Oral Steroid Made My Hair Grow Back Thicker!

[czecha]

Shouldnt dexamethasone be the cure (with sides) if your theory was correct chemhead?
it‘s not only a GS but also increases aromatase expression I have read

 

[ChemHead]

Shouldnt dexamethasone be the cure (with sides) if your theory was correct chemhead?
it‘s not only a GS but also increases aromatase expression I have read

Possibly, but the body is much more complex than just dumping a chemical in it. The question is whether dexamethasone is able to enter the area it needs to be (likely nuclear estrogen receptors in hair follicles). If it had access and is allowed through the membrane, it's possible that it may have a positive effect if the effect is strong enough within the cell without causing negative effects inside the body. The problem with most treatments in general is that they're not location selective or specific... They're systemic. And the problem with that is that, generally, whatever effects the drug causes outside the intended target tends to alter steroid metabolizing enzyme expression or steroid receptor expression throughout the entire body and then the net effect of the drug is essentially nullified in the target area. This is what happens with finasteride. This is even what happens with body builders that inject anabolic steroids... The body is constantly trying to counterbalance what you're doing to it because it's protecting itself. That's why the only real solution, when it is found, will likely involve some type of smart drug that is only active within the targeted area, or it will literally just be genetic engineering to alter expression of enzymes and steroid receptors (best, easiest, and more likely option).

 

[ChemHead]

I think originally if it was this thread or a similar one someone posted they used Anavar (Oxandrolone) for 7 weeks, which resulted in significant overall hair growth.
The thread has digressed into a discussion of obscure biological interactions of equally obscure cellular interactions which just obfuscates the original claim. The question to me is: Has anyone else experienced significant hair growth using Anavar (Oxandrolone)? I understand there is even a cream. Thanks!

I've explained why anavar works. I don't remember what thread it was in, but it was probably a couple years ago.

Anavar works in a way similar to finasteride. Where finasteride is a 5AR antagonist, Anavar actually has two mechanisms of action:

1. Anavar is a competitive 5AR agonist, meaning that it competes with other steroids for binding the 5AR enzyme. However, because it's an agonist (and unlike finasteride), it actually produces a 5a-reduced steroid and it doesn't stay bound to and permanently denature the 5AR enzyme.

2. Anavar and it's 5a-reduced metabolite are competitive androgen receptor agonists.

So, taking these two things into consideration:
Anavar is competing with testosterone for 5AR and "winning" because it has a higher affinity than testosterone. This increases the concentration of testosterone (since less is being 5a-reduced) and then, both Anavar and it's 5a-reduced metabolite are binding the androgen receptor with higher affinity than testosterone.

So, binding both the 5AR enzyme, as well as the androgen receptor, this is:

1. Leaving a higher concentration of testosterone to be aromatized

2. Maintaining aromatase and estrogen receptor expression, which is positively regulated by binding of the androgen receptor

What you ultimately end up with is a scenario where your body is using Anavar in place of testosterone for both binding of 5AR and the androgen receptor, while leaving testosterone behind so that it may be used for what is ultimately good for hair, which is aromatization and estrogen receptor activation. And it does this all while maintaining androgen receptor induced estrogenic receptor expression.

In my opinion, not only is Anavar far safer than finasteride, it should theoretically work better because of its ability to maintain nuclear estrogen receptor and aromatase expression. Hair growth and thickening isn't happening because estrogens are floating into the hair follicle and binding the estrogen receptor. It doesn't work that way. The estrogens are manufactured within the cell... they don't come from serum estrogen concentrations. Because of this, the health of your hair is dependent upon estrogen receptor expression, aromatase expression, and the concentration of substrate (testosterone and estradiol, resp.) available to binding those two proteins. If any of these are off, hair growth and quality are affected.

 

[czecha]

I've explained why anavar works. I don't remember what thread it was in, but it was probably a couple years ago.

Anavar works in a way similar to finasteride. Where finasteride is a 5AR antagonist, Anavar actually has two mechanisms of action:

1. Anavar is a competitive 5AR agonist, meaning that it competes with other steroids for binding the 5AR enzyme. However, because it's an agonist (and unlike finasteride), it actually produces a 5a-reduced steroid and it doesn't stay bound to and permanently denature the 5AR enzyme.

2. Anavar and it's 5a-reduced metabolite are competitive androgen receptor agonists.

So, taking these two things into consideration:
Anavar is competing with testosterone for 5AR and "winning" because it has a higher affinity than testosterone. This increases the concentration of testosterone (since less is being 5a-reduced) and then, both Anavar and it's 5a-reduced metabolite are binding the androgen receptor with higher affinity than testosterone.

So, binding both the 5AR enzyme, as well as the androgen receptor, this is:

1. Leaving a higher concentration of testosterone to be aromatized

2. Maintaining aromatase and estrogen receptor expression, which is positively regulated by binding of the androgen receptor

What you ultimately end up with is a scenario where your body is using Anavar in place of testosterone for both binding of 5AR and the androgen receptor, while leaving testosterone behind so that it may be used for what is ultimately good for hair, which is aromatization and estrogen receptor activation. And it does this all while maintaining androgen receptor induced estrogenic receptor expression.

In my opinion, not only is Anavar far safer than finasteride, it should theoretically work better because of its ability to maintain nuclear estrogen receptor and aromatase expression. Hair growth and thickening isn't happening because estrogens are floating into the hair follicle and binding the estrogen receptor. It doesn't work that way. The estrogens are manufactured within the cell... they don't come from serum estrogen concentrations. Because of this, the health of your hair is dependent upon estrogen receptor expression, aromatase expression, and the concentration of substrate (testosterone and estradiol, resp.) available to binding those two proteins. If any of these are off, hair growth and quality are affected.

The question is, where are the internet anecdotes backing this up?

I think Nandrolone, as you yourself pointed out in this thread, is more promising. Also because it was prevalent in 70s Bodybuilding, and 70s Bodybuilding had lots of nice hairlines.
Regardless, everything will suppress hpta

 

[ChemHead]

The question is, where are the internet anecdotes backing this up?

I think Nandrolone, as you yourself pointed out in this thread, is more promising. Also because it was prevalent in 70s Bodybuilding, and 70s Bodybuilding had lots of nice hairlines.
Regardless, everything will suppress h

The only anecdote I know of is the one that I originally found on this forum, but I haven't actually looked for any more anecdotes for a couple years, so there may be more.

I think the reason we don't see more anecdotes, though, is simply due to perspective. Most people don't see anavar/nandrolone through the lens that I do. They see an anabolic steroid. I see a steroidal competitive 5AR agonist that also happens to have a side benefit of being anabolic.

So, we don't see more anecdotes because most people don't even see anavar as something they should experiment with for hair loss.

 

[TDE97]

@ChemHead, sorry if this is unrelated, but you mentioned how you reduce your inflammation and itchiness with a change in diet. What were the changes? I have been taking finasteride and Nizoral but they don't seem to help much.

 

[czecha]

@ChemHead, sorry if this is unrelated, but you mentioned how you reduce your inflammation and itchiness with a change in diet. What were the changes? I have been taking finasteride and Nizoral but they don't seem to help much.

He eats a raw vegan diet.
Funnily, eating like this, and fasting in general, causes joint pain in me. While eating lots of starches and meat doesn’t, but comes with more gut/endotoxin/inflammation related problems

if I found a diet that keeps metabolic rate up while not being inflammatory that would be the ideal scenario. A mostly vegetarian Ray peat diet is probably the closest to it

 

[partysnacks]

So I came across this patent today discussing the use of an aromatase inhibitor for hair growth: https://patents.google.com/patent/WO1996008231A1/en

Am I missing something here or does this totally fly in the face of what has been discussed in this thread (and even anecdotal evidence with estradiol gel)? I'm wondering if someone can make sense of it, but I don't want to derail the thread here.
I'm not knowledgeable enough to draw any enlightening insight from this, but I thought it relevant to the thread. Apologies if this is all bunk.

Here's one of the conclusions:

These findings suggest that absence of aromatase activity is an important feature of dermal papilla function and that the maintenance of a "low oestrogen" environment may be necessary for hair growth to proceed.
[...]
It thus follows that treatment with an aromatase inhibitor will reduce or eliminate conversion of testosterone to oestrogen and consequently slow down or even reverse the balding process.

(Also note that they specifically mean a topical aromatase inhibitor.)

Also interesting that it mentions aminoglutethimide, previously reported on here: https://www.hairlosstalk.com/studies/research-studies/aromatase-estrogen-role-hair-growth/.

 

[czecha]

So I came across this patent today discussing the use of an aromatase inhibitor for hair growth: https://patents.google.com/patent/WO1996008231A1/en

Am I missing something here or does this totally fly in the face of what has been discussed in this thread (and even anecdotal evidence with estradiol gel)? I'm wondering if someone can make sense of it, but I don't want to derail the thread here.
I'm not knowledgeable enough to draw any enlightening insight from this, but I thought it relevant to the thread. Apologies if this is all bunk.

Here's one of the conclusions:

(Also note that they specifically mean a topical aromatase inhibitor.)

Also interesting that it mentions aminoglutethimide, previously reported on here: https://www.hairlosstalk.com/studies/research-studies/aromatase-estrogen-role-hair-growth/.

there are lots of patents on anything. most don't produce results
You need to look for results, not patents.

 

[ChemHead]

So I came across this patent today discussing the use of an aromatase inhibitor for hair growth: https://patents.google.com/patent/WO1996008231A1/en

Am I missing something here or does this totally fly in the face of what has been discussed in this thread (and even anecdotal evidence with estradiol gel)? I'm wondering if someone can make sense of it, but I don't want to derail the thread here.
I'm not knowledgeable enough to draw any enlightening insight from this, but I thought it relevant to the thread. Apologies if this is all bunk.

Here's one of the conclusions:

(Also note that they specifically mean a topical aromatase inhibitor.)

Also interesting that it mentions aminoglutethimide, previously reported on here: https://www.hairlosstalk.com/studies/research-studies/aromatase-estrogen-role-hair-growth/.

So, we'll start with the patent... it's over 25 years old and the ideas presented in it are outdated and some of them have long since been proven to be otherwise than stated.

In hair follicles in most body sites, testosterone acts as a pre-hormone and the response to testosterone is determined by which metabolic pathway predominates. In skin sites where 5a - reductase activity is high, such as in the beard, testosterone is metabolised to DHT which has a stimulatory action on hair growth. In scalp, testosterone is metabolised mainly via the aromatase pathway to oestrogens causing inhibition of hair growth. Aromatase activity is under receptor- mediated androgenic control; hence balding does not occur in testicular feminisation. The greater severity of balding in men compared with women can be explained by higher levels of oestrogen being attained in the male scalp by virtue of androgen stimulated aromatase activity. An analogous situation exists in the brain where certain aspects of male behaviours in a number of avian and mammalian species are determined by oestrogens synthesised locally by androgen-dependent aromatisation of androgens [12]. This hypothesis is also able to encompass a role for 5α - reductase; as DHT is a more potent androgen than testosterone, circulating or locally formed DHT can be a more effective inducer of aromatase.

The first part highlighted in this excerpt is precisely the opposite of reality.. based both on what I know, based on more modern research, and also just based on anecdotal evidence. Women that take aromatase inhibitors for breast cancer suffer from hair thinning. I've used an aromatase inhibitor myself... it causes thinning and makes the hairshaft weak and brittle.

The only possible way I could see an aromatase inhibitor being used for hair loss effectively is if there were one made that specifically antagonized only aromatase in the hypothalamus and nowhere else in the body. This would cause an increase in overall steroid synthesis which would be positive for hair growth. This would also be a miracle drug for bodybuilders.

The biggest, easiest flaw I can spot in the patent, though, would be the equivalency of the effects of an aromatase inhibitor on mouse fur with human scalp hair. They're not the same just as human beard hair and scalp hair aren't quite the same (at least beard hair is still human).

The second highlighted part is a true statement and actually has a lot of significance, but it goes completely unrecognized by the researchers. DHT is a potent inducer of aromatase activity because it binds the androgen receptor with high affinity and aromatase activity is regulated in a feedback loop that is positively associated with androgen receptor activation. Because of this, the window of highest effectiveness for finasteride is when 5AR is bound, but there is still a remnant of DHT and the hypothalamus has not yet downregulated steroid synthesis (due to increase in eventual hypothalamic estrogen receptor activation). In this scenario, 5AR is bound by finasteride (so, testosterone is free to be aromatized), but aromatase expression and estrogen receptor expression is still high and, so, the result is higher estrogenic gene expression within the hair follicle. This lasts until aromatase is downregulated by both local and systemic actions. Locally, all that testosterone is now being aromatized rather than 5a-reduced. This would actually be ok if the body continued to synthesize the same amount of testosterone. It doesn't, however, due to hypothalamic regulatory intervention and you end up with less androgen receptor activation within the follicle and, therefore, less aromatase expression. The androgen receptor doesn't need to be bound by DHT to upregulate aromatase... testosterone will do just fine, too. The problem is that when you systemically antagonize 5AR, you cause your body to produce less androgenic steroids overall and this results in less androgenic activity at a local level and less estrogenic activity. And this is why, for some people, finasteride actually makes their hair worse. It's making the original problem (lack of intrafollicular estrogenic activity) worse.

 

[czecha]

So, we'll start with the patent... it's over 25 years old and the ideas presented in it are outdated and some of them have long since been proven to be otherwise than stated.



The first part highlighted in this excerpt is precisely the opposite of reality.. based both on what I know, based on more modern research, and also just based on anecdotal evidence. Women that take aromatase inhibitors for breast cancer suffer from hair thinning. I've used an aromatase inhibitor myself... it causes thinning and makes the hairshaft weak and brittle.

The only possible way I could see an aromatase inhibitor being used for hair loss effectively is if there were one made that specifically antagonized only aromatase in the hypothalamus and nowhere else in the body. This would cause an increase in overall steroid synthesis which would be positive for hair growth. This would also be a miracle drug for bodybuilders.

The biggest, easiest flaw I can spot in the patent, though, would be the equivalency of the effects of an aromatase inhibitor on mouse fur with human scalp hair. They're not the same just as human beard hair and scalp hair aren't quite the same (at least beard hair is still human).

The second highlighted part is a true statement and actually has a lot of significance, but it goes completely unrecognized by the researchers. DHT is a potent inducer of aromatase activity because it binds the androgen receptor with high affinity and aromatase activity is regulated in a feedback loop that is positively associated with androgen receptor activation. Because of this, the window of highest effectiveness for finasteride is when 5AR is bound, but there is still a remnant of DHT and the hypothalamus has not yet downregulated steroid synthesis (due to increase in eventual hypothalamic estrogen receptor activation). In this scenario, 5AR is bound by finasteride (so, testosterone is free to be aromatized), but aromatase expression and estrogen receptor expression is still high and, so, the result is higher estrogenic gene expression within the hair follicle. This lasts until aromatase is downregulated by both local and systemic actions. Locally, all that testosterone is now being aromatized rather than 5a-reduced. This would actually be ok if the body continued to synthesize the same amount of testosterone. It doesn't, however, due to hypothalamic regulatory intervention and you end up with less androgen receptor activation within the follicle and, therefore, less aromatase expression. The androgen receptor doesn't need to be bound by DHT to upregulate aromatase... testosterone will do just fine, too. The problem is that when you systemically antagonize 5AR, you cause your body to produce less androgenic steroids overall and this results in less androgenic activity at a local level and less estrogenic activity. And this is why, for some people, finasteride actually makes their hair worse. It's making the original problem (lack of intrafollicular estrogenic activity) worse.

Fascinating.
I suppose this is why this works:
https://www.hairlosstalk.com/intera...g-minoxidil-or-propecia-great-results.130241/

Taeian's Hair Loss Protocol - TAEIAN

Many have been wanting me to finally write this out in my own words as an article and not just go off of my post to put it together. So finally here it is. There are a million different products shown with benefits to hair. My suggestions, laid out here, are the result of a … Continue reading...

www.taeian.com

What are in general your thoughts on topical Estrogen creme, it's safety profile, synergies etc?
What would a good regimen look like in your eyes, with minimal sides?

Also, would you be interested in joining a private convo on the ray peat forum regarding the mystery hormone? I think you got some screenshots already.

 

[ChemHead]

Fascinating.
I suppose this is why this works:
https://www.hairlosstalk.com/intera...g-minoxidil-or-propecia-great-results.130241/

Taeian's Hair Loss Protocol - TAEIAN

Many have been wanting me to finally write this out in my own words as an article and not just go off of my post to put it together. So finally here it is. There are a million different products shown with benefits to hair. My suggestions, laid out here, are the result of a … Continue reading...

www.taeian.com

What are in general your thoughts on topical Estrogen creme, it's safety profile, synergies etc?
What would a good regimen look like in your eyes, with minimal sides?

Also, would you be interested in joining a private convo on the ray peat forum regarding the mystery hormone? I think you got some screenshots already.

The only thing I can honestly recommend, in terms of chemicals/topical treatments would be ones that have very short half lives (like between seconds to minutes upon entering the blood). This is because the only real way to get good results from any treatment is for the effect to take place only in the hair follicles and nowhere else. Once the rest of the body is affected by your treatment, it causes large systemic changes in steroid concentrations and then the result you're after (increasing intrafollicular estrogenic activity, for example) ends up being negated.

What's looking more and more promising is dietary and lifestyle induced epigenome changes. In other words, finding long-term dietary and lifestyle adjustments that may lead to positive epigenetic changes. Scalp massages are one of those "lifestyle" changes that has been proven in a clinical setting to induce long term epigenetic changes.

As far as a topical goes, I'd say a topical prostaglandin E2 would be worth experimenting with. It has a relatively short half life and it induces higher aromatase expression. So, ideally, if you can introduce it to the scalp and not have to worry about it getting much further throughout the body before it is essentially denatured and can't cause large systemic effects, then it should produce a positive result. Also, for the same reason, ricinoleic acid from caster oil should also induce higher aromatase expression. Both of these work pretty similarly, but I would say that prostaglandin E2 is definitely the more potent of the two.

Whoever develops a potent estrogen receptor agonist that has a very short half life and can be activated locally from outside the body will win a nobel prize. It would be somewhat of a fountain of youth drug for the skin and hair (in both men and women). A pharmaceutical like that is essentially doing what we want.. which is to deploy a very high concentration of an estrogenic compound in a very specific and confined location. This is already how a normal, well-functioning body works. The body deploys a prohormone (like testosterone) which, in high serum concentration, ends up within a cell and then that cell's enzymatic machinery metabolizes it in high concentration to another more specialized steroid. Because those steroids are created on demand and within the cell, you're able to deliver high concentrations of steroids like estradiol and DHT without affecting the body on a systemic level.


Regarding the raypeat forum, if you send me a link to the conversation, I may create an account and join in.

 

[partysnacks]

So, we'll start with the patent... it's over 25 years old and the ideas presented in it are outdated and some of them have long since been proven to be otherwise than stated.



The first part highlighted in this excerpt is precisely the opposite of reality.. based both on what I know, based on more modern research, and also just based on anecdotal evidence. Women that take aromatase inhibitors for breast cancer suffer from hair thinning. I've used an aromatase inhibitor myself... it causes thinning and makes the hairshaft weak and brittle.

The only possible way I could see an aromatase inhibitor being used for hair loss effectively is if there were one made that specifically antagonized only aromatase in the hypothalamus and nowhere else in the body. This would cause an increase in overall steroid synthesis which would be positive for hair growth. This would also be a miracle drug for bodybuilders.

The biggest, easiest flaw I can spot in the patent, though, would be the equivalency of the effects of an aromatase inhibitor on mouse fur with human scalp hair. They're not the same just as human beard hair and scalp hair aren't quite the same (at least beard hair is still human).

The second highlighted part is a true statement and actually has a lot of significance, but it goes completely unrecognized by the researchers. DHT is a potent inducer of aromatase activity because it binds the androgen receptor with high affinity and aromatase activity is regulated in a feedback loop that is positively associated with androgen receptor activation. Because of this, the window of highest effectiveness for finasteride is when 5AR is bound, but there is still a remnant of DHT and the hypothalamus has not yet downregulated steroid synthesis (due to increase in eventual hypothalamic estrogen receptor activation). In this scenario, 5AR is bound by finasteride (so, testosterone is free to be aromatized), but aromatase expression and estrogen receptor expression is still high and, so, the result is higher estrogenic gene expression within the hair follicle. This lasts until aromatase is downregulated by both local and systemic actions. Locally, all that testosterone is now being aromatized rather than 5a-reduced. This would actually be ok if the body continued to synthesize the same amount of testosterone. It doesn't, however, due to hypothalamic regulatory intervention and you end up with less androgen receptor activation within the follicle and, therefore, less aromatase expression. The androgen receptor doesn't need to be bound by DHT to upregulate aromatase... testosterone will do just fine, too. The problem is that when you systemically antagonize 5AR, you cause your body to produce less androgenic steroids overall and this results in less androgenic activity at a local level and less estrogenic activity. And this is why, for some people, finasteride actually makes their hair worse. It's making the original problem (lack of intrafollicular estrogenic activity) worse.

Thanks for the analysis. I figured it was mostly wrong since its contrary to everything I've read as well, but I like these seemingly contrarian ideas as sometimes they can point you in a direction you wouldn't expect (though this case was kind of a bust).

Your last paragraph is great summary of the dilemma.
One aspect I haven't seen mentioned in this thread, maybe I missed it, is 5AR type 1. Do you believe this has any significant role to play? As far as I know, type 1 is only found in scalp skin, not in follicles, so I'm guessing its DHT conversion doesn't matter as much but I haven't seen much confirmation either way.

As far as a topical goes, I'd say a topical prostaglandin E2 would be worth experimenting with.

You mentioned earlier in the thread that you tried hydrolyzing castor oil for the ricinoleic acid - did you have any success with it?

 

[ChemHead]

Thanks for the analysis. I figured it was mostly wrong since its contrary to everything I've read as well, but I like these seemingly contrarian ideas as sometimes they can point you in a direction you wouldn't expect (though this case was kind of a bust).

Your last paragraph is great summary of the dilemma.
One aspect I haven't seen mentioned in this thread, maybe I missed it, is 5AR type 1. Do you believe this has any significant role to play? As far as I know, type 1 is only found in scalp skin, not in follicles, so I'm guessing its DHT conversion doesn't matter as much but I haven't seen much confirmation either way.


You mentioned earlier in the thread that you tried hydrolyzing castor oil for the ricinoleic acid - did you have any success with it?

It's difficult to tell whether type 1 5AR plays a significant role. Clinical in vitro studies would probably suggest that there isn't much of a role, but I wouldn't mind seeing more in vivo literature involving the use of drugs that are highly (near perfectly) selective for only the type 1 enzyme. Finasteride is selective for type 2, but it's not perfect.

I would actually say that, indirectly, any 5AR in the skin within the vicinity of a hair follicle has the potential to draw down testosterone concentration in those areas. I do not think DHT is actually a problem. I think the problem is lack of testosterone (or non-5a-reduced androgen) concentration in the hair follicle combined with possible low aromatase expression. I would say that if you had naturally high serum DHT, but you had little to no intrafollicular expression of 5AR, you would not experience hair loss at all. In fact, I think it would actually make hair growth better because it would likely upregulate aromatase and estrogen receptor expression.

Regarding the ricinoleic acid.. both work, but hydrolyzed works better. However, I'm not sure whether the ricinoleate or the acid form works better. Probably not much of a difference, though.

 

[Dope]

It's difficult to tell whether type 1 5AR plays a significant role. Clinical in vitro studies would probably suggest that there isn't much of a role, but I wouldn't mind seeing more in vivo literature involving the use of drugs that are highly (near perfectly) selective for only the type 1 enzyme. Finasteride is selective for type 2, but it's not perfect.

I would actually say that, indirectly, any 5AR in the skin within the vicinity of a hair follicle has the potential to draw down testosterone concentration in those areas. I do not think DHT is actually a problem. I think the problem is lack of testosterone (or non-5a-reduced androgen) concentration in the hair follicle combined with possible low aromatase expression. I would say that if you had naturally high serum DHT, but you had little to no intrafollicular expression of 5AR, you would not experience hair loss at all. In fact, I think it would actually make hair growth better because it would likely upregulate aromatase and estrogen receptor expression.

Regarding the ricinoleic acid.. both work, but hydrolyzed works better. However, I'm not sure whether the ricinoleate or the acid form works better. Probably not much of a difference, though.

What do you think the cause of PFS is then? Does aromatase expression stay upregulated even once you get off finasteride and how do you fix it?

 

[ChemHead]

What do you think the cause of PFS is then? Does aromatase expression stay upregulated even once you get off finasteride and how do you fix it?

No, aromatase expression is downregulated in PFS. People make the mistake of assuming that their symptoms of PFS are from low DHT and high estrogens. The reality is that their entire body is steroid deprived.. The body is just making less steroids because it's steroid throughput has been decreased by cutting off the 5AR pathway. So, you can go get your testosterone level checked and the number may fall into the the normal category, but that test does not take into consideration total steroid throughput.
In a normally functioning body, prohormones are constantly synthesized and travel through the blood to local areas of enzyme metabolism. As serum steroids are metabolized to specialized steroids, more steroids are being synthesized to replace the ones being metabolized. If you cut off the 5AR pathway (or any enzymatic pathway), you've interrupted that flow.
Think of it this way, imagine a river and a giant valve has been built to control it's rate of flow to keep its levels from rising too high downstream. Now imagine that this large river has a bunch of smaller rivers that branch out from it. Consider what happens when a dam is built before one of the smaller branching rivers and it completely blocks flow to that river and dries it up. The level of the large river and all the other smaller branching rivers will become higher because the dam that was built cut off an avenue for water to flow. So, in order to lower the level of the main river and its branches, that giant valve that controls the flow rate of the main river is adjusted to reduce the flow rate. Now, the water level has returned to normal, but because the flow rate has been reduced, there is less overall throughput of water.
In our bodies, the flowing river is our body's flowing supply of serum steroids, the giant valve is our brain which regulates steroid synthesis and throughput, each junction where the large river branches into a smaller river represents a steroid metabolizing enzyme, and the dam used to block off one of the smaller rivers is an enzyme antagonist (like finasteride).

So, while the "water" level may seem normal, testing the water level does not account for the decrease in flow rate. The level looks normal, but there's less "water" flowing through the system overall.

Regarding the cause of PFS, 5AR expression is one of those things that is involved in its own feedback loop. In other words, the presence of 5AR enzyme is involved in its own genetic expression. Another analogy: in a diesel engine, in order for the engine to turn over, it needs compression inside the cylinders to initiate ignition of the fuel. The ignition then causes the engine to turn over once more which causes the compression of the fuel mixture and then ignition once again and this self sustaining process continues indefinitely. So, the engine's own motion initiates the continuation of that motion. Once it's stopped, it won't start again without a "push".

Finasteride, in those who experience PFS, has permanently bound all or nearly all of their 5AR enzyme and caused genetic senescence. The body likely doesn't have clear instructions on the synthesis of the enzyme and it's not receiving the signals required to initiate that synthesis because the presence of that enzyme is required for its continued synthesis.

This is what I believe the root cause of PFS is.

 

[Selb]

No, aromatase expression is downregulated in PFS. People make the mistake of assuming that their symptoms of PFS are from low DHT and high estrogens. The reality is that their entire body is steroid deprived.. The body is just making less steroids because it's steroid throughput has been decreased by cutting off the 5AR pathway. So, you can go get your testosterone level checked and the number may fall into the the normal category, but that test does not take into consideration total steroid throughput.
In a normally functioning body, prohormones are constantly synthesized and travel through the blood to local areas of enzyme metabolism. As serum steroids are metabolized to specialized steroids, more steroids are being synthesized to replace the ones being metabolized. If you cut off the 5AR pathway (or any enzymatic pathway), you've interrupted that flow.
Think of it this way, imagine a river and a giant valve has been built to control it's rate of flow to keep its levels from rising too high downstream. Now imagine that this large river has a bunch of smaller rivers that branch out from it. Consider what happens when a dam is built before one of the smaller branching rivers and it completely blocks flow to that river and dries it up. The level of the large river and all the other smaller branching rivers will become higher because the dam that was built cut off an avenue for water to flow. So, in order to lower the level of the main river and its branches, that giant valve that controls the flow rate of the main river is adjusted to reduce the flow rate. Now, the water level has returned to normal, but because the flow rate has been reduced, there is less overall throughput of water.
In our bodies, the flowing river is our body's flowing supply of serum steroids, the giant valve is our brain which regulates steroid synthesis and throughput, each junction where the large river branches into a smaller river represents a steroid metabolizing enzyme, and the dam used to block off one of the smaller rivers is an enzyme antagonist (like finasteride).

So, while the "water" level may seem normal, testing the water level does not account for the decrease in flow rate. The level looks normal, but there's less "water" flowing through the system overall.

Regarding the cause of PFS, 5AR expression is one of those things that is involved in its own feedback loop. In other words, the presence of 5AR enzyme is involved in its own genetic expression. Another analogy: in a diesel engine, in order for the engine to turn over, it needs compression inside the cylinders to initiate ignition of the fuel. The ignition then causes the engine to turn over once more which causes the compression of the fuel mixture and then ignition once again and this self sustaining process continues indefinitely. So, the engine's own motion initiates the continuation of that motion. Once it's stopped, it won't start again without a "push".

Finasteride, in those who experience PFS, has permanently bound all or nearly all of their 5AR enzyme and caused genetic senescence. The body likely doesn't have clear instructions on the synthesis of the enzyme and it's not receiving the signals required to initiate that synthesis because the presence of that enzyme is required for its continued synthesis.

This is what I believe the root cause of PFS is.

Off-topic but what can upregulate aromatase expression? And can this be targeted to the scalp?

 

[ChemHead]

Off-topic but what can upregulate aromatase expression? And can this be targeted to the scalp?

PGE2, and ricinoleic acid are good at aromatase induction. Dexamethasone and tetradecanoyl phorbol acetate (TPA) are also strong upregulators of aromatase, but I would stick to more natural things that have very short half lives. Drugs are designed to have longer half lives and this will cause greater systemic activity.

PGE2 and ricinoleic acid will still have systemic effects, just less due to the rapid half lives. PGE2, for example will give me a headache for a couple hours after application. If I remember correctly, I also get a warming tingling sensation. The problem with all treatments still remains, though... You need the activity to occur in the hair follicle and nowhere else to avoid interrupting the body's regulatory feedback loops.

 

[Harleyj888]

I have to reiterate that many people have naturally low aromatase expression in the skin and hair and are much more susceptible to hair loss. Whether this is due to simply having genetically lower expression or due to a lack of enzymes that metabolize estrogens for elimination (causing lower aromatase expression), I'm not sure. There are plenty of guys out there that are able to run steroid cycles that are relatively unaffected by them regarding hair and it's because they have higher aromatase expression and lower 5AR expression. If one of them were to really pay attention to their hair and document changes while on cycle, I would not be surprised if they noticed a little decrease in the thickness of their hair... especially while using an aromatase inhibitor or a SERM.

So, there are really quite a lot of paradoxical things that are going on with hair loss and because of this, as a whole, the community of biochemists and clinical researchers working on it don't have a clear view of what causes it and we end up with drugs that will never really work. A drug that targets 5AR (unless its action is 100% local to the skin and hair follicle) will take care of DHT binding the androgen receptor, but will ultimately downregulate aromatase. A drug that targets the androgen receptor (an androgen receptor antagonist) will also take care of DHT binding the androgen receptor, but this will also down regulate aromatase expression because binding of the androgen receptor causes expression of aromatase to increase. So, what happens is that both of these types of drugs will work for a short time (some longer than others) and then the body will adjust its aromatase expression and they are no longer effective.

People wonder why they begin to shed when using finasteride or RU58841 after awhile and this is the exact reason.. it's not part of the "phases" of the drug doing its magic.. it's because aromatase has been downregulated.. and riding out the storm by continuing to take the drug is not going to improve things. It's done. Aromatase expression has been lowered and the only way to get it back up is from the appropriate androgens binding the androgen receptor (probably in the hypothalamus, but there's also evidence that binding androgen receptors locally causes an increase in aromatase expression). I believe that FSH is responsible for a systemic increase in aromatase expression, but I'm not sure how because there's really not a whole lot of clinical research on FSH. It think that if someone taking finasteride were to take FSH, their aromatase expression would increase, but I also think it wouldn't be healthy.. there's a reason why the aromatase expression was downregulated to begin with.

How do you explain the studies showing 80-90% of people showing improvements or atleast maintenance in hair density and count when taking finasteride after 1-2 years, most people ride out the shed and then notice significant improvements after a year on finasteride, not 2-3 weeks

 

[Dope]

No, aromatase expression is downregulated in PFS. People make the mistake of assuming that their symptoms of PFS are from low DHT and high estrogens. The reality is that their entire body is steroid deprived.. The body is just making less steroids because it's steroid throughput has been decreased by cutting off the 5AR pathway. So, you can go get your testosterone level checked and the number may fall into the the normal category, but that test does not take into consideration total steroid throughput.
In a normally functioning body, prohormones are constantly synthesized and travel through the blood to local areas of enzyme metabolism. As serum steroids are metabolized to specialized steroids, more steroids are being synthesized to replace the ones being metabolized. If you cut off the 5AR pathway (or any enzymatic pathway), you've interrupted that flow.
Think of it this way, imagine a river and a giant valve has been built to control it's rate of flow to keep its levels from rising too high downstream. Now imagine that this large river has a bunch of smaller rivers that branch out from it. Consider what happens when a dam is built before one of the smaller branching rivers and it completely blocks flow to that river and dries it up. The level of the large river and all the other smaller branching rivers will become higher because the dam that was built cut off an avenue for water to flow. So, in order to lower the level of the main river and its branches, that giant valve that controls the flow rate of the main river is adjusted to reduce the flow rate. Now, the water level has returned to normal, but because the flow rate has been reduced, there is less overall throughput of water.
In our bodies, the flowing river is our body's flowing supply of serum steroids, the giant valve is our brain which regulates steroid synthesis and throughput, each junction where the large river branches into a smaller river represents a steroid metabolizing enzyme, and the dam used to block off one of the smaller rivers is an enzyme antagonist (like finasteride).

So, while the "water" level may seem normal, testing the water level does not account for the decrease in flow rate. The level looks normal, but there's less "water" flowing through the system overall.

Regarding the cause of PFS, 5AR expression is one of those things that is involved in its own feedback loop. In other words, the presence of 5AR enzyme is involved in its own genetic expression. Another analogy: in a diesel engine, in order for the engine to turn over, it needs compression inside the cylinders to initiate ignition of the fuel. The ignition then causes the engine to turn over once more which causes the compression of the fuel mixture and then ignition once again and this self sustaining process continues indefinitely. So, the engine's own motion initiates the continuation of that motion. Once it's stopped, it won't start again without a "push".

Finasteride, in those who experience PFS, has permanently bound all or nearly all of their 5AR enzyme and caused genetic senescence. The body likely doesn't have clear instructions on the synthesis of the enzyme and it's not receiving the signals required to initiate that synthesis because the presence of that enzyme is required for its continued synthesis.

This is what I believe the root cause of PFS is.

Thanks. What do you think is the best way to reverse that to push the body out of that with proper signaling?