives chondrocyte hypertrophy through mtor and erk pathways, so instead of keeping them in the proliferative zone, it pushes them to enlarge and calcify.

it’s good for growth short term but once hypertrophy dominates, the plate moves closer to fusion.

 

[coolman985]

It drives chondrocyte hypertrophy through mtor and erk pathways, so instead of keeping them in the proliferative zone, it pushes them to enlarge and calcify.

it’s good for growth short term but once hypertrophy dominates, the plate moves closer to fusion.

So do you recommend not using hgh?

 

[coolman985]

It drives chondrocyte hypertrophy through mtor and erk pathways, so instead of keeping them in the proliferative zone, it pushes them to enlarge and calcify.

it’s good for growth short term but once hypertrophy dominates, the plate moves closer to fusion.

also what doses of endoxifen do u recomend

 

[7evenvox22]

also what doses of endoxifen do u recomend

endoxifen hasn’t been used on humans yet, at least not for what we’re trying to target. there’s no data or trials on that application.
like @aids said, non-steroidal ai’s are the only real option for now until proper studies come out.
but, once there’s evidence and human data, i honestly think endoxifen would outperform non-steroidal ai’s for height-related use.
even tho most of this is cope and probably won’t work anyway.

 

[7evenvox22]

So do you recommend not using hgh?

of course not, it’s a solid compound. there’s a reason it’s in pretty much everyone’s stack.
i haven’t been on it that long myself but noticed some decent subtle improvements.
ask @Zagro , he’s probably been on it longer and has more experience with it.
edit: @coolman985 check pms, i sent you the sources.

 

[Spieldren]

Steroidal AI exhibits androgenic activity which can contribute to closure

This implies that androgen usage is bad for height increase but @Zagro pinned tren when actively trying to increase height?

 

[7evenvox22]

This implies that androgen usage is bad for height increase but @Zagro pinned tren when actively trying to increase height?

you clearly are a fucking retard and not as informed on this topic as we are.
the main thing behind plate closure is estrogen through the epiphyseal plate, it’s basically the only factor that fully closes them.
@Zagro used tren because it helps with igf-1 sensitivity while not converting to e2, which is exactly why it made sense in his case.
not saying it’s risk-free, but if you actually read into it, the logic tracks.
DYOR before posting stuff like this.
edit: you’re slightly right that androgenic activity can contribute to closure,
but epiphyseal plate signaling via estrogen is the main driver.
androgenic activity’s effect is much smaller and usually works indirectly through estrogen-related mechanisms.

 

[theübermenschboy]

Thread Song:

Spoiler: Song

Introduction:

Estrogen plays a paradoxical role in development. It’s one of the most important hormones for proper skeletal, neurological, and metabolic maturation, yet it’s also the single biggest factor responsible for growth plate closure. Globally suppressing estrogen through aromatase inhibitors can indeed prolong growth, but it comes at the cost of decreased bone quality, impaired brain development, and systemic dysfunction.

View attachment 4326889



So, the real question is:
Can you selectively inhibit estrogen locally in the growth plates without touching it elsewhere?
View attachment 4326765

Spoiler: Answer

Surprisingly, yes, there are multiple ways to modulate estrogenic activity at the tissue level without globally crashing E2.

The Case of Tamoxifen (Tamex):

Tamoxifen has long been studied as a selective estrogen receptor modulator (SERM), a compound that can act as an antagonist in some tissues and an agonist in others. However, its effects on bone and the growth plate are far more nuanced than people realize.

In the growth plate, Tamoxifen exhibits antagonistic properties, meaning it inhibits estrogen-mediated closure. Yet, paradoxically, it preserves or even promotes bone health in other tissues. This makes it a theoretically perfect candidate for localized modulation, at least on paper.

View attachment 4326781

The issue?
Tamoxifen also lowers IGF-1 levels significantly and exhibits ambiguous estrogenic activity in other tissues, including the liver and brain. This systemic interference makes it suboptimal for precise growth modulation.

View attachment 4326787

The Real Key: Tamoxifen’s Metabolites

Most people overlook the fact that Tamoxifen itself isn’t the true active compound responsible for these effects. Its metabolites are.

Among them, Endoxifen stands out. It binds to the estrogen receptor with over 100x the affinity of Tamoxifen itself, and its activity profile is much more selective. Another metabolite, Norendoxifen, has aromatase-inhibiting properties, but it’s Endoxifen that holds the most promise for targeted growth plate modulation.

View attachment 4326795

ERα Modulation: The Core Mechanism

The estrogen receptor alpha (ERα) has two major activation domains:

- AF-1: Promotes bone formation and maintains bone health.
- AF-2: Drives growth plate maturation and closure.

For controlled linear growth, the goal is simple, inhibit AF-2 while keeping AF-1 active.

Endoxifen accomplishes exactly that. It selectively antagonizes AF-2 while leaving AF-1 intact. Even more impressively, it promotes ERα degradation and blocks non-genomic signaling cascades like PKC/SET, which further drive hypertrophy and closure.

This dual action means you’re effectively shutting down the molecular switch that closes the plate, while preserving the receptor functions responsible for bone quality and skeletal strength.

View attachment 4326857

Why Endoxifen > Tamoxifen

- Higher ER Affinity: 100x stronger binding than Tamoxifen.
- Selective AF2 Antagonism: Inhibits closure while maintaining AF1-mediated bone integrity.
- Minimal IGF-1 Suppression: Much weaker hepatic ER signaling.
- Limited Central Activity: Reduced impact on neuroendocrine feedback.

Together, these make Endoxifen far more promising for local modulation of growth plates without the widespread drawbacks of full systemic estrogen blockade.

View attachment 4326865

Metabolic Considerations: CYP26D & Enzymatic Variability

The enzyme CYP26D is primarily responsible for Endoxifen metabolism. Anything that inhibits this enzyme will drastically alter the ratio of Tamoxifen metabolites, which can completely shift how the drug behaves in the body.
This is critical because several commonly used compounds can inhibit CYP26D, unintentionally changing Endoxifen’s balance and potency. Furthermore, species differences (rat vs human) explain why preclinical results often conflict with human data. These enzymes function differently across species, leading to vastly different outcomes in growth plate modulation.



Summary:

- Estrogen drives growth plate closure primarily via ERα AF2 activation.
- Tamoxifen antagonizes this pathway, but its systemic ambiguity limits usefulness.
- Endoxifen, its dominant metabolite, selectively blocks AF2 while leaving AF1 active, maintaining bone integrity while delaying closure.
- CYP26D determines metabolite balance inhibition alters effects.
- Localized estrogen modulation is theoretically possible, and Endoxifen appears to be one of the most promising routes toward achieving it.



If you enjoyed this thread, bookmark it. I’ll be releasing a follow-up soon, diving deeper into how to exploit tissue-selective receptor modulators to fine-tune estrogenic signaling for skeletal development.

View attachment 4326893



I apologize for my horrendous formatting. I seriously need someone to help me with it for my future threads.​

I am going to try this stuff . Nice thread btw

 

[Spieldren]

you clearly are a fucking retard and not as informed on this topic as we are.
the main thing behind plate closure is estrogen through the epiphyseal plate, it’s basically the only factor that fully closes them.
@Zagro used tren because it helps with igf-1 sensitivity while not converting to e2, which is exactly why it made sense in his case.
not saying it’s risk-free, but if you actually read into it, the logic tracks.
DYOR before posting stuff like this.

Okay pipe your ass down I quoted where aids said that androgenic activity contributes to closure and since tren is extremely androgenic compound I asked what's up with that.

Faggot coming at me like I said trenbolone closes growth plates