DHT and Testosterone kills hair DIRECTLY........study

[S Foote.]

I posted that study simply because it shows what a mixed bag of pointless, scientificaly meaningless results follicle "in-vitro" studies produce.

Thats the lesson here! :wink:

Stephen, the really funny thing about you is that you are so bereft of any scientific evidence at all in support of your theory, you're reduced to searching through the available studies and hoping to find an occasional inconsistency or disagreement on some technical issue or experimental finding. Then when you do find something like that, you proudly trumpet it to anyone who will listen: "Look! Look! See, I told you so!! There are HUGE problems with the accepted theory of balding!!!" You just crack me up, Stephen!

Bryan

That's really funny Bryan "YOU" trying to acuse me of cherry picking :roll:

This comes from the person who claimed a fifty year old transplantation study "proved" beyond question your personal beliefs.

http://www.hairlosstalk.com/discussions ... hp?t=17571

Then you showed your total ignorance of the now recognised common long term balding in the very same grafts, and modern evidence in transplantation in gereral :roll:

Next we had you (quite rightly for once), posting that mouse study and questioning the traditional idea's on the androgen "direct" effect.

http://www.hairlosshelp.com/forums/mess ... &forumid=1

But then as soon as you realised (slowly as usual), that this study supported "my" ideas, you tried to desperately play this down :roll:

Thats a "VERY" scientific attitude Bryan (NOT) :wink:

Now answer my question?

You said you had something to say about the non response i got from ICX, so tell us Bryan?

S Foote.

 

[CCS]

Bryan, do you think green tea extract is nearly as strong as RU58841 at blocking the androgen receptor? And in the study Old Baldy reposted that you posted back in 2001, do you know what vehicle was used to give the hampster flank organ 1mg? Thanks.

 

[arya]

Man! More I read, more i get confused :cry:

 

[docj077]

I'm not sure what all this craziness is about, but I figured that maybe I could add a few new thoughts.

Testosterone and Dihydrotestosterone can both bind to androgen receptors. DHT has a higher affinity, but that doesn't mean that it causes a different signaling pathway to occur. They both will cause the release of transforming growth factor-beta in the scalp, which will inhibit the proliferation of any cell it touches. That's the basic science.

The problem with drugs like Propecia and Avodart is that they do indeed increase Testosterone levels for relatively short periods of time, because they inhibit the creation of DHT in the scalp (propecia and avodart) and the skin (avodart).

These treatments only work in certain individuals as the degree of male pattern baldness is related to the number of repeats present in the gene that codes for your androgen receptor. I do not remember the specifics, but I believe that the greater the number of repeats you have the worse your male pattern baldness will be, but the better you will respond to treatment. The opposite is also true.

These drugs cause many problems and should not be taken lightly. 5alpha reductase is in numerous tissues and the periodic shift in testosterone levels can directly inhibit the release of gonadotropins from the anterior pituitary causing decreased spermatogenesis and in susceptible individuals, the symptoms of low testosterone.

This isn't the only problem. If, like me, you've recently developed hyperthyroidism while on Propecia, you'll see that it's due to a back up metabolites in the sex hormone pathway all the way back to progesterone. The enzymes in your body can not take progesterone all the way to testosterone if too much testosterone is already in your system. That's just simple enzyme kinetics with too much product preventing the enzymatic conversion of substrate as the enzyme approaches Vmax. Progesterone directly increases activity in the thyroid gland. So, I've developed drug-induced hyperthyroidism as a result of taking propecia. How do I know, because every scan or imaging technique that is known to man has come back normal and yet my free T4 is constantly elevated. I've lost weight, muscle mass, developed tremors, headaches, and palpitations. Not only that, but my prostate has been kind enough to grant me prostatitis privileges.

Anyway, enough about my life. I just wanted to share this. The good news is that progesterone has been found to have a neuroprotective effect according to studies I've read. Is this true in males? I have no idea, but I sure don't feel smarter most of the time.

Is this scenario a possible truism for everyone? No, but it should be considered. You body has the conversion of testosterone to DHT as a metabolic process for a reason.

Just so everyone knows, I'm still on proscar, but I'm slowly wheening myself off it.

 

[powersam]

as far as i know docj077, the increase of scalp testosterone is permanent for the time you are on finasteride or dutasteride, not temporary.

 

[docj077]

as far as i know docj077, the increase of scalp testosterone is permanent for the time you are on finasteride or dutasteride, not temporary.

Really? I expected it to end up being bound to a binding protein and shipped away for conversion to estrogen. But, I suppose it could hang around for a while.

I would think that the testosterone concentration in the scalp would fluctuate as the testosterone levels in the body fluctuate. But, as the studies have shown everyone, the scalp environment is a rather strange place.

 

[Bryan]

as far as i know docj077, the increase of scalp testosterone is permanent for the time you are on finasteride or dutasteride, not temporary.

Really? I expected it to end up being bound to a binding protein and shipped away for conversion to estrogen. But, I suppose it could hang around for a while.

I would think that the testosterone concentration in the scalp would fluctuate as the testosterone levels in the body fluctuate. But, as the studies have shown everyone, the scalp environment is a rather strange place.

I don't understand where you're coming from, in both this and your previous post. Testosterone will continue to be upregulated a bit for as long as you continue to take finasteride or dutasteride, so I don't know where you got the idea that testosterone will be increased "for relatively short periods of time". That doesn't make any sense. Are you also under the impression that those drugs only reduce DHT "for relatively short periods of time"?

Bryan

 

[CCS]

Testosterone and Dihydrotestosterone can both bind to androgen receptors. DHT has a higher affinity, but that doesn't mean that it causes a different signaling pathway to occur. They both will cause the release of transforming growth factor-beta in the scalp, which will inhibit the proliferation of any cell it touches. That's the basic science.

Don't lots of things bind to androgen receptors? Does estrogen? We know spironolactone and RU don't make it do that. What makes you so sure that every molecule that binds to it, except anti-androgens, give it the same command? Or so sure that testosterone and DHT give it the same command? Have there been tests done to prove this?

 

[Ams99]

that little article didn't directly say high t levels alone can cause any damage, it was also inclusive of high dht levels as well. this doesn't offer a reason to believe that a drug like avodart which will raise t levels but dramatically decrease dht will increase hairloss due to the small spike in t-levels.

 

[docj077]

as far as i know docj077, the increase of scalp testosterone is permanent for the time you are on finasteride or dutasteride, not temporary.

Really? I expected it to end up being bound to a binding protein and shipped away for conversion to estrogen. But, I suppose it could hang around for a while.

I would think that the testosterone concentration in the scalp would fluctuate as the testosterone levels in the body fluctuate. But, as the studies have shown everyone, the scalp environment is a rather strange place.

I don't understand where you're coming from, in both this and your previous post. Testosterone will continue to be upregulated a bit for as long as you continue to take finasteride or dutasteride, so I don't know where you got the idea that testosterone will be increased "for relatively short periods of time". That doesn't make any sense. Are you also under the impression that those drugs only reduce DHT "for relatively short periods of time"?

Bryan

Testosterone can not be continually upregulated according to human physiology. Any testosterone level that strays above the set points provided by the body inhibits both the anterior pituitary and the hypothalamus. Testosterone inhibits the release of both gonadotropins and GnRH.

This is taken from the Journal of Endocrinology. If you need a better reference, let me know.

There are two pathways that testosterone can take once you take a 5AR inhibitor. It can either inhibit it's own synthesis by decreasing it's upstream releasing factors for an extended period of time, which will eventually cause decreased overall testosterone or it can inhibit it's own synthesis during the time periods that GnRH would be secreted which is well timed and not constant. Thus, you either end up with a permanent decrease in testosterone, fluctuating testosterone levels, or a normalizing of testosterone, which will increase all upstream metabolites such as progesterone and the testosterone will use CYP19 aromatase to convert to Estrogen. All this depends on the physiology the specific individual in question.

 

[docj077]

Testosterone and Dihydrotestosterone can both bind to androgen receptors. DHT has a higher affinity, but that doesn't mean that it causes a different signaling pathway to occur. They both will cause the release of transforming growth factor-beta in the scalp, which will inhibit the proliferation of any cell it touches. That's the basic science.

Don't lots of things bind to androgen receptors? Does estrogen? We know spironolactone and RU don't make it do that. What makes you so sure that every molecule that binds to it, except anti-androgens, give it the same command? Or so sure that testosterone and DHT give it the same command? Have there been tests done to prove this?

It's called an androgen receptor for a reason. Estrogen isn't an androgen. Only androgens activate the receptor and both testosterone and DHT have the same downstream effects in scalp hair follicles, which is to release TGF-beta. It's just that DHT has a higher affinity, so it causes a better downstream response. Anti-androgens can either bind the androgen or bind the receptor. They do not activate the receptor when bound due to their chemical nature. I believe they bind covalently and permanently deactivate the receptor, but I'm not sure. This isn't a permanent cure, because those cells can constantly make new receptors.

When you bind a receptor there are two responses. Activate or deactivate. All androgens activate the androgen receptors.

When testosterone binds to the androgen receptor, it is far less stable than when DHT binds to the receptor. Since the complex is less stable it is unable to transform to the DNA binding state efficiently. The DHT-receptor complex does not have this problem, which means that it's better able to bind to DNA and initiate the transcription of the genes responsible for the proteins that create the downstream effects that cause hair loss.

It's the previously mentioned complex and its binding state that allows for different genes to be transcribed in the complexes presence. That's the reason why testosterone causes virilization of the wolffian ducts (internal genitalia) and DHT causes external virilization and the development of secondary sexual characteristics even though they bind the same receptor.

 

[Bryan]

I don't understand where you're coming from, in both this and your previous post. Testosterone will continue to be upregulated a bit for as long as you continue to take finasteride or dutasteride, so I don't know where you got the idea that testosterone will be increased "for relatively short periods of time". That doesn't make any sense. Are you also under the impression that those drugs only reduce DHT "for relatively short periods of time"?

Testosterone can not be continually upregulated according to human physiology. Any testosterone level that strays above the set points provided by the body inhibits both the anterior pituitary and the hypothalamus. Testosterone inhibits the release of both gonadotropins and GnRH.

You didn't understand my explanation. When I told you that testosterone will continue to be upregulated as long as you continue to take finasteride or dutasteride, I meant that the set point will be elevated during the entire time that you're taking either of those drugs. Now that you know what I mean, go back and re-read my paragraph above.

Bryan

 

[michael barry]

DocJo77


Ive taken finasteride for a decade now. I havent had sides, but since you do.....................................I tested revivogen on a wrist a while back to see if it was a potent anti-androgen. Crinagen was tested on the other wrist. In less than three months, the revivogen wrist hair was severely stunted, weakly pigmented and very thin (Im a pretty hairy guy). I was on finasteride at this time. I honestly think the extra kick from it comes from the inbition of type 1 alpha five reductase as well as type two, BUT especially the beta sitosterol content. I really think it compedively binds with receptor sites and is read as an estrogen or pehaps binds with the androgen hormones floating around. There is no other reason it worked so well on my wrist. Cringan did practically nothing.



So, if youre looking for an anti-androgen.......................I'd eagerly suggest you buy one bottle of it and put it on your forearm or a similar spot with good body hair every day for about 3-4 months and test it on yourself. If you get a good result......................you might have a good anti-androgenic topical. I was impressed with it.

 

[docj077]

DocJo77


Ive taken finasteride for a decade now. I havent had sides, but since you do.....................................I tested revivogen on a wrist a while back to see if it was a potent anti-androgen. Crinagen was tested on the other wrist. In less than three months, the revivogen wrist hair was severely stunted, weakly pigmented and very thin (Im a pretty hairy guy). I was on finasteride at this time. I honestly think the extra kick from it comes from the inbition of type 1 alpha five reductase as well as type two, BUT especially the beta sitosterol content. I really think it compedively binds with receptor sites and is read as an estrogen or pehaps binds with the androgen hormones floating around. There is no other reason it worked so well on my wrist. Cringan did practically nothing.



So, if youre looking for an anti-androgen.......................I'd eagerly suggest you buy one bottle of it and put it on your forearm or a similar spot with good body hair every day for about 3-4 months and test it on yourself. If you get a good result......................you might have a good anti-androgenic topical. I was impressed with it.

Well, I've tried Revivogen before and it was pretty ineffective. I'm going to lower my propecia to 0.5 mg per day to hopefully decrease my serum and scalp DHT levels while also decreasing the side effects. However, I do not plan on staying on this drug indefinitely. Personally, I'm going to wait for a TGF-beta inhibitor. That's the real answer, in my opinion, as it targets something other than a receptor that can bind multiple molecules. Unfortunately, taking such a drug internally will cause cancer and I'm pretty sure that any person who has sun burned their head will also have problems.

Also, for anyone who is curious I just read that 5 alpha reductase inhibitors also inhibit the metabolism of progesterone as 5 alpha reductase has been shown to bind and metabolize that particular molecule. Apparently it's a recent study, but it would also explain my hyperthyroidism.

 

[docj077]

I don't understand where you're coming from, in both this and your previous post. Testosterone will continue to be upregulated a bit for as long as you continue to take finasteride or dutasteride, so I don't know where you got the idea that testosterone will be increased "for relatively short periods of time". That doesn't make any sense. Are you also under the impression that those drugs only reduce DHT "for relatively short periods of time"?

Testosterone can not be continually upregulated according to human physiology. Any testosterone level that strays above the set points provided by the body inhibits both the anterior pituitary and the hypothalamus. Testosterone inhibits the release of both gonadotropins and GnRH.

You didn't understand my explanation. When I told you that testosterone will continue to be upregulated as long as you continue to take finasteride or dutasteride, I meant that the set point will be elevated during the entire time that you're taking either of those drugs. Now that you know what I mean, go back and re-read my paragraph above.

Bryan

I understood your explanation. You just didn't specify the physiological mechanism of the testosterone increase and that's why you confused me.

No worries, however. I do agree that changing the set point will allow for incredible testosterone increases. However, these increases will also allow for the estrogen increases that are seen in Finasteride users.

So, that's probably the problem. Those that can increase their set point without any difficulty get gynocomastia due to the estrogens. Those that can't end up with the symptoms of low testosterone due to any increased production inhibiting the anterior pituitary and hypothalamus.

I think we've pretty much solved the reasons for the diversity in the symptoms that people seem to see.

 

[CCS]

what are the early warning signs of thyroid problems? I'm fitter and more muscular than ever.

 

[docj077]

what are the early warning signs of thyroid problems? I'm fitter and more muscular than ever.

Well, my I have a family history of hyperthyroidism on my mom's side of the family.

The early warning signs are weight loss, hyperphagia (extreme hunger), palpitations, sweating, fatigue and tremors.

When I first started propecia I also put on a lot of muscle, but I suddenly started loosing weight and and felt fatigued constantly. After that, I started having little thyroid attacks that caused me to sweat, have tremors, and mild palpitations.

 

[Bryan]

I understood your explanation. You just didn't specify the physiological mechanism of the testosterone increase and that's why you confused me.

I'm still not sure you understand what I'm saying. Tell me in a little more detail what you think my explanation is for the increase in testosterone with finasteride usage.

No worries, however. I do agree that changing the set point will allow for incredible testosterone increases.

"Incredible" testosterone increases?? I really don't think we're on the same page. Testosterone only increases by about 10% or so at the most, when you take finasteride.

So, that's probably the problem. Those that can increase their set point without any difficulty get gynocomastia due to the estrogens. Those that can't end up with the symptoms of low testosterone due to any increased production inhibiting the anterior pituitary and hypothalamus.

That's yet another statement that makes me think we're not on the same page! Do what I suggested above, and let's see if we can get this misunderstanding cleared up...

Bryan

 

[docj077]

Bryan,

Any increase in testosterone is enough to negatively regulate GnRH, LH, and FSH secretion. Even 10%.

I really don't know why you're struggling with what I'm saying. I understand you perfectly. You seem to be saying that the drugs Propecia and Avodart allow for or at least encourage a change in the set point of an individual to allow for that small 10% or whatever increase in testosterone levels. I agree with you. Granted, I must be using some sort of foreign hyperbole to describe my view of the subject, but that's what I'm seeing.

In my mind, if a male can not adequately regulate their testosterone set point, they will end up with excess estrogens above normal limits, which will allow for the slow development of gynocomastia. Also, to me, if a male can regulate their set point, then they shouldn't have any problems. However, if a male takes too long to reset their set point, then they will have the symptoms of decreased testosterone as during that time period before the set point shift, they will have slightly increased testosterone, whcih will eventually cause decreased testosterone due to feedback mechanism.

Granted, the last part is my opinion, but I'm pretty sure I get what you're saying. Do you get what I'm saying?

 

[Bryan]

Now I know for sure that you didn't understand what I was saying all that time!

I'm going to explain it to you in more detail, and hopefully this will clear it up once and for all: DHT is also a player (along with testosterone and estrogen) in the hypothalamic-pituitary-gonadal axis that controls the production of testosterone. When you take finasteride or dutasteride, your levels of DHT sharply drop, which the brain interprets as a sign of decreased androgenic stimulation. Its response to that is to step-up the production of testosterone, to compensate. It does that by sending the chemical signals LH and FSH to the testes to tell them to start working overtime.

THAT is why testosterone increases when you take finasteride: the brain tells the testes to make more of it. It's not the simplistic notion that less T is turned into DHT, so there's more T floating around. In other words, the body's set point for testosterone (that is, the level of testosterone that the brain WANTS to have) is actually increased, and it's MAINTAINED at that new, higher level, for as long as you take the finasteride. Now do you understand what I'm saying?

Bryan