Bryan: Estrogen- Friend or Foe?

[Bryan]

Here's the abstract for the study I referred to previously. It may demonstrate a SECOND mechanism (other than the main one of how estrogen alters the release of gonadotropins) of how estrogen suppresses DHT. Take note, "purecontrol"! :wink:

One thing they don't mention in the abstract is that while 100 nM of 17b-estradiol was able to inhibit the synthesis of DHT in hair follicle dermal papillae by 60%, a much lower level of only 1 nM was also able to inhibit it by about the same amount.

Eur J Dermatol. 2001 May-Jun;11(3):195-8.
"Influence of estrogens on the androgen metabolism in different subunits of human hair follicles." Niiyama S, Happle R, Hoffmann R.
Department of Dermatology, Philipp University, Deutschhausstrasse 9, D-35033 Marburg, Germany.

The molecular pathways involved in estrogen-mediated induction of hair growth in androgenetic alopecia are unknown. Some authors found that estradiol (E) inhibited 5alpha-reductase (5alpha-R) activity and therefore we addressed the question whether 17alpha- or 17beta-E are able to modulate the activity of 5alpha-R, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) or 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in isolated compartments of human hair follicles. For this purpose, scalp biopsies from volunteers were taken and from each biopsy root sheaths, connective tissue sheaths and dermal papillae (DP) were dissected and incubated in the presence of 3H-testosterone (T) and, in addition, either 17alpha-E, 17beta-E, progesterone or finasteride for up to 48 hrs. Thereafter high-performance liquid chromatography analysis of culture supernatants was performed to detect T-metabolites. At the tested concentrations, finasteride was found to be a major inhibitor of dihydrotestosterone (DHT) formation. Even 1 nM finasteride inhibited DHT synthesis in DP by 86% and 1 nM progesterone by 75%. Estrogens were less able to inhibit the synthesis of DHT in DP (e.g. 100 nM 17alpha-E: 20%; 100 nM 17beta-E: 60%). Whether E directly inhibits 5alpha-R in DP's or whether the effect of estrogens might be explained by an increased conversion of T to the weaker androgens such as androstendione (via 17beta-HSD), androstenediol (via 3beta-HSD) or 17beta-E (via aromatase), thereby diminishing the amount of T available for the conversion to DHT, remains to be shown.

 

[purecontrol]

http://cancerres.aacrjournals.org/cgi/c ... 63/23/8516

Suppression of Estrogen Biosynthesis by Procyanidin Dimers in Red Wine and Grape Seeds
Elizabeth T. Eng12, JingJing Ye2, Dudley Williams2, Sheryl Phung2, Roger E. Moore2, Mary K. Young2, Ugis Gruntmanis3, Glenn Braunstein3 and Shiuan Chen12

1 City of Hope Graduate School of Biological Science and
2 Department of Surgical Research, Beckman Research Institute of the City of Hope, Duarte, California, and
3 Department of Medicine, Cedars-Sinai Medical Center-University of California at Los Angeles School of Medicine, Los Angeles, California

In breast cancer, in situ estrogen production has been demonstrated to play a major role in promoting tumor growth. Aromatase is the enzyme responsible for the conversion of androgen substrates into estrogens. This enzyme is highly expressed in breast cancer tissue compared with normal breast tissue. A wine extract fraction was recently isolated from red wine that exhibited a potent inhibitory action on aromatase activity. Using UV absorbance analysis, high-performance liquid chromatography profiling, accurate mass-mass spectrometry, and nanospray tandem mass spectrometry, most of the compounds in our red wine fraction were identified as procyanidin B dimers that were shown to be aromatase inhibitors. These chemicals have been found in high levels in grape seeds. Inhibition kinetic analysis on the most potent procyanidin B dimer has revealed that it competes with the binding of the androgen substrate with a Ki value of 6 µM. Because mutations at Asp-309, Ser-378, and His-480 of aromatase significantly affected the binding of the procyanidin B dimer, these active site residues are thought to be important residues that interact with this phytochemical. The in vivo efficacy of procyanidin B dimers was evaluated in an aromatase-transfected MCF-7 breast cancer xenograft model. The procyanidin B dimers were able to reduce androgen-dependent tumor growth, indicating that these chemicals suppress in situ estrogen formation. These in vitro and in vivo studies demonstrated that procyanidin B dimers in red wine and grape seeds could be used as chemopreventive agents against breast cancer by suppressing in situ estrogen biosynthesis.


A few things that have been drawn to my attention here is that bad estrogens cause cancer in men and women. These estrogens cause increased levels of tgf-betta not to mention other hormones responsible for containing the mess that bad estrogens make. This why we see the studies for Procyanidin B3 C1 and B1 for hair regrowth ie grape seed, apple, Chocamine, ect


Procyanidin's are what have the "SOD" like effect, the kicker here is that we know SOD helps regrow hair as it is the main ROS of the mitochondria, and the kicker? SOD acts as an antiestrogen.

 

[purecontrol]

All of the newly discovered polyphenols act to reduce estrogen effects, yet still acting as a weak estrogen. You can site that one specfic form of estradiol, but the consensus is that estradiol in general is not good for the body. It is not as simple as "estrogen is good" There are different estrogens and some are good, bad, and ugly.


16-hydroxy estrone and 4-hydroxy estrone, are linked to tumor growth and allow oxidation of cells, damage of DNA, and the promotion of cancer. And thus promotion of TGF-beta, and all the other inlamation and indicators that are always at the scene of hair loss.

two good estrogens, 2-hydroxy estradiol and 2-hydroxy estrone, now these estrogens act as anti-oxidants an thus as you have pointed out can actually help twoards growing hair back. When these two estrogens are low, tumor growth is more likely to occur and all the factors that cause hair loss.

Now the point here is that estrogen can cause hair loss or it can help grow hair as you have pointed out. However you are just simply leaving it up to the body, so some may have anything from excellent to absolute worst estrogen metabolism ie you may produce more good estrogen or more bad estrogen and as you age and as your estrogen levels stay high you are more and more likely to produce the bad estrogens that will cause many bad side effects including hair loss.

This could really explain why finasteride stops working even when DHT levels stay supressed. And why some people respond with more hair loss, also note that dutasteride increases estrogen levels even higher than finasteride.

Those that have good estrogen metabolism benefit the most and those with bad estrogen metabolism benefit the least or even increase hair loss.

So the goal is to produce more good estrogens and to keep estrogen at a normal level as even good estrogen at too high of a level will cause hair loss.

So far the only answer for this problem tha I have found would be DIM and/or I3C, SERMS are showing some promise as pointed out in the studies that I have posted, further more polyphenols that act as weak estrogens and powerful anti-oxidants will help to out compete the bad estrogens not to mention counter DHT and Testosterones effects.

 

[Bryan]

So the goal is to produce more good estrogens and to keep estrogen at a normal level as even good estrogen at too high of a level will cause hair loss.

Really? Then how do you explain the Kiesewetter et al studies and the Ohnemus et al study in which even clearly supraphysiological levels of 17b-estradiol accelerated the growth of human scalp hair follicle cells?

 

[purecontrol]

So the goal is to produce more good estrogens and to keep estrogen at a normal level as even good estrogen at too high of a level will cause hair loss.

Really? Then how do you explain the Kiesewetter et al studies and the Ohnemus et al study in which even clearly supraphysiological levels of 17b-estradiol accelerated the growth of human scalp hair follicle cells?

Yeah and I guess getting fat, growing breast, ect is fine also? The thing is that a normal level of estrogen can be high normal to low normal. It will be different for each person as to what is confortable for them, heck some people take sprio orally and don't care about the side effects but have regrown hair ect. Further more that will play a large part in genetics as to what one can handle, ie there is no one size fits all here.

So it is not a case of "estrogen is good, THE END" There needs to be more attention and detail there as certain estrogens do indeed have a dark side.

Further more you are talking about a very very specific estrogen, Bryan can you guarantee that I will only produce 17b-estradiol? Can you gurantee that for everyone in this forum or the world for that matter?

This is a good reason for people to pay more attention and get a simple blood or siliva test done to measure these levels. The point is that too much of anything will have unwanted side effects.

I'm not here to rain on your parade, I am simple here to make sense of the other side of the story, the studies show 100% that estrogen is not some golden ticket and that there is far far more to it than than some gerneralized rubber stamp.

Even you yourself were suprised of the findings of those studies, you know that there is something more to this.

IMO this really explains why when you are young you end up with so much hair, it is an extremely healthy metabolism of hormones and a proper cascade of those hormones, as you age and become less healthy you end up with improper cascade and more hormones ie anearobic ones, end up being much higher than they should getting higher and higher and staying at a more and more extended time. So you loss more and more hair and grow less and less back, in general.

IMO this really explains why the people that don't respond to finasteride end up with such bad side effects, these side effects showing estrogen dominance. While others on the other side see nothing but good, perhaps they have a better estrogen metabolism making more good estrogen while the others make more bad estrogen making the problem even worse.

 

[docj077]

So the goal is to produce more good estrogens and to keep estrogen at a normal level as even good estrogen at too high of a level will cause hair loss.

Really? Then how do you explain the Kiesewetter et al studies and the Ohnemus et al study in which even clearly supraphysiological levels of 17b-estradiol accelerated the growth of human scalp hair follicle cells?

Yeah and I guess getting fat, growing breast, ect is fine also? The thing is that a normal level of estrogen can be high normal to low normal. It will be different for each person as to what is confortable for them, heck some people take sprio orally and don't care about the side effects but have regrown hair ect. Further more that will play a large part in genetics as to what one can handle, ie there is no one size fits all here.

So it is not a case of "estrogen is good, THE END" There needs to be more attention and detail there as certain estrogens do indeed have a dark side.

Further more you are talking about a very very specific estrogen, Bryan can you guarantee that I will only produce 17b-estradiol? Can you gurantee that for everyone in this forum or the world for that matter?

This is a good reason for people to pay more attention and get a simple blood or siliva test done to measure these levels. The point is that too much of anything will have unwanted side effects.

I'm not here to rain on your parade, I am simple here to make sense of the other side of the story, the studies show 100% that estrogen is not some golden ticket and that there is far far more to it than than some gerneralized rubber stamp.

Even you yourself were suprised of the findings of those studies, you know that there is something more to this.

IMO this really explains why when you are young you end up with so much hair, it is an extremely healthy metabolism of hormones and a proper cascade of those hormones, as you age and become less healthy you end up with improper cascade and more hormones ie anearobic ones, end up being much higher than they should getting higher and higher and staying at a more and more extended time. So you loss more and more hair and grow less and less back, in general.

IMO this really explains why the people that don't respond to finasteride end up with such bad side effects, these side effects showing estrogen dominance. While others on the other side see nothing but good, perhaps they have a better estrogen metabolism making more good estrogen while the others make more bad estrogen making the problem even worse.

First of all, estrogen doesn't make you "fat." In fact, it does quite the opposite. Estrogen is required for the regulation of fat deposition in adipose tissue. In experimental models, animals that are engineered to lack functional aromatase, and thus, estrogen, are commonly obese.

Second, looking at this in terms of estrogen metabolites is probably the wrong way of going about this. Estrogen metabolites are nice and reading some random website about estrogen dominance simply makes your opinion incomplete. The activities of the various types of estrogen aren't regulated by the molecules themselves, but by the particular estrogen receptor that they bind to. Estrogen metabolites binding to one receptor type will cause one type of cellular response while their binding to another receptor type will likely cause the complete opposite response. The different responses to finasteride with regards to estrogens is probably due more to estrogen receptor deposition and concentration at the cellular level of any given individual rather than differing cellular outcomes by any given estrogen metabolite. The tissue being affected and the metabolic state of that tissue must be taken into account.

Lastly, I don't understand what you mean by "aerobic vs. anaerobic metabolism of estrogen." All estrogen metabolism takes place primarily in the liver. It's a process that begins with hydroxylation in phase I, methylation, glucoronidation, or sulfation in phase II, and finally, excretion in the urine and feces. I do not recall a specific oxidative or reductive step that can be altered. If you're aware of that O2 requiring step, then please enlighten us all. The active estrogens are commonly converted between each other and nobody produces just 17beta-estradiol.

 

[purecontrol]

nobody produces just 17beta-estradiol.

Exactly but I am willing to bet that certain people will produce a lot more than others. And that others will produce more estrogen that will negatively effect hair directly or not. Same goes for DHT, but I don't see them leaving it up to nature to just give them less DHT


Im not quite sure what the problem is? ie testosterone does not necessarily have to convert to DHT same goes for estrogens and that is exactly what the easy to read website sites. I really don't see a problem with siting the website itself instead fo reposting every single study as there are hundreds.

I'm not sure about you but I think I will skip on the cancer causing estrogen metabolites, as that induces TGF-Beta and ect.

As for it's actual aplication that is to be seen, for me nothing means anything until you actually see some real world reasults which are completely different from a lab ie in vitro vivo ect in some petri dish.

The point here is that not all estrogen is created equally, but obviously some estrogen when in an abnormal amount and/or duration caused unwanted side effects while others have wanted effects.

The goal is to increase the ones that we want and decrease the ones we don't, now that is easier said than done as we are not entirely sure what are the ones we want for hair regrowth.

But IMO like I said I will skip the ones that cause cancer and go for the ones that don't.

 

[Bryan]

So the goal is to produce more good estrogens and to keep estrogen at a normal level as even good estrogen at too high of a level will cause hair loss.

Really? Then how do you explain the Kiesewetter et al studies and the Ohnemus et al study in which even clearly supraphysiological levels of 17b-estradiol accelerated the growth of human scalp hair follicle cells?

Yeah and I guess getting fat, growing breast, ect is fine also?...So it is not a case of "estrogen is good, THE END" There needs to be more attention and detail there as certain estrogens do indeed have a dark side. (snip rest of anti-estrogen spiel)

What the hell are you talking about?? I didn't say anything about whether estrogen is uniformly good for the human body, I asked you a SPECIFIC QUESTION about the effect of estrogen on human scalp hair growth, which you never answered.

Do you know what a "straw-man" argument is? That's a fallacy in rhetoric when you address NOT the question you were asked, but you set-up some DIFFERENT question which you were NOT asked, then procede to tear it down, making everybody think that the original question was answered. Sorry, but I'm not letting you get away with that.

Once again, you made the following claim: "...even good estrogen at too high of a level will cause hair loss."

Here is my response to that claim: Really? Then how do you explain the Kiesewetter et al studies and the Ohnemus et al study in which even clearly supraphysiological levels of 17b-estradiol accelerated the growth of human scalp hair follicle cells?

This time, please answer the question that I asked you, and don't go off on some other unrelated tangent.

 

[docj077]

nobody produces just 17beta-estradiol.

Exactly but I am willing to bet that certain people will produce a lot more than others. And that others will produce more estrogen that will negatively effect hair directly or not. Same goes for DHT, but I don't see them leaving it up to nature to just give them less DHT


Im not quite sure what the problem is? ie testosterone does not necessarily have to convert to DHT same goes for estrogens and that is exactly what the easy to read website sites. I really don't see a problem with siting the website itself instead fo reposting every single study as there are hundreds.

I'm not sure about you but I think I will skip on the cancer causing estrogen metabolites, as that induces TGF-Beta and ect.

As for it's actual aplication that is to be seen, for me nothing means anything until you actually see some real world reasults which are completely different from a lab ie in vitro vivo ect in some petri dish.

The point here is that not all estrogen is created equally, but obviously some estrogen when in an abnormal amount and/or duration caused unwanted side effects while others have wanted effects.

The goal is to increase the ones that we want and decrease the ones we don't, now that is easier said than done as we are not entirely sure what are the ones we want for hair regrowth.

But IMO like I said I will skip the ones that cause cancer and go for the ones that don't.

So, why are you so concerned with the metabolites of estrogen? You're right about certain metabolites being protective and others causing cellular damage, but the problem is with individual estrogen metabolism in the liver. That particular system can be manipulated with soy products and lignans. 17beta-estradiol is quite protective and in fact has been shown in studies to pretty much completely or partially attenuate the concentrations of TGF-beta and many other molecular pathways involved in male pattern baldness including the SMAD signaling pathway, the TGF-beta receptor system, and collagen expression and deposition. In fact, in certain animal models, E2 has been shown to partially reverse diabetic renal disease.

 

[Bryan]

Exactly but I am willing to bet that certain people will produce a lot more than others. And that others will produce more estrogen that will negatively effect hair directly or not.

Please provide a reference or citation for the claim that estrogen negatively affects hair. (HINT: stick to what I'm requesting, and don't go off on some other tangent! )

The point here is that not all estrogen is created equally, but obviously some estrogen when in an abnormal amount and/or duration caused unwanted side effects while others have wanted effects.

Reference or citation, please. (Stick to what I'm specifically requesting!)

 

[purecontrol]

nobody produces just 17beta-estradiol.

Exactly but I am willing to bet that certain people will produce a lot more than others. And that others will produce more estrogen that will negatively effect hair directly or not. Same goes for DHT, but I don't see them leaving it up to nature to just give them less DHT


Im not quite sure what the problem is? ie testosterone does not necessarily have to convert to DHT same goes for estrogens and that is exactly what the easy to read website sites. I really don't see a problem with siting the website itself instead fo reposting every single study as there are hundreds.

I'm not sure about you but I think I will skip on the cancer causing estrogen metabolites, as that induces TGF-Beta and ect.

As for it's actual aplication that is to be seen, for me nothing means anything until you actually see some real world reasults which are completely different from a lab ie in vitro vivo ect in some petri dish.

The point here is that not all estrogen is created equally, but obviously some estrogen when in an abnormal amount and/or duration caused unwanted side effects while others have wanted effects.

The goal is to increase the ones that we want and decrease the ones we don't, now that is easier said than done as we are not entirely sure what are the ones we want for hair regrowth.

But IMO like I said I will skip the ones that cause cancer and go for the ones that don't.

So, why are you so concerned with the metabolites of estrogen? You're right about certain metabolites being protective and others causing cellular damage, but the problem is with individual estrogen metabolism in the liver. That particular system can be manipulated with soy products and lignans. 17beta-estradiol is quite protective and in fact has been shown in studies to pretty much completely or partially attenuate the concentrations of TGF-beta and many other molecular pathways involved in male pattern baldness including the SMAD signaling pathway, the TGF-beta receptor system, and collagen expression and deposition. In fact, in certain animal models, E2 has been shown to partially reverse diabetic renal disease.

Exactly, so do what you can to keep as much good estrogen as possibile. But the point is that even if you have just 100% of 17beta-estradiol if the level is too high and you are getting fat, growing breasts, other side effects then you need to lower the levels.

That is really going to depend on each person, further more we are not sure what estrogen/s are causing the hyper AR activity.

The studies show that even with the still high DHT levels that the SERM was putting an end to the BHP.



The point is that there is more to it, needs more research, and it is the other side of hair loss.

 

[Bryan]

That is really going to depend on each person, further more we are not sure what estrogen/s are causing the hyper AR activity.

What do you mean by "hyper AR activity"?

The studies show that even with the still high DHT levels that the SERM was putting an end to the BHP.

I've already cited for you the study in which an aromatase inhibitor had no effect on BPH.

 

[docj077]

That is really going to depend on each person, further more we are not sure what estrogen/s are causing the hyper AR activity.

What do you mean by "hyper AR activity"?

The studies show that even with the still high DHT levels that the SERM was putting an end to the BHP.

I've already cited for you the study in which an aromatase inhibitor had no effect on BPH.

A SERM and an aromatase inhibitor are two different classes of drugs. You'd think that the response would be the same to both drugs, however.

 

[Bryan]

A SERM and an aromatase inhibitor are two different classes of drugs.

Yes, I know.

You'd think that the response would be the same to both drugs, however.

Yes. One would expect both of them to have similar effects.

I've read some of Wells E. Farnsworth's articles on prostate disease, and it's fascinating how doctors are getting more and more suspicious about the role of estrogen in prostate cancer and BPH. And yet STILL, there was no effect on BPH from the aromatase inhibitor used in that study I've cited several times for "purecontrol". Worse still, many of these anti-estrogen fanatics continue to blame estrogen even for BALDING, based on some very specious guilt-by-association reasoning!

 

[docj077]

A SERM and an aromatase inhibitor are two different classes of drugs.

Yes, I know.

You'd think that the response would be the same to both drugs, however.

Yes. One would expect both of them to have similar effects.

I've read some of Wells E. Farnsworth's articles on prostate disease, and it's fascinating how doctors are getting more and more suspicious about the role of estrogen in prostate cancer and BPH. And yet STILL, there was no effect on BPH from the aromatase inhibitor used in that study I've cited several times for "purecontrol". Worse still, many of these anti-estrogen fanatics continue to blame estrogen even for BALDING, based on some very specious guilt-by-association reasoning!

If you want to get really crazy about prostate cancer, it's entirely possible. Hormones, diet, genetics, and even viruses have all been linked at one time or another. It's likely a combination of all of them with the key predisposing factor being genetics. Afterall, it's clearly a disease that runs in families. I'd have to say that age is very important, as well. The human body breaks down as it gets older. It's not surprising that the cell populations begin to do the same over time, too, and there is nothing that we can medically or personally do about it.

I knew that you knew the difference between the drug classes. I just wanted to make sure that other people viewing the forum knew that they were different classes of drugs for their own research purposes.

 

[jimmystanley]

bryan... since your concerned mainly for the newbies being misinformed by someone with "new" ideas it would probably look better on your part to refrain from name calling and being so quick to bash out his ideas.
I was also wondering why you haven't talked about using an anti aromatase in combination with a DHT inhibitor like finasteride? You admit that estrogen causes a decrease in free testosterone which you deem as good since in leaves less to become DHT and thus, estrogen protects the hair follicle (indirectly). But what about the benefits of testosterone? For sex, for muscle maintenance, anti depression... there are tonnes of benefits to it (and if you want some "scientific articles so that i don't look like i'm "making this stuff up as i go" i will find the time)
But what about learning about lowering estrogen levels and DHT levels? I think that purecontrol even pointed out that you do need certain levels of estrogen.

 

[abcdefg]

What causes body hair and facial hair growth at puberty exactly? So estrogen starts some hair growing in certain spots as Docj said, DHT supposedly triggers body hair to grow. I heard testosterone is needed to sustain body and facial hair growth once its triggered to start by dht. Has anyone tried reducing or removing all 3 of these before puberty to see if hair grows at all? Wouldnt answering that question really help a lot if male pattern baldness is really caused by the reverse action of these 3 things? so estrogen starts hair growth in the pubic areas and is beneficial to head hair growth, but testosterone and dht trigger body hair growth but damage head hair? why is this?

 

[Bryan]

bryan... since your concerned mainly for the newbies being misinformed by someone with "new" ideas it would probably look better on your part to refrain from name calling and being so quick to bash out his ideas.

Are you talking about my responses to the poster "purecontrol"? Without going back and re-reading them again, I don't even recall any name-calling on my part; but if you say I did do that, I'll take your word for it.

If I'm quick to bash his ideas, it's because I have REPEATEDLY cited the evidence to refute his claims, but he doesn't listen to what I say. As the old saying goes, sometimes you have to crack a mule over the head with a two-by-four, just to get his attention! :mrgreen:

I was also wondering why you haven't talked about using an anti aromatase in combination with a DHT inhibitor like finasteride? You admit that estrogen causes a decrease in free testosterone which you deem as good since in leaves less to become DHT and thus, estrogen protects the hair follicle (indirectly).

That's not the ONLY way that estrogen helps scalp hair follicles, because it also stimulates their growth even when given to in vitro cultures. It probably has beneficial genetic effects via the estrogen receptor.

But what about the benefits of testosterone? For sex, for muscle maintenance, anti depression... there are tonnes of benefits to it

Of course! I'm very interested in possibly fighting some of the degenerative aging effects in men with the prudent use of aromatase inhibitors. However, I have grave suspicions that it may be a long time (if ever) that doctors and researchers ever really get around to testing that theory in a serious fashion.

 

[Jake_89]

Hang on a minute what about AI's like Aromasin they don't reduce Estrogen in the blood nor do they stop production of Estrogen they simply prevent it from binding at receptors so having high estrogen due to finasteride floating in your blood but not being able to bind wont that trick the brain into not producing MORE Test?

 

[Bryan]

...so having high estrogen due to finasteride floating in your blood but not being able to bind wont that trick the brain into not producing MORE Test?

How would it do THAT? It seems to me that taking an estrogen receptor blocker would make the available estrogen "invisible", so-to-speak, increasing the production of testosterone.