PFS - Down-regulating Androgen Receptors with DHT

[Dehdly]

Sounds like Glycine, L-Cartinine and Creatine should be my best friends!

I did some digging and found this interest excerpt:

“In order to bolster a particular pathway, cells can increase the amount of a necessary (rate-limiting) enzyme or use activators to convert that enzyme into an active conformation. Conversely, to slow down or halt a pathway, cells can decrease the amount of an enzyme or use inhibitors to make the enzyme inactive.

Such up- and down-regulation of metabolic pathways is often a response to changes in concentrations of key metabolites in the cell. For example, a cell may take stock of its levels of intermediate metabolites and tune the glycolytic pathway and the synthesis of glucose accordingly.”

Source: Cell Metabolism

It seems as though the cell (and specifically the cell) can take stock of the substrates available for certain metabolic pathways, therefore it would seem that the best way to upregulate 5ar activity would be get as much testosterone into cells as possible.

I wonder what metabolic pathways oppose 5ar other than Aromatase as like you said, the body could have established a new homeostasis, therefore the cell says to itself “well we don’t need to make much 5ar as we’ve already created all the DHT we‘re now used to making” so it sends it all off down the aromatase pathway. Therefore by removing every other metabolic pathway, the cell would be forced to create 5ar to metabolise the testosterone??

However issue with that thought is, whether the cell even lets the test into the cell to be metabolised, as it might now be used to not needing that much test as it doesn’t need that much DHT - think it’s called osmosis (the management of infra/extra cell concentrations).

Also going to look into how Glycine/L-Cartinine and Creatine boost 5ar upregulation, as if I can understand that mechanism I might be able to maximise the efficiency or find other substances that do it even better.

 

[EustaceBagge]

Testosterone can only be converted into estrogen and dht, so you would only need to oppose aromatase.

"Therefore by removing every other metabolic pathway, the cell would be forced to create 5ar to metabolise the testosterone??"
This is the idea, the finasteride should have made you estrogen dominant which is of course suboptimal, but still possible as seen by prostate cancer patients also using 5AR inhibitors. We want to change the homeostasis into a more androgenic one, and that is only possible through making the body understand there is not enough estrogen to go by for its current homeostasis.

"However issue with that thought is, whether the cell even lets the test into the cell to be metabolised, as it might now be used to not needing that much test as it doesn’t need that much DHT - think it’s called osmosis (the management of infra/extra cell concentrations)."
This is extremely deep, but i doubt hormones are used for osmosis. Body has seperate proteins and mechanisms for that. By your logic the body can also not make estrogen, but right now your clearly estrogen dominant.

"Also going to look into how Glycine/L-Cartinine and Creatine boost 5ar upregulation, as if I can understand that mechanism I might be able to maximise the efficiency or find other substances that do it even better."
L-Carnitine basically shuttles fats into cells and is not needed if you eat enough saturated fats in your diet tbh. The other 2 are pretty solid, especially creatine which you can basically use for the rest of your life especially if your into weightlifting. Glycine is beneficial because the current emphasis on muscle meats makes us deficient in glycine even though your body produces it on its own. Glycine is found in bones/tendon/skin/organ meats, hence its high content in bone broth.

43 best ways to increase DHT (2023 update) » TESTONATION

I'm going to show you how to increase DHT (our strongest androgen) with many dietary, lifestyle and supplemental tricks.

men-elite.com

Hans Amato's article on how to boost 5AR (and thus DHT). Much more indepth.

Also look at this thread:

PFS: 3a and 3b-HSD theory

In this Friday's newsletter, I postulated the theory that it might not necessarily be the 5-AR type 1 or 2 enzymes that are defective, but rather 3a and 3b-HSD. I quote from the newsletter: "Most people think that PFS is caused by downregulated 5AR, but a lot of people actually have normal DHT...

raypeatforum.com

The proposed solution there is easier, and if it doesnt work you can take more drastic measures like you do rn. Difficult issue.

 

[Dehdly]

"Why do you think that aromatase inhibition doesn’t fix PFS for everyone?"
I honestly do not know, but there is no sure fix for PFS people, and it might have to do with the fact that there is not enough of a shock to the body in the form of a supraphysiological dose of test.

"I’m still wondering how 5ar enzymatic activity is down regulated by Finasteride. From what I’ve read 5ar is present in high quantities in skin cells therefore topical applications are more androgenic, however is it that the 5ar enzymes are just dormant waiting for a viable substrate? Or, is it that they are genuinely non existent and we need to kickstart our gene transcription process to create more?"
I'm not sure about this one either, but we can safely assume nothing is wrong with the androgen receptors themselves because even though finasteride shuts down DHT, it doesn't touch testosterone and they both go to the same receptors. If your body establishes a new homeostasis in a DHT low enviroment the need for 5AR might decrease I guess? How the body will react to a low estrogen high testosterone enviroment is beyond me, but it seems logical that it might shift homeostasis to a more androgen dependent state.

"Do you know if there is any literature on the creation of 5ar enzymes that you’ve read and consider worth reading? I don’t exactly want to delve into a massive endocrinology book, but maybe just the sections of 5ar enzymatic activity and creation."
I don't have anything worthwile as a single exhaustive part, but I know that for example some compounds mess up androgen receptor sensitivity, and some compounds mess with DHT synthesis by inhibiting 5AR. I can list a couple of them:

High doses of Zinc, high doses of vitamin E, high doses of B6, most herbs etc.

Then there are compounds that upregulate 5AR or increase androgen receptors, 3 worthwhile ones:
Glycine
L-Carnitine
Creatine

There are even studies showing vitamin K2 inhibits androgen receptor expression in prostate cancer cells, just like vitamin E does: Vitamin K2, a Naturally Occurring Menaquinone, Exerts Therapeutic Effects on Both Hormone-Dependent and Hormone-Independent Prostate Cancer Cells

So in general, most compounds are NOT good to be deficient in, but also NOT good in excess. Your best bet is to keep diet clean, high in meat, high in dairy, some glycine/bone broth, some creatine, high in saturated fats. If your going to eat vegetables cook them well and fruit is ok.

Even though coffee is generally androgenic I would for the time being not rely on any plant based compounds cuz they always seem to mess with androgen signalling in some way or another. Caffeine in isolated form is ok.

Just purchased Arimidex 1mg tablets and 500g Glycine - I already take Creatine for working out.

If this doesnt work then i'll look at testosterone supplementation.

If test doesn't work, then i'll look into 3a / 3b HSD

If this doesnt work then I have absolutely no idea!

 

[EustaceBagge]

Best of luck

 

[Dehdly]

Best of luck

Thanks for all your help ??

 

[Mister]

@Dehdly Keep us up to date

 

[Dehdly]

@Dehdly Keep us up to date

Update: @Mister @EustaceBagge

I have received the Glycine, used 4G tonight at 10:30pm and feeling rather relaxed and sleepy. Interested to see if there are dramatic effects when taking Glycine and if results are proportional with respect to an increase in dosage (ie - the more you take the more sedated you get).

Arimidex has been shipped and likely to reach me in a few days. I will be continuing with the DHT & HCG supplementation until all 10 grams of DHT have been used. During an experiment using 100% DMSO, I have found the solubility of pure DHT (Stanolone) powder to be 130mg/ml
- a far cry from 58mg/ml stated on some pharmaceutical websites.

Once DHT has been exhausted I am cutting off cold turkey to begin Arimidex. I am worried about the side effects of doing this - any advice would be appreciated.

In my experience, DHT has helped me mentally. Physically you could say it’s defined me a bit more, but not so you’d notice.
As expected from a predominant neurosteriod, the effects of DHT have been positive but only with respect to mental cognition, memory, drive and overall mood. It’s not eurphoric, just rather controlled calmness with a tinge of heightened anxiety.

 

[EustaceBagge]

Only side effect I see of going cold turkey on your current protocol is that you may have been shutdown, so that if you stop your DHT & HCG supplementation it might take a while before you start your own production again. It all depends on how shutdown you are. Otherwise everything should be ok. Make sure you don't get low estrogen side effects but don't be afraid to up the dose, worst case you just drop down the dose again and wait 2 weeks before you normalize.

Nothing to worry about, but patience will be needed.

And yes, glycine is known for making you less stressed so its best taken before bed.

 

[Motorneuron]

"Why do you think that aromatase inhibition doesn’t fix PFS for everyone?"
I honestly do not know, but there is no sure fix for PFS people, and it might have to do with the fact that there is not enough of a shock to the body in the form of a supraphysiological dose of test.

"I’m still wondering how 5ar enzymatic activity is down regulated by Finasteride. From what I’ve read 5ar is present in high quantities in skin cells therefore topical applications are more androgenic, however is it that the 5ar enzymes are just dormant waiting for a viable substrate? Or, is it that they are genuinely non existent and we need to kickstart our gene transcription process to create more?"
I'm not sure about this one either, but we can safely assume nothing is wrong with the androgen receptors themselves because even though finasteride shuts down DHT, it doesn't touch testosterone and they both go to the same receptors. If your body establishes a new homeostasis in a DHT low enviroment the need for 5AR might decrease I guess? How the body will react to a low estrogen high testosterone enviroment is beyond me, but it seems logical that it might shift homeostasis to a more androgen dependent state.

"Do you know if there is any literature on the creation of 5ar enzymes that you’ve read and consider worth reading? I don’t exactly want to delve into a massive endocrinology book, but maybe just the sections of 5ar enzymatic activity and creation."
I don't have anything worthwile as a single exhaustive part, but I know that for example some compounds mess up androgen receptor sensitivity, and some compounds mess with DHT synthesis by inhibiting 5AR. I can list a couple of them:

High doses of Zinc, high doses of vitamin E, high doses of B6, most herbs etc.

Then there are compounds that upregulate 5AR or increase androgen receptors, 3 worthwhile ones:
Glycine
L-Carnitine
Creatine

There are even studies showing vitamin K2 inhibits androgen receptor expression in prostate cancer cells, just like vitamin E does: Vitamin K2, a Naturally Occurring Menaquinone, Exerts Therapeutic Effects on Both Hormone-Dependent and Hormone-Independent Prostate Cancer Cells

So in general, most compounds are NOT good to be deficient in, but also NOT good in excess. Your best bet is to keep diet clean, high in meat, high in dairy, some glycine/bone broth, some creatine, high in saturated fats. If your going to eat vegetables cook them well and fruit is ok.

Even though coffee is generally androgenic I would for the time being not rely on any plant based compounds cuz they always seem to mess with androgen signalling in some way or another. Caffeine in isolated form is ok.

I don't think I get it right as it appeared that K2 was PRO androgenic and had anti aromatase properties.

Do you claim that it is exactly the opposite?

 

[EustaceBagge]

I don't think I get it right as it appeared that K2 was PRO androgenic and had anti aromatase properties.

Do you claim that it is exactly the opposite?

Not the exact opposite, but there are studies showing it reduces androgen receptor signalling, just like vitamin E does.

Progesterone is androgenic up until a certain point, same with k2 and vitamin E.

Vitamin K2, a Naturally Occurring Menaquinone, Exerts Therapeutic Effects on Both Hormone-Dependent and Hormone-Independent Prostate Cancer Cells

In recent years, several studies have shown that vitamin k2 (VK2) has anticancer activity in a variety of cancer cells. The antitumor effects of VK2 in prostate cancer are currently not known. In the present study, we sought to characterize the anticancer ...

www.ncbi.nlm.nih.gov

Androgen receptor expression in LnCAP cells was reduced significantly with K2 supplementation.

Vitamin E succinate inhibits the function of androgen receptor and the expression of prostate-specific antigen in prostate cancer cells - PubMed

Although epidemiological evidence indicates that a daily supplement of vitamin E may reduce the risk of prostate cancer, the detailed mechanism underlying this effect remains unclear. Here we demonstrate that alpha-tocopheryl succinate (VES) can suppress the expression of prostate-specific...

pubmed.ncbi.nlm.nih.gov

Same with vitamin E.

Haidut post about E:

Vitamin E (tocopherol) Is A Potent Aromatase Inhibitor

Hi all, As you know Ray has written extensively on the benefits of Vitamin E though its actions as an estrogen antagonist. I opsted some studies that show that tocopherols act directly like estrogen "receptor" antagonist and this may explain some of their anti-estrogenic properties. However...

raypeatforum.com

"This would make vitamin E even more attractive substance for Peat-minded people since reducing estrogen (AKA the "shock hormone") is one of the main goals of the Peat-style diets and regimens. Interestingly, tocopherols were also found to suppress androgen signaling WITHOUT suppressing androgen metabolism. So, what other substance is known to have this effect - i.e. estrogen receptor antagonist, aromatase inhibitor, and anti androgenic? The answer is - progesterone!"

I may be drawing conclusions based on too few data, but this shows clearly to me that K2, which reduces androgen receptor signalling, may just as well be androgenic as estrogenic depending on dose. If anyone here follows a Peaty diet I don't think that person will be deficient in K2.

 

[tallglass13]

This makes so much sense! I wonder how long it will take for my estrogen levels to drop and 5ar to pick up the extra testosterone? I need to do this for long enough for the positive 5ar feedback mechanism to fully establish itself.

Why do you think that aromatase inhibition doesn’t fix PFS for everyone? If it was just as easy as not allowing testosterone to aromatise, then would everyone not just be fixed after taking AIs for a long enough time?

I’m still wondering how 5ar enzymatic activity is down regulated by Finasteride. From what I’ve read 5ar is present in high quantities in skin cells therefore topical applications are more androgenic, however is it that the 5ar enzymes are just dormant waiting for a viable substrate? Or, is it that they are genuinely non existent and we need to kickstart our gene transcription process to create more?

I think the science behind how to actually CREATE more 5ar enzymes is the key here as no matter what substrate concentration we provide the ideal metabolic path cannot be realised without 5ar itself.

Therefore I see this as two parts:

1 - Creation of 5ar enzymes or upregulation of dormant enzymes (which ever it turns out to be)

2 - Availability of substrate concentrations to feed the 5ar process.

Also, the substrates won’t just be testosterone, but all the 5ar metabolic pathway precursors like progesterone, androstenedione, epitestosterone, cortisol, aldosterone, and deoxycorticosterone. And as I’m sure you can appreciate, no chance of supplementing all of these separately.

Do you know if there is any literature on the creation of 5ar enzymes that you’ve read and consider worth reading? I don’t exactly want to delve into a massive endocrinology book, but maybe just the sections of 5ar enzymatic activity and creation.

From what I understand, Finasteride destroys the Liver 5 alpha reductase gene expression, thus the very creation of the liver enzyme 5ar is impaired.

 

[Dehdly]

From what I understand, Finasteride destroys the Liver 5 alpha reductase gene expression, thus the very creation of the liver enzyme 5ar is impaired.

Do you have any studies or other official literature to support that statement?

 

[tallglass13]

Do you have any studies or other official literature to support that statement?

How about using 5-alpha reductase inhibitor Finasteride to regrow hair? When Finasteride kills the 5-alpha reductase gene expression in your pituitary glands and testicles and the liver 5-alpha reductase release, Finasteride tends to increase testosterone and estrogen( for breast growth!) but severely deplete DHT in the penile tissue, brain and bones after damaging the 5-alphase reductase gene and DNA in the liver, bone, testicles, penis, and of course, brain. Please read " On the role of DHT in the penile Growth, Repair (Re-Growth) and structure for more sexual orgasm.
==>" "Testosterone down-regulates the levels of androgen receptor mRNA in smooth muscle cells from the rat corpora cavernosa via aromatization to estrogens - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8499343, " and " Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8723114 ," and " Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat -
Endocrine Press ." The gene/DNA destruction is very difficult to reverse. The only hope you can have is to excite the prostaglandin E-1, NO and oxytocin for the 5-alpha reductase gene/DNA repair. Please beware that it may take about 3-6 months to excite the NOergic and Oxytocinergic nervous system in your brain, liver and testicles/penis after the liver is detoxified. Don't expect any miracles from our products when your 5-alpha reductase gene/DNA is destroyed! Our products can work up to 90% efficiency/effectiveness for the Finasteride destruction cases according to our statistics. You must be aware that there is about 10% chance our products won't work if the 5-alpha reductase gene/DNA in your testicles is destroyed by Finasteride! This mean the damage of 5-alpha reductase gene and DHT receptors is too extensive for rejuvenation and repair, respectively, among the 10% of the Finasteride victims. We offer you a hope to revive your liver and pituitary-testicular function and penile erection, but we cannot guarantee your sex life at all. You are responsible for the consequence of taking this most destructive 5-alpha reductase inbibitor drug. If you have a weak erection, the formula mentioned above can help you. If you have become impotent by Finasteride for sometimes, please have a serum DHT test and if your serum DHT level is below 30 ng/dl, please don't order our products.
Warning: Prostate Cancer Treatment with Androgen (DHT) suppression therapy Can Speed Heart Attacks due to the fact that it can cause anemia, increase body fat, reduce muscle, increase harmful LDL cholesterol and decrease helpful HDL cholesterol, according to the June 10, 2007 issue of the Journal of Clinical Oncology. Finasteride is a DHT suppressor too.

 

[tallglass13]

Finasteride blocks the liver's 5-alpha reductase release and damages the 5-alpha reductase genes in the testicules, brains and other organs to reduce or stop the testosterone-DHT conversion in order to elevate the testosterone level to grow hair. The most critical problem is the liver damage and the stimulation of the liver to release aromatase for the testosterone-estrogen (estradiol) conversion to grow the breasts and to shrink the penis and testicles.
testosterone grows hair while DHT and stress neurohormone epinephrine cause hair loss. DHT alone won't cause hair loss since puberty boys grows hair with a high level of testosterone and DHT without stress.
When men get older, testosterone and DHT drops but the stress neurohormone epinephrine release from adrenal medullar increases, so that the middle-aged and senior men lose their hair and shrink the penis.
When excessive epinephrine is bound into the sympathetic nervous alpha receptors in the blood vessels, the blood vessels constrict and the blood circulation become very poor. The blood circulation of the thin scalp is almost interrupted and it traps too much DHT in hair root cells which starve to die due to a lack of fresh blood with oxygen, testosterone and nutrients.
This means DHT alone won't cause hair loss since the puberty boy's DHT production reaches the peak of the male life and the hair growth is faster than any age of the male life.
Over-masturbation or over-ejaculation induces chronically excessive dopamine/norepinephrine-epinephrine conversion in the adrenal medulla, in additional to the testosterone-DHT conversion.
When Finasteride shut down your testosterone-DHT conversion and reduce your sexual function (including semen production), your hair will regrow again.
But now, you have to struggle with your liver and testicular functional disorders. You won't get a full recovery when the 5-alpha reductase genes in the liver and testicles are damaged.

 

[CloudsInTheHead]

From what I understand, Finasteride destroys the Liver 5 alpha reductase gene expression, thus the very creation of the liver enzyme 5ar is impaired.

Given that most PFS suffers have normal serum DHT levels, and serum DHT is mostly synthesized in the liver, I find that unlikely.

 

[tallglass13]

Given that most PFS suffers have normal serum DHT levels, and serum DHT is mostly synthesized in the liver, I find that unlikely.

I find it unlikely you have seen plenty of actual labs for DHT serum and free DHT. Anything under 30ng is a problem. You need your body to produce up to 50-60 ng for good erection performance . Also from the scientist above that I referenced, he stated high Estrogen makes DHT insensitive, so you can have normal DHT and it not working very well. There is no debate about Finasteride disrupting a persons DHT production, so why do you find it unlikely that the Poison of Finasteride disables the livers production of DHT? That is what is supposed to do. People can also re-generate , but some people may have more difficulty than others.

 

[EustaceBagge]

Finasteride blocks the liver's 5-alpha reductase release and damages the 5-alpha reductase genes in the testicules, brains and other organs to reduce or stop the testosterone-DHT conversion in order to elevate the testosterone level to grow hair.

Given that most PFS suffers have normal serum DHT levels, and serum DHT is mostly synthesized in the liver, I find that unlikely.

It is possible that 5AR is significantly impaired, but strange that it is only apparent in some tissues. If there is not evidence it clearly sabotages 5AR in the brain as compared to other organs etc. I find it hard to believe the effects are not systemic and evenly spread out according to the density of 5AR receptors.

The most critical problem is the liver damage and the stimulation of the liver to release aromatase for the testosterone-estrogen (estradiol) conversion to grow the breasts and to shrink the penis and testicles.

At least this supports the idea of using an aromatase inhibitor. The body relies either on androgenic hormones or estrogenic hormones, but never do you have a homeostasis involving the dominance of both (impossible). So lets force a shift by inhibiting aromatase.



And if I may ask, what is your idea of reversing PFS because I've heard a lot of success stories with a lot of different methods and you seem fixated on the liver which is new to me. I would like to hear your idea in more detail as in how to fix the issue.

 

[tallglass13]

It is possible that 5AR is significantly impaired, but strange that it is only apparent in some tissues. If there is not evidence it clearly sabotages 5AR in the brain as compared to other organs etc. I find it hard to believe the effects are not systemic and evenly spread out according to the density of 5AR receptors.


At least this supports the idea of using an aromatase inhibitor. The body relies either on androgenic hormones or estrogenic hormones, but never do you have a homeostasis involving the dominance of both (impossible). So lets force a shift by inhibiting aromatase.



And if I may ask, what is your idea of reversing PFS because I've heard a lot of success stories with a lot of different methods and you seem fixated on the liver which is new to me. I would like to hear your idea in more detail as in how to fix the issue.

This is all the work of Dr. Newman, who is a scientist. However, you have to treat the body as whole system and not just liver, although the liver is central in producing the 5ar enzymes. However, all different areas of the body produce 5 ar enzyme like the brain and skin, testicles. Finasteride affects all of them. In what degree, is most likely individual. I believe you can always reverse issues with the body. Using liver detox herbs and cleansing the bile and getting it moving is a start. Getting the best nutrition, like this MD recommends lots of seafood, and herbs to increase NO , and upgrading Prostaglandin E1-E3 series.

 

[CloudsInTheHead]

I find it unlikely you have seen plenty of actual labs for DHT serum and free DHT. Anything under 30ng is a problem. You need your body to produce up to 50-60 ng for good erection performance . Also from the scientist above that I referenced, he stated high Estrogen makes DHT insensitive, so you can have normal DHT and it not working very well. There is no debate about Finasteride disrupting a persons DHT production, so why do you find it unlikely that the Poison of Finasteride disables the livers production of DHT? That is what is supposed to do. People can also re-generate , but some people may have more difficulty than others.

The first thing every PFS sufferer checks is their serum DHT, and most of the time it's fine; if the problem were that simple, it would be nearly trivial to treat.

My DHT about tripled after quitting. There's just no evidence for what you're claiming.

 

[tallglass13]

The first thing every PFS sufferer checks is their serum DHT, and most of the time it's fine; if the problem were that simple, it would be nearly trivial to treat.

My DHT about tripled after quitting. There's just no evidence for what you're claiming.

You are to simple obviously. What the heck do you think Finasteride does to the body? There is no debate that it disrupts the gene expression 5 ar enzymes throughout the body. This is not a thought of mine HeadintheClouds, This is what was learnt through the work of science. I don't really care what you think actually , but some find it interesting and can further educate and look down different avenues because of Dr. Newmans work.