compiling a list of theories for Male Pattern Baldness

1) calcification of the skull/ diploic veins . the  Dr. Ballenger theory
2) simply being malnourished / vitamin / mineral deficiency.
3) too much dht in the follicle / stress which causes DHT
4) a problem with energy metabolism
5) a thyroid problem
edit 6) viewing hair loss as heart disease and solving it that way

Any more you can add ?

number 5, 4 and 1 may be connected

iuyyighghghgkh wrote:1) calcification of the skull/ diploic veins . the  Dr. Ballenger theory
2) simply being malnourished / vitamin / mineral deficiency.
3) too much dht in the follicle / stress which causes DHT
4) a problem with energy metabolism
5) a thyroid problem

Any more you can add ?

number 5, 4 and 1 may be connected

all of them are connected.

There are theories of other causes being responsible for MPB:
- skull expansion
- neurosis
- thermoregulation problems
- etc...

Beebrox wrote:

iuyyighghghgkh wrote:1) calcification of the skull/ diploic veins . the  Dr. Ballenger theory
2) simply being malnourished / vitamin / mineral deficiency.
3) too much dht in the follicle / stress which causes DHT
4) a problem with energy metabolism
5) a thyroid problem

Any more you can add ?

number 5, 4 and 1 may be connected

all of them are connected.

There are theories of other causes being responsible for MPB:
- skull expansion
- neurosis
- thermoregulation problems
- etc...

thermoregulation problems = thyroid problem
skull expansion = the calcification theory

true. I believe in total redundancy in the body. Every indicator is also a control for something else.

I do personally feel all of them are connected, and the fact that we've given ourselves the task of assembling all of these theories only points out the fact our knowledge of the whole system is fragmented.

But there is a theory I do like and I'll toss into the mix:

The susceptibility of the hair follicles in the scalp is fundamentally genetic. Variability in trinucleotide repeats on the X-chromosome increase the sensitivity of steroid receptors in the scalp follicles to DHT. Basically your scalp hair has more sensitive antennae to your androgen levels. The argument is that this sensitivity evolved as a response to increased free androgen levels, because these correlate heavily with prostate pathologies such as cancer. Hair which would thin and/or fall from the scalp increased the surface area exposed to sunlight, increasing the individual's vitamin D status, augmenting systemmic immunity and increasing the likelihood of survival (or prevention) of prostate disease. The hair responding directly to the agent which promotes hyperlasia of the prostate supports this theory. The fact that prostate cancers were only an evolutionary pressure on men also supports this theory and why pattern hair loss is a male malady (mostly), and why the genetic programming would make you more sensitive to a predominantly male hormone, and also why these genetic variations would be borne by the X-chromosome. A woman receiving two doses of the X-chromosome would likely receive some type of protection from this sensitivity of the follicles, somehow related to her double dose of the X genes. While a man, receiving only 1 X-chromosome helps to explain the mostly male presentation of the susceptibility. But this would also support how some, but much fewer, women would statistically experience pattern hair loss as well. Although this wouldn't present them with the same increased survival advantage.

This theory does a better job of tying some of the disparate observations about MPB together, compared to a lot of the theories I've come across. The genetic component. The distribution between males and females. The auto-immune component. The perpetuation of the condition across many generations, and its widespread nature. Why a higher ratio of estrogens:testosterone seems to be protective of the hair.

Although the obvious downside of ascribing yourself to this theory is that there isn't jack shit you can do about it until a more targeted and specific form of therapy comes down the pipe, well besides attempting to modulate your own immune response with anti-inflammatory therapies. There's no doubt our lifestyles, diets, sleep, etc. do augment our own immunity and can make this occur more rapidly. So I think we can have an impact, albeit not as total as we'd like it to be.

102 wrote:
The susceptibility of the hair follicles in the scalp is fundamentally genetic.

Hair loss isn't genetic I think. Look at people who adopt western diets who have no history of hair loss, and bang, they do now.

102 wrote:
Variability in trinucleotide repeats on the X-chromosome increase the sensitivity of steroid receptors in the scalp follicles to DHT. Basically your scalp hair has more sensitive antennae to your androgen levels. The argument is that this sensitivity evolved as a response to increased free androgen levels, because these correlate heavily with prostate pathologies such as cancer. Hair which would thin and/or fall from the scalp increased the surface area exposed to sunlight, increasing the individual's vitamin D status, augmenting systemmic immunity and increasing the likelihood of survival (or prevention) of prostate disease. The hair responding directly to the agent which promotes hyperlasia of the prostate supports this theory. The fact that prostate cancers were only an evolutionary pressure on men also supports this theory and why pattern hair loss is a male malady (mostly), and why the genetic programming would make you more sensitive to a predominantly male hormone, and also why these genetic variations would be borne by the X-chromosome. A woman receiving two doses of the X-chromosome would likely receive some type of protection from this sensitivity of the follicles, somehow related to her double dose of the X genes. While a man, receiving only 1 X-chromosome helps to explain the mostly male presentation of the susceptibility. But this would also support how some, but much fewer, women would statistically experience pattern hair loss as well. Although this wouldn't present them with the same increased survival advantage.

102 wrote:
This theory does a better job of tying some of the disparate observations about MPB together, compared to a lot of the theories I've come across. The genetic component. The distribution between males and females. The auto-immune component. The perpetuation of the condition across many generations, and its widespread nature. Why a higher ratio of estrogens:testosterone seems to be protective of the hair.

Although the obvious downside of ascribing yourself to this theory is that there isn't jack shit you can do about it until a more targeted and specific form of therapy comes down the pipe, well besides attempting to modulate your own immune response with anti-inflammatory therapies. There's no doubt our lifestyles, diets, sleep, etc. do augment our own immunity and can make this occur more rapidly. So I think we can have an impact, albeit not as total as we'd like it to be.

You could reasonably argue that genetics isn't deterministic, and I'd agree there are many epigenetic factors that could contribute and augment the underlying process. But I'd respectfully disagree that there isn't a genetic core cause of this problem. Its just flying in the face of what modern science recognizes about human physiology, and what research has shown specifically with regard to male pattern baldness. Any theory which we're going to take seriously has to include a genetic component.

102 wrote:You could reasonably argue that genetics isn't deterministic, and I'd agree there are many epigenetic factors that could contribute and augment the underlying process. But I'd respectfully disagree that there isn't a genetic core cause of this problem. Its just flying in the face of what modern science recognizes about human physiology, and what research has shown specifically with regard to male pattern baldness. Any theory which we're going to take seriously has to include a genetic component.

Yes but the genetic component of all of this, is how much a follicle is responsive and sensitive to certain things. And that enviroment can be manipulated. And everyone has this component. Take a guy with a full head of hair. Strap something around his scalp in a way that it will restrain all the blood flow creating severe chronic hypoxia. Put him on a inflammatory diet eating nothing but gluten and candy. Have him masturbate 5 times a day every day. That guy will most likely thin and lose about half his hair in a matter of 6 months. Pure speculation time wise though.

Genetic component is the obvious, and hard to disagree about the sensitivity part. But sensitive to what? DHT alone? I doubt it greatly.

However epigenetic is what is the (hard tasked) goal here, regardless of disposition.  I disagree that it can not be done. However it can/might marry and tax the balder with the everyday dedication in order to keep things in check, until the breakthrough is made via new type of healing/put more dots into the equation. I think also technology can make it a whole lot easier for us. So where is the fun of it? In knowing you are doing it for your kids and grand kids also along with other health benefits that are there as side effect.

It's been my experience in the ''more balding'' days. Whenever i got on the sun, many symptoms disappeared and scalp benefited as well. But i doubt it's only because vitamin D - prostate connection; rather for the increasing blood flow and overall inflammation reduction, and also because the fact i was active and moving and let my worries far behind. Balanced neurohormones have with no doubt role in it as well. I think decreased GABA can be marker for scarring alopecia if i am not mistaken. The same (emotional/neurohormonal) applies to greying as well.

It's also fair to analyse also environment where people are put to get a bigger picture towards what's the epigenesis. Let say office job, or industry working with chemicals -  increasing intoxification, etc... Many times environment is mostly against the human nature. At the end, other diseases have the same aspect and predisposition, but pain a bit less, since are not so big destroyers of personal image (breast cancer equivalent for a female) - and i agree with your arguments of self perception like totally.

All this means you can have hair until very late regardless of predisposition, or act to lose it tomorrow. All epigenetics. Also sun exposure is worth more than for vitamin D synthesis reasons and some frequencies don't need uncovered skin to benefit. IR spectrum for example. And for those working outside, hair provides UV rays protection and thermoregulation of the scalp/brain, which is another look at it...

Keanoseg wrote:
Yes but the genetic component of all of this, is how much a follicle is responsive and sensitive to certain things. And that enviroment can be manipulated.

Totally agree. If you found a mechanism which could impact that sensitivity to the free androgen concentration, you could theoretically stop the loss from happening. If the steroid receptors are upregulated, there isn't much that's going to stop the cascade after the hormone-receptor interaction. You'd have to have something that would act as a blockade of the resulting cascade. So, whatever mechanism you found, it would either have to lower levels of the steroid receptor or block the cascade that results from it. OR, it would have to antagonize the hormone-receptor interaction ONLY in the target tissue. Drugs like fin do this now, but they are systemic and we know the problems that occur with this.

Ok let's say this happens. You alter the enviroment that's causing problems. You reduce the amount of androgen conversion activity in the area and reduce the inflammatory cytokines, apoptosis expression and all else, that are in a tied upregulation connection with them and inflammation and hypoxia. You also reduce glandins and other things aside inflammation that may stimulate calcification etc. You reduce the androgen receptor activity itself, all to normal healthy levels. And antagonistic expressions should rise up. You initiate the process of reversing fibrosis and whatever else may be the problem, through regenerative and proliferative properties of various pathways through fibroblasts and keratinocytes and possibly something else, like stem cells with differentiative properties. You also influence or reactivate signalling pathway cascade that is synergistic with the enviroment change, because that is the only kind of enviroment it can operate in. What does that translate to?

Keanoseg wrote:Ok let's say this happens. You alter the enviroment that's causing problems. You reduce the amount of androgen conversion activity in the area and reduce the inflammatory cytokines, apoptosis expression and all else, that are in a tied upregulation connection with them and inflammation and hypoxia. You also reduce glandins and other things aside inflammation that may stimulate calcification etc. You reduce the androgen receptor activity itself, all to normal healthy levels. And antagonistic expressions should rise up. You also influence or reactivate signalling pathway cascade that is synergistic with the enviroment change, because that is the only kind of enviroment it can operate in. What does that translate to?

The testosterone hormone is produced directly by the Sertoli cells of the testicles from cholesterol precursors and also to an extent by conversion of DHEA produced by the adrenal glands. Testosterone is further reduced by 5-a reductase to its hydrated form, DHT. This happens in many tissues, including peripherally in the skin, to varying degrees in different individuals.

The great majority of endogenous testosterone is bound up in a protein complex called sex hormone binding globulin, SHBG. Circulating in this form, the testosterone cannot be converted. The fraction of total testosterone which is not bound is considered 'free', and it is able to be reduced to DHT or aromatized into estrogen.

When testosterone encounters a cell membrane, it diffuses through it into the cytosol where it can be reduced to DHT. Both testosterone and DHT are then able to interact with intracellular steroid hormone receptors. These are like little satellites floating around the cell. When either of these binds with the AR (androgen receptor), the hormone-receptor complex (called a dimer) moves to the nucleus and begins a cascade of signals that ultimately changes (turns on or off) certain genes. Sometimes the dimer can modify another enzyme which goes to the nucleus and creates more signalling, in this way hormones can have polygenic effects.

Basically, (1) hormone enters cell > (2) hormone undergoes reduction > (3) hormone interacts with receptor > (4) dimer promotes a signal cascade of other molecules that translocates to nucleus and effects genetic expression

This is grossly simplified. In the case of MPB, there are many other hormones which cross-talk with this process and cause some things to happen more, some to happen less. The signalling cascade occurring due to testosterone binding is complex. Many different factors are produced as secondary signals. Things like COX activity can modulate the entire process and speed it all up, for example. What we have to respect is that after step (4), there are many different pathways that occur. In certain tissues, the pathway is anabolic and promotes inflammation and protein synthesis (ala muscle). In the hair follicle, there are apoptotic signals that occur which promote cell death.

Fundamentally, there would be six different "points of contact" that you could hope to beneficially alter the process. Just keep in mind that at this point you could not alter the genes themselves. We also aren't going to change the activities of the hormone-receptor complex. We'll assume that if hormone binds, the signal will be sent. 6 points of contact:

(1) Lower absolute levels of the steroid hormones. No hormone, no messenger. (Not a good option)
(2) Lower levels of the steroid receptors. (A possibility if and only if you could restrict it to target tissues. Systemically it would be a disaster)
(3) Antagonize the hormone from interacting with the receptor. (Siimlar to 2, if you can relegate this to the target tissue wonderful)
(4) Block the 5-ar enzyme which reduces testosterone to DHT. (Fin/Dut, again the problem of not being able to target certain tissues)
(5) Use some substance or chemo-mechanical process to block the signalling cascade that occurs after the hormone binds to the receptor.
(6) Promote another signalling cascade that directly opposes the apoptotic signal from testosterone.

ANY of these could potentially have hair growth properties. The rub is that testosterone has many effects throughout the system and blockading its signalling systemically is exactly why current drug regimes are dangerous. To do this successful would mean having effects only in the target tissue of the scalp, which is more difficult that it might seem given that these signalling chains and the hormones and receptors are pretty ubiquitous through the body (how will our method be selective to operate where we want it and only there?).

For example, lowering levels of the steroid receptors in the follicle would promote hair growth. But you'd have to demonstrate a mechanism for doing this in that tissue, and that tissue alone. You'd run into major problems doing this systemically. (5) or (6) would be excellent IF AND ONLY IF you could accurately map all of the signalling cascades that occur after testosterone signalling. There are major efforts to do this now, and there is probably a great deal of information which could be compiled from academic sites, Google scholar, and various hairloss forums that could help you to draw a rudimentary map of the signals that are sent by the testosterone-receptor complex. Keano, you mentioned some of these in your last post. If (5) or (6) were the strategy you wanted to take you'd have to make a schematic of these cascades and decide where you were going to intervene, what effect that would have on the tissue (besides promoting hair growth), and if your method would viably block that part of the chain (whether it be DKK-1, for example, or another player) in the scalp and nowhere else.

I know that you are interested in the mechanical properties of DT. If you could demonstrate that some mechanochemical stimulus from DT was able to block the apoptotic cascade and at what level it intervened, you'd have something.

One thing which complicates the entire picture is that this "overly sensitive" androgen receptor (AR) doesn't interact only with testosterone/DHT. Take a look at the following transduction pathways. You can see all of the other factors which interact with the AR.



The following image shows the signalling pathway for testosterone, MTOR for the protein synthetic pathway you'd find in muscle. Keep in mind this does not show all of the inflammatory products the AR is able to effect.



One schematic showing the AR as only one potential pathway contributing to MPB, and with fibrosis and apoptosis as causes of permanent hair loss:



The Wnt pathway has gotten a lot of attention. It is involved with stem cell maintenance and survival. A poster named Flynn at another forum put together the following diagram with his hypothesis, just to give you an idea of how these processes have to begin to be picked apart if cascade blockade is your goal (this one also implicates COX-2, PGD2, and GPR44 just to add to the signalling madness):

When I said reduce androgen conversion I didn't mean on T in the testicles rofl . I began to write a REALLY long post in response to all this but it ended up being really messy, I wanted to show the interconnection and correlation effects of all these things that are in the models, other biochemical processes, and what I talked about but there's just too much of it to display it in a text message, it's impossible. I constantly have to come back to something and connect it with something else, and do so for every point . I came to point 14) and I realised I'm not even close to nearly half way done. I don't know how to 100% map this without having a lab and being able to measure it and knowing the exact chronology between an input and reaction of these events. I could theoretically show it in your first,third and fourth model. What I believe can be explained, is your (6), (3) in a specific way and (5) in a very specific way.

Keanoseg wrote:When I said reduce androgen conversion I didn't mean on T in the testicles rofl . I began to write a REALLY long post in response to all this but it ended up being really messy, I wanted to show the interconnection and correlation effects of all these things that are in the models, other biochemical processes, and what I talked about but there's just too much of it to display it in a text message, it's impossible. I constantly have to come back to something and connect it with something else, and do so for every point . I came to point 14) and I realised I'm not even close to nearly half way done. I don't know how to 100% map this without having a lab and being able to measure it and knowing the exact chronology between an input and reaction of these events. I could theoretically show it in your first,third and fourth model. What I believe can be explained, is your (6), (3) in a specific way and (5) in a very specific way.

actually,
heart disease as a cause of hair loss would be the same as the calcification theory,
put forth by Bellanger in the 1940s, who analysed peoples scalps.

And of course that would be connected to k2, vitamin d and calcium ratios.

iuyyighghghgkh I'm talking about something else, other than nutrition. Locally.

Keanoseg wrote:iuyyighghghgkh I'm talking about something else, other than nutrition. Locally.

summarise your theory

Read my previous posts and 102's message. I am talking about DT, not balding as such. To explain it in total terms with all the mechanisms it would take an entire page of text and it still wouldn't be measured in the lab. Model is also hard to make, I really can't do this alone but I know it can be done. Sorry we intruded your thread here lol.

Keanoseg wrote:Read my previous posts and 102's message. I am talking about DT, not balding as such. To explain it in total terms with all the mechanisms it would take an entire page of text and it still wouldn't be measured in the lab. Model is also hard to make, I really can't do this alone but I know it can be done. Sorry we intruded your thread here lol.

Try to.

How about, I send you about 50 studies for start, then you summarize them here as one process?

Keanoseg wrote:How about, I send you about 50 studies for start, then you summarize them here as one process?

studies on what ?

Well what do you think lol?

woops, it was actually "Dr. Hoelzel's "ivory dome" theory of baldness."

not the one i mentioned

iuyyighghghgkh wrote:woops, it was actually  "Dr. Hoelzel's "ivory dome" theory of baldness."

not the one i mentioned

I think that was atributted to bone growth anabolic effect. What's interesting though, is that there also might be vascular and soft tissue calcification.

Keanoseg,

As the time permits, you ought to just begin putting a document together compiling all of your information into something cohesive. Then when you're ready just post it all in a single thread here. You've communicated with me that most of it is present in the DT thread, however, given people's limited ability to sift through all of the information when its fragmented here and there, it might be more effective if it were all in one place. But I do realize that's a time sink to compile.