Anonymous user's theory: DHT treatment to increase 5AR2 expression


#1

[i]All,

I received the following emails from an anonymous user, and have posted the correspondence for us all. [/i]


ANONYMOUS EMAIL:

I have been reading this forum for insight as to the cause of finasteride induced hypogonadal hypogonadism. The studies in OTHER STUDIES section are very informative.

Lets start with the facts:

  1. all of the men had normal sexual function prior to the finasteride treatment, and DHT is responsible for prostate growth

  2. studies show DHT is responsible for NO synthesis and release, and erectile function – you posted this in other studies 11/02/06:
    propeciahelp.com/forum/viewtopic.php?t=64
    propeciahelp.com/forum/viewtopic.php?t=65

  3. finesteride halts gene expression mRNA synthesis of 5AR in the prostrate and the anterior pituitary — see study on DHT and GnRh regulation (you posted this on 12/27/06 in OTHER STUDIES): propeciahelp.com/forum/viewtopic.php?t=171

4)finesteride decrease weight of prostate and PROBABLY the anterior pituitary too – see same study: propeciahelp.com/forum/viewtopic.php?t=171

5)finesteride doubled the concentration of testosterone in the prostate. The author states these changes probably occur in the anterior pituitary as well… really read this study! Page 1041, exp. 2, 2nd paragraph, 9th line — endo.endojournals.org/cgi/reprint/139/3/1038.pdf

  1. somehow after finesteride treatment men get fixed in a state where the pituitary is insensitive to low testosterone

Now here is my theory:

  1. Since finesteride raised testosterone levels in the prostate, and the author extrapolates this to the anterior pituitary as well, then finesteride shrinks the 5AR producing part of the pituitary.

  2. This halts the conversion of testosterone to DHT within the pituitary.

  3. This raises the concentration of testosterone in the pituitary and maybe even the hypothalamus.

  4. As a result, the pituitary thinks the serum testosterone is high or normal, so no more LH is secreted.

  5. So now we have testosterone backed up (elevated) in the pituitary and the finesteride user has a fixed state of pituitary insensitivity to low serum testosterone!

  6. This would lead to the variability between finesteride users depending how low their 5AR concentration is in the pituitary.

  7. Next, the prostate has lost its ability to make DHT due to same mechanism – so you get impotence.

  8. You may argue that most post finesteride users can make DHT, but the key here is testosterone levels in the prostate and pituitary are raised.

My theory is the 5AR1 in the skin and other organs synthesizes the remaining DHT, but the pituitary and prostate contain 5AR2 which has been downregulated by finesteride – so the finesteride user becomes hypogonadal and has a prostate and erectile tissue that does not release NO… that is why TRT doesnt really help.

Also, this theory explains why clomid may raise testosterone, because although the pituitary is still sensitive to low estrogen it is the lack of 5AR2 in the prostate and pituitary that must be raised.

*** Now here is the CURE! ***

Look at dynaaminen’s post 3/30/07: propeciahelp.com/forum/viewt … ight=#1702

DHT positively upregulates the gene expression of 5AR in the prostate, and probably in the pituitary. These rats were given 1mg/kg dht for 4 days and their prostates size grew more than double, and their 5AR activity was raised about half as much as testosterone (but test raised it 20 times).

so, this would explain why ex finasteride users can get better on their own – the more DHT they make, they slowly reverse the process. They increase 5AR in the pituitary so more testosterone converts to DHT in the pituitary, and the pituitary testosterone level drops and LH goes gradualyy up. The same thing happens in the prostate and erectile tissue, so problems resolve.

But what if some supraphysiologic dose of DHT is given for four days and all of the 5AR is is permanantly increased in the pituitary and prostate? The man would be cured.

This is my proposal, send this email to MEW and discuss with him and keep me anonymous. We then should approach Dr. Shippen to design a treatment protocol using DHT at supraphysiologic dosages for a short time. He can recruit many of the sufferers and do some trials and gather data to fine tune the dose and schedule.

This way everyone is treated for this under a physician’s care and when people come out of the woodwork and get cured, then people will come forward and get this drug off the market.

I have already googled use of DHT in hypogonadism… it doesnt seem to be as negative on the pituitary, so maybe you need HCG or clomid or maybe nothing. There is Intramuscular, transdermal and sublingual – sublingual seems to drop off quick, so there’s little effect on the HPTA but it can create a significant plasma rise and possible stimulate prostate and pituitary 5AR mRNA repair.

This email is not meant to medical advice and is only for discussion with a licensed physician. This is the only theory that fits all the observations and is consistant with the effects of finasteride. I am very optimistic. I will not post and will only communicate with you or mew.


MY (Mew’s) REPLY:

Hello,

Thank you for your email. First of all, who are you, what is your background/education, etc? What is your history with the drug, are you a sufferer yourself? If not, what got you interested in trying to solve this puzzle? How long have you been reading the forum? And why are you unwilling to post and share your theory with others on the forum? I think it would be very helpful for others to read and comment on your message.

I re-read through the studies and yes, you are correct in that the pituitary expresses 5AR – thus use of Finasteride probably did inhibit 5AR/DHT activity in the brain.

Much like your theory about the pituitary no longer “seeing” low testosterone, I also speculated that perhaps we have undergone some form of pituitary desensitization due to downregulated and burnt out pituitary LHRH receptors thanks to Fin’s constant upregulation of Testosterone/LH – as discussed here (my 4th post down) propeciahelp.com/forum/viewtopic.php?t=258 . I’m not sure, but I thought I read somewhere that Tamoxifen and/or Clomid can resensitize the pituitary to Gonadotrophs (GnRH).

As for DHT treatment, haven’t heard of any concrete cases of recovery, although Dynaaminen mentions one guy from the old Yahoo forum in his post. It would appear DHT treatment is analogous to TRT, in that it will likely surpress T production and other hormones, as noted here:

jcem.endojournals.org/cgi/reprint/87/4/1467.pdf
“Serum concentrations of LH, FSH, E2, T, and SHBG decreased significantly during DHT treatment.”

According to the above statement, taking external DHT will surpress T production. Strangely enough, the above study parallels the experience for those of us who ended up with low T after quitting the drug – ie, perhaps our rebounding DHT to skyhigh levels, very quickly after stopping Finasteride could have signalled the pituitary to decrease LH, and thus T, since the Pituitary sensed a high level of DHT in the body and lowered T to compensate.

However, there are guys who have high DHT serum levels after Finasteride (albeit serum DHT is apparently not entirely accurate, one should measure its metabolite 3 -diol-G, aka 3a-androstanediol glucuronide via 24 urine panel, as well as androsterone/etiocholanolone (A/B) ratio in urine as a measure of 5a-reductase activity – see propeciahelp.com/forum/viewtopic.php?t=761)… and they still have issues.

Also, here is a former Finasteride users (Josh and John) who underwent DHT cream treatment under the care of Shippen, who did not have success:

groups.google.ca/group/alt.suppo … b2017722b1

Josh’s final story is here:
propeciahelp.com/forum/viewtopic.php?t=262

So I’m not sure if DHT treatment is the answer, but what do I know.

One thing is for sure, without doctors to discuss this with, like Dr. Shippen or others, we will never find out.

Look forward to your response, and hope you will post on the site.

Cheers,

Mew.


ANONYMOUS EMAIL #2:

Mew,

I continue to read the posts.

You have again posted another article dec 18 showing dht increases 5ar activity: propeciahelp.com/forum/viewtopic.php?p=4698

Also 1/3/08, Majkellos states Propecia destroys 5ar activity and you refer him to dynamin post – propeciahelp.com/forum/viewtopic.php?t=1079

I assume my input is not credible to you since you did not respond to my last email. I Assure i am a medical doctor. I read your last email to me.

Your logic is flawed in that you assume normal DHT in post-Fin users means 5AR is normal. They may be synthesizing dht from 5AR1 in skin and liver. My theory is 5ar2 gene expression is damaged. 5AR2 is in the brain and prostate.

Based on those studies I quoted in my first email, 5AR2 is in pituitary and prostate and that is where the damage is. The other study I quoted in my first email showed high doses of dht increased 5ar activity in the pituitary.

Also, you referred me to a man who took DHT ( propeciahelp.com/forum/viewtopic.php?t=262 ) and cited him as an example of DHT as a failure – BUT, if you read his post, he states DHT gave him excellent erections and he wished he could continue the DHT. Also, you cited DHT as a form of TRT – I never suggested DHT as TRT. The DHT is treatment to the damaged 5AR2.

You correctly cited DHT as TRT decreasing gonadotropins, so here is my solution:

  1. High DHT once a week to activate the 5AR2 in brain

  2. This will decrease testosterone in the pituitary and reverse the sensitivity of anterior pituitary to low testosterone, and restore 5AR2 activity in the prostate to increase NO (nitric oxide) synthesis and erectile function.

  3. Both DHT and NO will restore libido, as once a week DHT will not shut down gonadotropins.

  4. Remember, we are not trying to replace DHT – we are trying to restore 5AR2 activity. If it takes months, so what! Nobody is getting better with any other therapy so by now most are patient.

Again, note the dose of proviron that guy John used ( groups.google.ca/group/alt.suppo … b2017722b1 ) and time period, and was he cured? I suspect transdermal Testosterone once a week would also raise DHT pretty well.

Again none of the above is meant as medical advice… rather it is an idea to be presented to a medical doctor such as Dr. Shippen to review and refine it to be safe and effective under his care.


My (Mew’s) 2nd reply:

My friend,

Thank you for the reply. Your input IS credible to me, and I DID respond to your last email – hence you referencing the points I made in it (other guys trying DHT etc). Did you send an email after that? If so, I did not receive it.

You mention you are a medical doctor – from where, what country/hospital etc? What is your name/contact info? Do you have a profile on the web?

Funny that you should mention 5AR1 can make up for lack of 5AR2 via producing DHT – I actually came across a study that mentioned this was possible.

Thus, DHT values should not necessarily be taken at face values, since it may come from 5AR1. Yes, you are correct in that one guy’s story, he mentions the DHT shot helped him feel great, unsure why he would not continue.

I did however misinterpret your comments of a shourt course of DHT as a form of TRT… I understand your theory in more detail now, so thanks for explaining further.

Can I ask you a favor? Can you post the theories (both emails) you have sent me on the forum? Or would you prefer I do that and cite you as a user who has been privately messaging me this info?

I would love to present such theories to Dr Shippen, however I am not scheduled to see him. However, if your theory were on the forum, others who are going to see him might have a chance to get his feedback.

Thanks for the followup, let me know.

Mew


MY (Mew’s) 3rd email:

One last thing,

I went through the old Yahoo Group and found some posts by Dr. Crisler.

Here is what he said:


[i]Be forewarned–if you supplement DHT, then you reduce testosterone
production. Has to happen. I do not think that will help.

Regards,

Dr. John Crisler, DO[/i]


[i]Yes. The DHT is highly suppressive of the HPTA. Thus LH, and subsequently T (and E) levels will drop.

Regards,

Dr. John Crisler, DO[/i]


[i]"There are a couple of fundamental problems with these comments. When DHT is lowered, estrogens are elevated, de facto. Thus T levels go down, due to estrogenic inhibition at the HP.

There is no evidence that finasteride “destroys the 5-AR gene”, as the assays many of you have produced demonstrate healthy DHT levels status post Propecia cessation.

“Chronic high T elevation” does not cause liver toxicity—at least not at the levels we are dealing with here. In fact, the body is MUCHG healthier at the upper quartile of physiological range.

When Free T levels go down, LH production goes up, and this re-establishes baseline levels.[/i]

[i]Regards,

Dr. John Crisler, DO[/i]


ANONYMOUS EMAIL #3

Mew,

I would prefer not to post.You actually seem to be doing a great job finding the articles. Let me help you analyze the data. You can post my analysis as your own.

The key to my theory is propecia downregulates 5AR2 activity in the pituitary and genatalia leading to permanent hypogonadal hypogonadism.

This guy ( propeciahelp.com/forum/viewtopic.php?t=2261 )who used proviron is successfully treating himself by using TRT and HCG to maintain his testicular function. The proviron is DHT, which he uses to free up his testosterone, DHT and lower his E2. This should work, but it will not cure him because he is not upregulating the 5ar2 activity in his pituitary.

To do this properly one must NOT suppress the pituitary… this is the difficult part because this is uncharted territory.

All of this is based on the articles I already cited, to do this correctly one would have to do this under a physicians care. As you may have noticed I am not properly posting my cited articles and this is because i am a very busy physician and family man.

I propose you help me put together a proper letter with the proper articles referenced with footnotes and I will present the theory and general treatment to Dr. Shippen, and we will ask him to produce a treatment protocol, and hopefully he can start treating several patients and develop an efficacious treatment program.


ANONYMOUS EMAIL #4

Mew,

Have you come across any way to stop floaters with anti estrogens?


MY (Mew’s) 4th reply:

None that I know of. In fact, Clomid can induce floaters.

Regarding your previous msg and constructing a theory with footnotes, when I have some more time I will look into this.

You mention you are a physician, where are you located, what is your name, office address, phone number etc?

Cheers.


No further contact at this time.


#2

Hi Mew

Interesting stuff. When did this correspondence happen? What is your opinion of this theory?

Did you ever work on an approach to Shippen along these lines? (Just in case you don’t have enough to do, looking after this site.)

Strange that this guy won’t post on the site or tell us who he is.

Interesting, too, that an injection of DHT had that Josh guy feeling much better. Putting that together with JN’s story, I’m really starting to wonder if some form of DHT supplementation isn’t an answer (of a kind) for some guys. Not in any straightforward way because it supplies more DHT, but because it does something to make the body starting reacting normally to androgens again.

Check out JN’s story in detail. He had high T and high DHT, but T injections and oral DHT (Proviron) caused vast symptomatic improvement. Clearly he was not responding properly to his own androgen production. But when he added external DHT, something changed. It’s of note that it seems to have taken a good two months of Proviron before symptoms began to improve.

JN said that all this down to his high SHBG. He reckons that SHBG was binding to his DHT, rendering it useless. By taking Proviron, he says, he lowered SHBG, solving that problem.

I’m not so sure. We’ve seen guys with high SHBG who have brought down SHBG and not seen any improvement. I think something else was at work in his case, that’s to do with a change in androgen sensitivity.

I’m still not quite clear on whether supplementing with DHT necessarily lowers endogenous androgen production and supresses LH and FSH.

Anyway, it seems an avenue worth thinking about.

Contacting JN to see how he is now would be a huge help. I think Snowking is our best bet: he and JN were in close touch back when they emailed via the Yahoo forum. I’ve emailed Snowking via his website but if anyone has a more direct contact please do help.

By the way, Mew: are you goingt to try to contact Dynaaminen?


#3

excellent article. I think this guy is 100% dead on.


#4

Why do you keep asking him this? Are you trying to drive the guy away? He already stated that he has a very busy family, and professional life. Maybe he doesn’t want hundreds of depressed and desperate men trying to stalk him! Go figure!!
Plus, why is it even important!?
If the content of his theory sounds strong, which it seems like it does, just by judging your last few responses to him, why does his identity even matter, especially if he keeps offering to help!
Don’t drive him away man, just because you are looking for reasons to disbelieve his theory!

Why not respect his wishes, and try encouraging him instead! So maybe he continues to help!
What a thought huh!!


#5

Mew this is about the best theory I’ve read so far regarding a possible cure as it contains a lot of merit and logic. I’m willing to try this procedure through my endocronologist, can you please ask the good doctor the weekly dose of DHT he considers to be supraphsiologic and whether he has a preference for injections or transdermal. Also in a case like mine where high SHBG is an issue if it would have any bearing on the possible success of this procedure given it binds up a great deal of the DHT, thank-you for posting this.


#6

Correspondence happened around a year ago. However, I did not post it at the time as I figured he would, and I also had other things on the go, and forgot about it. Digging through old emails I came across our correspondence again.

My opinion on this theory is: there are many theories out there, but I don’t see why one could not try this under the care of a competent medical professional. All one needs is DHT treatment.

No I did not put together a letter yet, the correspondence above was the last of our emails. However I will work on getting this written up, basically taking his emails and putting footnotes, then getting in touch with him again.

Tried getting in touch with him a few times over the past 2 years, no answer. His last post on Yahoo Group was in 2006 so I assume he’s simply moved on with things.

For what purpose? From what I recall, Dynaaminen has other theories as to what caused his issues and no longer frequents this site.


As I have not been in contact since the emails, once the “theory” is properly written up, I will ask your question in my followup email to him.

As for injections or transdermal – if you read his initial email again, you will see he states the following:

"There is Intramuscular, transdermal and sublingual – sublingual seems to drop off quick, so there’s little effect on the HPTA but it can create a significant plasma rise and possible stimulate prostate and pituitary 5AR mRNA repair. "

So I think therein lies your answer. Second to that you may want to consider intramuscular based on Josh’s (Dave Fulmore) post in the emails, where Josh states Shippen gave him a DHT injection and it was the best he had felt in 2 years.

That I do not know… you may want to look into lowering your SHBG beforehand, I believe Shippen uses low-dose Danazol for this but do your research.


#7

There’s a couple things I guess I’m trying to keep in mind perhaps you could shed more light on them mew. Firstly, is the doctor basically saying that the guy using proviron wasn’t curing the problem due to the fact that the drug doesn’t affect the hpta or the dose isnt high enough? Furthermore, if this can be translated into increasing DHT/5ar through psycological means such as dopamine and gaba it would make sense that a direct shot of the hormone might be the best way to combat the problem. A couple things to keep in mind if this theory holds true though is that the guys who have fully 100% recovered increased their DHT naturally through supplements etc thus increasing 5AR. If one was to try this using a synthetic method ie a shot especially at a relatively high dose the body might have a different reaction and it could cause down regulation of testosterone etc. Furthermore, as someone who works in the insurance industry, and knows the trouble with lawsuits that MDs face these days it would be hard pressed to find a doctor who would be willing to experiment with this. The best bet would be shippen who seems like the only one who would really go out on the line and experiment to solve the problem.

It would be wonderful if someone was willing to be a guinea pig and try this out. I myself have thought about going to shippen and presenting him with the info in person, he seems like a reasonable guy who has been more than willing to work with us over the years. Oh and an interesting note on this theory. Mew posted the study awhile back which can be seen in the Paul Walters thread about how GHB increased GABA and allopregnelone production thus resulting in probably an increase in DHT/5AR. I know that when i take it the following day im a bit hung over feeling etc but the next night, without taking ghb, i sleep like a baby and wake up feeling the best ive felt since this all started. this all would possibly hold true that ghb does in fact possibly increase DHT/5AR. Also look at the old posts by Josh and Jake, one had success for his sexual sides from using a shot of DHT while the other didnt have much success sexually but said he was sleeping and feeling a lot better through the use of cream. I dunno I’m following my gut here but I really feel like this could be the answer to our issues. After reading all the studies on here and all the theories over the past couple years this just makes the most logic sense.


#8

I’m just about to start a course of Tamox. If that doesn’t work out, I’d be glad to be a guinea pig for this theory. I’m working with a pretty open minded endo, there is a tiny chance he’d give it a shot.

I’ll come back to you guys in a couple of months. Won’t be around much till I have something to report.

In the meantime, maybe someone currently under the care of Shippen or Crisler should put this idea forward?

It has to be said, though, that all this is speculation. Guys such as Awor have tried supplementing with large doses of DHT and seen no improvement.

It also strikes me as strange that a doctor would ask a layman (Mew) to write up his ideas (with footnotes, no less) so that he can present them to another doctor (Shippen). I’m not sure that Mew needs to go to all the effort of putting a formal proposal together. It doesn’t seem as though this doctor is too desperate to remain involved, seeing as he has not been in touch for a year. So it would be enough, surely, for the next guy who goes to see Shippen or Crisler to simply discuss the theory, which is simple: a short course of high-dose DHT in the hope of promoting 5AR activity. We don’t need to cover Shippen or Crisler in footnotes in order to suggest this. It will probably be clear to them pretty quickly whether the idea makes any medical sense.

Hey Mew: I was only thinking about Dynaaminen because the story of JN’s recovery reminded me that Dyna posted a recovery too, back in Oct 2008. It’s called “Finally a period of recovery!”

I can’t see anything in his posts that suggest he put his issues down to anything other than finasteride; did I miss something?

As you know (but newer members might not) his is a pretty significant recovery: he experienced all the major sides for years. I’d be intrigued to know how he’s doing now. I’ve send him a pm; have to see if he comes back. Anyway, like JN’s recovery, his story should encourage all of us.


#9

Which supplements are these?

Do you have any studies showing GHB increases 5AR2 and DHT? Otherwise this is simply pure speculation… no offense.


#10

I read a lot of what goes on in the forum, I don’t post much because I have been in a process of grasping this problem more so than in a position to make a genuine contribution from a serious understanding of the entire problem.

I would like to say that lately I have enjoyed the whole androgen insensitivity and downregulation line of thinking that has been discussed, it makes A LOT of sense to me. Moreover, I think the elephant in the room for many of us who are ascribing to this theory has been how to upregulate once again.

With this in mind, I would like to thank MEW for remembering this e-mail and posting it in here. I know that this is not guaranteed to be any kind of a solution, however it speaks very poignantly to this downregulation theory and becomes a very serious next step to be explored, inasmuch as this theory is concerned.

MEW, your analytical thinking and intuition in addressing this problem are incredible in my book. I am not saying this with intent to offend any of the other contributors, and certainly there have been plenty of other valid contributors, but I think most of us should be appreciative of MEW and his dedication to this problem, along with the man hours he has put into it.

Keep it up, I am sure we will find a way out of the woods yet, as long as we have good people that are willing to give this their best and collaborate with others and with doctors.

Sorry if this post seemed a little gay. I mean gay in the “non-sexual derisive meaning, equivalent to rubbish or stupid (as in “That’s so gay.”)”


#11

I wrote my doctor and included the threads about androgen insensitivity and this one as well. Just trying to get an additional medical opinion on the validity of these arguments / thought processes. When she gets back to me I will post.


#12

Just some question about this theory…I think this theory makes a lot of logic and it could be a good theory but… about the experience of ithappens by using GHB ,he said he turned his sexual function “180” just using GHB 10 days.
I used GHB for 10 days and I had some times having strong and real erections during the night (not libido) so … the theory above could be right based on the long term .
I’m asking my self how can GHB let the erections come just in 1-2 weeks?..ithappens is the proof. if it was just due to the dht the body has to produce,I think it ll take a long time to produce it,but having erections just in 1-2weeks maybe it’s because of the neuro connections that GHB can restore …

for sure I think we have a lack of dht/androgens but another experience I had 2 times, is that I cryed so strong cause of the best girl I ve ever loved and she brake down with me 2 times in theese last 3 mouths,so 2 days ago I was cryeing …the real crying when u’re in love and you are desperated,so yesterday night I felt my penis more connected and could have a strong erection with more controll of my stuff down there…so this let me think that it’s something about my brain and connection that is fucked up…I don’t know if GHB can let the body produce more DHT in just 2 weeks…(maybe it’s like that,cause normal ppl recover from stopping propecia in just 2 weeks or so)…

…I’m just thinking …


#13

Italy,

I agree with you in the fact that I think it is a neurological issue as well. The reason I think this is because of my own experiences. When my head feels clear and is firing on all neurons, I can feel my erection “in my head” so to speak. When everything is working as it should, my erections are fatter, more sensitive and more connected. After all, sex starts in the brain and no where else. When I feel horny, this comes from my head, then goes down to my cock. My brain tells my cock, okay, fill up and fill up good. On the other side of the coin, when my head is in the shitter, everything else follows. My erections suck, I"m not horny, I have no sensitivity, you know the deal. I think what they are purposing with this theory is that the DHT in the brain, or lack thereof, is what is causing the problems. If that’s the case, I think it makes sense and follows what we are vocalizing here.


#14

I understand you,it s exactly the same for me… next weekk i ll be to Paolo Peccoz and will ask him about androgens insensibility test and what does he think about ths theory…thanks


#15

sigh does no one listen to me around here.

Italy. You had what I had, an “emotional catharsis”. If you have had emotional blunting, and you really forced yourself to feel again, you probably stimulated dopamine. Dopamine is the pleasure chemical, and like I have said, I believe it gives the pleasurable connection between the penile nerves and the brain. The more emotions you feel, the more dopamine is working, the more you are recovering. You think you can fuck without dopamine? I doubt so.

Moreover, we all lack dopamine if we have brain fog. A hell of a lot of dopamine is made where? Adrenal glands. Back there again.

I really don’t know why people are talking about DHT production when there are bigger fish to fry. Most people have their balls “offline” anyway, producing minimal androgen due to lack of deep sleep (IMO), so… yeah. DHT is important but I don’t see it saving you.


#16

Can you provide scientific resources to substantiate this claim?

I was under the impression dopamine is produced primarely in the brain, ie:
en.wikipedia.org/wiki/Dopamine

EDIT: found some corroboration of your statement – books.google.ca/books?id=x2CD5Wk … t#PPA91,M1


#17

Right… I’m not saying the majority of dopamine is produced by the adrenal glands (I have not come across proportions), I’m just saying that it is a recognized source of this neurochemical. I believe it is enough of a substantial source to cause the absence of necessary dopamine in our bodies/brains and leave us with cognitive dysfunctions and brain fog.

The only real question I am coming up against currently is… Is it a matter of the well-known adrenal insufficiency, or is the pituitary ACTH just insufficient? As we know I have been suspect of the relevance GABA has to the anterior pituitary secretion and function ever since the success and reversals of symptoms we have all seen using GABA analogues. I suppose only significant testing can truly answer this question.


#18

I’ll try to find some studies on this, but as far as I know, dopamine is made in the adrenals, but does not cross the blood brain barrier (this is why L-dopa and not dopamine is used to treat parkinsonian type symptoms).

Also, 5AR inhibition, as we know affects allopregnanolone synthesis which positively modulates GABA activity. The interplay between glutamate and GABA is very important in normal behavior. When GABA receptors are relatively under-activated, there is less of a brake on the excitatory pathways, most of which release glutamate.

Finally, glutamate levels can modulate dopamine levels. I’m not sure which way, but I think the dynamic is brain region- and receptor type- specific. Again, I’ll try to find some related studies on pubmed.


#19

I understand that there are many theories on what exactly our problem is… Is it cortisol? Is it GABA? Or maybe Androgen Resistance, Serotonin or Dopamine? These and all the others that have been explored in this forum are all based in realities and have very strong arguments supporting them.

My very simplified logic always leads me to the following conclusion, though. What do we all have in common? We all took a pill that inhibited 5AR2 and consequently DHT. DHT regulates its own gene expression. So while we have appropriate theoretical amounts in our genetic code, we are no longer expressing that part of our genetic code.

I feel like all the other things GABA, Cortisol, etc. developed as a result or “Downstream” effect of this initial primary problem. Moreover, this is where each person’s particular experience might vary considerably, depending on our own unique chemistry. Let’s assume that GABA is in fact responsible for 2 very specific side effects (lets just say anxiety, and fatigue). We can attempt to treat a problem with GABA regulation, however, if we don’t fix the root problem prior to doing so it is unlikely to work as well, or it may recur, as we continue to lack the DHT we are meant to have.

I know for a fact my DHT is not normalized, and I don’t need a blood test to tell me. My hair is still not falling out, my skin is not yet oily like it once was (8 months off). These are external signs that my body tells me it is not producing, absorbing, or utilizing this one specific hormone like it always did. If I do not get this normalized I will not be able to fix all the problems that it caused in the first place. My very optimistic idea is that many of these things will sort themselves out once we normalize DHT, but if not, the time to treat them is AFTER we fix the root cause, not before. This is just my humble opinion.

The theory that most worries me is the one that falls outside this “umbrella” of DHT’s genetic expression, and that is “Androgen Resistance”. It seems to me the most difficult to treat.


#20

I’m lucky or blessed enough to have a buddy of mine, (used to be best friends with him till he moved away from me when i was 15 but now is back in the area) who competes in body building competitions and knows about how to aquire many anabolics. I got in touch with him recently inquiring about masteron. For those of you that don’t know Masteron is an anabolic that mainly works by raising DHT levels. Body Builders will take it before a competition because, while it doesn’t serve much purpose in terms of increasing muscle mass like TRT, it instead cuts down on body fat to give the muscles a more ripped look. It’s also a potent anti-estrogen, and there’s a study that i can’t find, but it’s actually been experimented and found effective in the treatment of breast cancer cells. My friend basically told me it’s great stuff just very expensive, but it would no problem getting it for me. As of now I’m still researching and looking into it, but I may take it upon myself to try it. I would have a lot of apprehension doing it without a doctor’s supervision, but at the same time I gave up on waiting on doctors to come around long ago. Either way we’ll see.