What is estrogen's role in converting HGH to igf-1?

[BigTomJ]

Purely detrimental (in humans) since estrogens increase IGFBP-1. However, aromatization (the process of converting T to E2) increases it. So there’s a parabolic shape to the E2/curve in men (for whom all E2 is the product of T aromatization) where that plateauing is caused by E2/IGFBP-1.

so, in layman's terms, then for any given individual there should be some sort of "sweet spot" where aromatization promotes increased IGF1 conversion, but total estrogens are not elevated enough to significantly increase IGFBPs.

that is if I'm understanding you correctly.

It seems to be that the developing consensus among some of the more science forward voices in the community, namely Kurt Havens and Todd Lee recently, that estrogen towards the upper end of the reference range or slightly outside of the RR seems to be that sweet spot for most people.

Would you say your research and knowledge on the mechanisms would fall in line with that consensus?

 

[Type-IIx]

so, in layman's terms, then for any given individual there should be some sort of "sweet spot" where aromatization promotes increased IGF1 conversion, but total estrogens are not elevated enough to significantly increase IGFBPs.

that is if I'm understanding you correctly.

It seems to be that the developing consensus among some of the more science forward voices in the community, namely Kurt Havens and Todd Lee recently, that estrogen towards the upper end of the reference range or slightly outside of the RR seems to be that sweet spot for most people.

Would you say your research and knowledge on the mechanisms would fall in line with that consensus?

The “Goldilock’s Zone” relates to AI use, basically you want to dial in your AI dose for each blast/cycle.

I don’t want to give you what my observation has been about ideal E2. But I do have one. It’s just not something I want to put out there because it’s something I apply for my guys and any arbitrary value I give will just lead to controversy/disagreement inevitably.

 

[BigTomJ]

The “Goldilock’s Zone” relates to AI use, basically you want to dial in your AI dose for each blast/cycle.

of course, i was just checking if its was mechanistically sound to you

I don’t want to give you what my observation has been about ideal E2. But I do have one. It’s just not something I want to put out there because it’s something I apply for my guys and any arbitrary value I give will just lead to controversy/disagreement inevitably.

oh of course, its all going to be so individual i wasnt looking for a "between x and y is ideal" type blanket statement. such a statement would just get parroted around without understanding the nuance behind it.

 

[Type-IIx]

of course, i was just checking if its was mechanistically sound to you


oh of course, its all going to be so individual i wasnt looking for a "between x and y is ideal" type blanket statement. such a statement would just get parroted around without understanding the nuance behind it.

It is mechanistically sound but there’ll be disagreement about the arbitrary values. Indeed, the individuality factor is substantial. I can however speak to what seems to be too low for MOST guys, which is < 20 pg/mL. Depending on objective, i.e., bulking, you might want to let it go out of range high.

But the reason you do so is not because E2 benefits IGF-I. Rather, it’s because inhibiting aromatase downregulates IGF-I expression.

 

[Type-IIx]

It is mechanistically sound but there’ll be disagreement about the arbitrary values. Indeed, the individuality factor is substantial. I can however speak to what seems to be too low for MOST guys, which is < 25 pg/dL. Depending on objective, i.e., bulking, you might want to let it go out of range high.

But the reason you do so is not because E2 benefits IGF-I. Rather, it’s because inhibiting aromatase downregulates IGF-I expression.

Excuse me, < 20 pg/mL.

 

[BigTomJ]

It is mechanistically sound but there’ll be disagreement about the arbitrary values. Indeed, the individuality factor is substantial.

Fully agree

I can however speak to what seems to be too low for MOST guys, which is < 25 pg/dL. Depending on objective, i.e., bulking, you might want to let it go out of range high.

That sounds about right to me as well and from what ive seen with my own bloodwork and experiences

But the reason you do so is not because E2 benefits IGF-I. Rather, it’s because inhibiting aromatase downregulates IGF-I expression.

Is it solely the lack of downregulation with no other interaction? Weve seen individuals showing a parabolic increase in serum IGF-1 scores seemingly in direct coloration to total estrogens, even without the use of an AI as an additional variable.

is it possible that, simply by allowing more systemic serum e2 allows for more saturation of the ER, and thus less serum IGF-1 being bound to the ER resulting in it appearing to be higher in bloodwork?


This article has some information about IGF-1/estrogen relationship mainly in the subject of breast cancer.

https://www.sciencedirect.com/science/article/pii/S0022316622150133#bib9

The emerging model of cross-talk between insulin-like growth factor-I (IGF-I)3 and estrogens suggests that estrogens, acting through the estrogen receptor (ER), induce the expression of IGF-I.

IGFs dramatically increase cell proliferation in the presence of estrogen (9). Based on these observations, it has been suggested that estradiol and IGF-I may act together to stimulate proliferation in normal mammary epithelium and increase the risk of breast cancer. In fact estrogens regulate the expression of IGF-I and IGF receptor I in ER-positive breast cancer cell lines as well as in neuroblastoma cells (10), in uterine tissue (11,12) and in osteoblasts (11).

Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells.

Estrogen sensitizes the MCF-7 estrogen-responsive breast cancer cell line to the mitogenic effect of insulin and the insulin-like growth factors (IGFs…

www.sciencedirect.com

Binding experiments with 125I-IGF-I and hybridization of a type I IGF receptor probe to RNA showed that the levels of the type I IGF receptor and its mRNA are increased 7- and 6.5-fold, respectively, by estradiol.

Im very far from an expert and this is still a subject im reading on, but it seems like there is more to the relationship between e2/ER/IGF-1/IGFR.

interested in your thoughts

 

[egruberman]

It seems to be that the developing consensus among some of the more science forward voices in the community, namely Kurt Havens and Todd Lee recently, that estrogen towards the upper end of the reference range or slightly outside of the RR seems to be that sweet spot for most people.

I'm not sure their opinions are in agreement. Todd Lee has suggested that running e2 higher than the reference range has benefits to IGF-1 conversion, which is based on his understanding of the mechanism of action. Seems like conjecture to me. Kurt Havens explicitly recommends keep e2 in the top of the reference range and has said to me that there's no research to support Dr. Lee's conjecture.

I'm still trying to arrive at an understanding on the topic, but my interpretation of the statements by @Type-IIx is that running it too high is counterproductive.

 

[BigTomJ]

I'm not sure their opinions are in agreement. Todd Lee has suggested that running e2 higher than the reference range has benefits to IGF-1 conversion, which is based on his understanding of the mechanism of action. Seems like conjecture to me. Kurt Havens explicitly recommends keep e2 in the top of the reference range and has said to me that there's no research to support Dr. Lee's conjecture.

they definitely dont agree and i thin theyve said so explicitly.
I put greater stock into kurts opinion as todd seems to be more subject to sensationalism and emotionally attached to his conclusions. i only mentioned them both since they have both been talking about the subject recently across multiple shows and podcasts.

I'm still trying to arrive at an understanding on the topic, but my interpretation of the statements by @Type-IIx is that running it too high is counterproductive.

I think thats pretty clear.

as type-iix said, with elevated estrogens comes more IGFBP's, most notably IGFBP-1 which seems to be largely useless, while the 5 other IGFBP's may or may not be elevated with estrogens, but might serve some beneficial use.

and its well documented (coincidentally even in the article i cited above) the downregulation of IGF-1 in the presence of AI agents.

The whole subject of IGF/IGFBP and sex hormone interactions is actually quite fascinating

Frontiers | IGF-Binding Proteins: Why Do They Exist and Why Are There So Many?

Insulin-like growth factors (IGFs) are key growth-promoting peptides that act as both endocrine hormones and autocrine/paracrine growth factors. In the blood...

www.frontiersin.org

Testosterone and Estradiol Regulate Free IGF-I, IGFBP-1 and Dimeric IGF-I/IGFBP-1 Concentrations - PMC

The present study tests the clinical postulate that elevated testosterone (Te) and estradiol (E2) concentrations modulate the effects of constant iv infusion of saline vs recombinant human IGF-I on free IGF-I, IGFBP-1 and dimeric IGF-I/IGFBP-1 ...

www.ncbi.nlm.nih.gov

 

[29trt]

So if too much AI's have a detrimental effect regarding igf-1 would adding a serm to a cycle be better?
or maybe have a cycle that includes masteron instead of an AI?

 

[jdubzzz44]

they definitely dont agree and i thin theyve said so explicitly.
I put greater stock into kurts opinion as todd seems to be more subject to sensationalism and emotionally attached to his conclusions. i only mentioned them both since they have both been talking about the subject recently across multiple shows and podcasts.


I think thats pretty clear.

as type-iix said, with elevated estrogens comes more IGFBP's, most notably IGFBP-1 which seems to be largely useless, while the 5 other IGFBP's may or may not be elevated with estrogens, but might serve some beneficial use.
View attachment 288044
and its well documented (coincidentally even in the article i cited above) the downregulation of IGF-1 in the presence of AI agents.

The whole subject of IGF/IGFBP and sex hormone interactions is actually quite fascinating

Frontiers | IGF-Binding Proteins: Why Do They Exist and Why Are There So Many?

Insulin-like growth factors (IGFs) are key growth-promoting peptides that act as both endocrine hormones and autocrine/paracrine growth factors. In the blood...

www.frontiersin.org

Testosterone and Estradiol Regulate Free IGF-I, IGFBP-1 and Dimeric IGF-I/IGFBP-1 Concentrations - PMC

The present study tests the clinical postulate that elevated testosterone (Te) and estradiol (E2) concentrations modulate the effects of constant iv infusion of saline vs recombinant human IGF-I on free IGF-I, IGFBP-1 and dimeric IGF-I/IGFBP-1 ...

www.ncbi.nlm.nih.gov

Kurt has been pretty adamant on saying there is no reason to run estrogen high ever. I also believe he said the higher e2 the less igf1 which is opposite of todd lee saying run it super high like over double the reference range for more igf1.

 

[BigTomJ]

So if too much AI's have a detrimental effect regarding igf-1 would adding a serm to a cycle be better?
or maybe have a cycle that includes masteron instead of an AI?

Probably not just because there are wider reaching negatives from serms than AIs, imo.

Honestly, I think regarding all the information, standard practice still remains pretty close to best practice.
That practice being;
"Use an AI if your e2 is way out of range, but just don't crush your estrogen"

 

[Type-IIx]

Are Kurt and Todd the gurus or what? lol. Jesus it’s like a sewing circle in here. There’s not much controversy if you’re off YouTube

 

[Type-IIx]

So if too much AI's have a detrimental effect regarding igf-1 would adding a serm to a cycle be better?
or maybe have a cycle that includes masteron instead of an AI?

Yes although Masteron is an AI

 

[egruberman]

Are Kurt and Todd the gurus or what? lol. Jesus it’s like a sewing circle in here. There’s not much controversy if you’re off YouTube

Kurt is a PhD candidate in endocrinology and is focusing his work specifically on performance enhancing drugs. I have a great deal of respect for his opinions. Todd Lee is a medical doctor and an IFBB pro. I have less respect for his opinions, but he's entertaining nonetheless.

 

[Deleted member 59947]

Im very far from an expert and this is still a subject im reading on, but it seems like there is more to the relationship between e2/ER/IGF-1/IGFR.

interested in your thoughts

 

[Deleted member 59947]

Are Kurt and Todd the gurus or what? lol. Jesus it’s like a sewing circle in here. There’s not much controversy if you’re off YouTube

Hahahahahah exactly lol

 

[Deleted member 59947]

It seems to be that the developing consensus among some of the more science forward voices in the community, namely Kurt Havens and Todd Lee recently, that estrogen towards the upper end of the reference range or slightly outside of the RR seems to be that sweet spot for most people.

Nothing to do with science, it has to do with a trend that started with Keith Nichols and Neal Rouzier on youtube in 2019, two clowns giving the "let your e2 as high as you can" advice

 

[Deleted member 59947]

of course, i was just checking if its was mechanistically sound to you


oh of course, its all going to be so individual i wasnt looking for a "between x and y is ideal" type blanket statement. such a statement would just get parroted around without understanding the nuance behind it.

You seem so scared of typeII in the way you write, relax budy

 

[29trt]

Yes although Masteron is an AI

I based that on what Kurt Havens said about the metabolites of Masteron acting more like a serm than an AI.

I have seen bloodwork posted from people running Mast that shows lower E2, that would indicate aromatization inhibiting effects but other people seem to not get this effect so I thought it was possible that it might actually act as a serm as serms do not lower serum estrogen, correct?

 

[BigTomJ]

Nothing to do with science, it has to do with a trend that started with Keith Nichols and Neal Rouzier on youtube in 2019, two clowns giving the "let your e2 as high as you can" advice

Congratulations, you didn't understand the topic being discussed at all.
You aren't mentally capable of contributing to this conversation, it's beyond your capacity, so go sit back and run your sack with your greasy dermals.

You seem so scared of typeII in the way you write, relax budy

Shhhh, the adults are talking, go back to your coloring books.