Involvement of Mechanical Stress in Androgenetic Alopecia

Abstract



Context:

Androgenetic alopecia (AGA) is a frequent disorder characterized by progressive hair miniaturization in a very similar pattern among all affected men. The pathogenesis is related to androgen-inducible overexpression of transforming growth factor β-1 from balding dermal papilla cells, which is involved in epithelial inhibition and perifollicular fibrosis. Recent research shows that hair follicle androgen sensitivity is regulated by Hic-5, an androgen receptor co-activator which may be activated by the mechanical stimulation. Moreover, the dermis of scalp susceptible to be affected by AGA is firmly bounded to the galea aponeurotica, so the physical force exerted by the occipitofrontalis muscle is transmitted to the scalp skin.


Aims:

To know whether mechanical stress supported by hair follicles is involved in AGA phenomenon.


Materials and Methods:

It is performed with a finite element analysis of a galea model and a schematic representation of AGA progression according to Hamilton–Norwood scale in order to establish the correlation between elastic deformation in scalp and clinical progression of male pattern baldness.


Results:

The result was a highly significant correlation (r: −0.885, P < 0.001) that clearly identifies a mechanical factor in AGA development.


Conclusions:

All these data suggest that mechanical stress determines AGA patterning and a stretch-induced and androgen-mediated mechanotransduction in dermal papilla cells could be the primary mechanism in AGA pathogenesis.

Keywords: Androgenetic alopecia, galea aponeurotica, mechanical stress, mechanosensitivity


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INTRODUCTION

Male androgenetic alopecia (AGA), also called male pattern baldness, is a frequent disorder characterized by progressive hair and follicular miniaturization in a very similar pattern among affected men that is classified according to the Hamilton–Norwood scale.[1,2] Genetic predisposition, androgens, and aging are closely related to AGA, but pathogenesis has not been clarified yet.

Dermal papilla is considered a key element in AGA development[3] and thickening and hyperplasia of the dermal sheath is the only universally accepted histopathological evidence in AGA.[4] Both dermal papilla and dermal sheath are considered as a functional unit[5] which constitute the dermal component of the hair follicle, and its metabolism is bidirectional in the anagen-catagen transition.[6] The alteration of this tissue remodeling may cause an excessive collagen network that would not be fully digested later, resulting in physical blocking of the hair canal by a fibrotic process called perifollicular fibrosis.[7,8,9]

Transforming growth factor β-1 (TGFβ-1) is related to fibrosis by upregulating extracellular matrix (ECM) synthesis in many tissues[10] and it causes epithelial inhibition in hair follicle,[11] so it seems to play a fundamental role in AGA pathogenesis. Moreover, TGFβ-1 overexpression is induced by androgens in balding dermal papilla due to enhanced androgen sensitivity.[12] Inui et al. have shown that this androgen sensitivity of dermal papilla cells is regulated by androgen receptor (AR) co-activator Hic-5/ARA55, a focal adhesion associated protein belonging to the family of paxillin.[13] Although Hic-5 is located predominantly in the focal adhesion, it can also be found in the nucleus[14] where it could directly affect TGFβ-1 gene expression in association with AR and dihydrotestosterone. Interestingly, a triggering stimulus that can alter the inactive standby status of Hic-5 is the deformation of the cytoskeleton by physical forces;[15,16] therefore, mechanical stimulation can promote overexpression of molecular signals implicated in AGA pathogenesis.

This fact takes sense if it is considered that scalp skin susceptible to be affected by AGA presents unique anatomical and biomechanical features. Regardless the pattern or degree of severity, AGA is always limited to the skin overlying the galea aponeurotica. This is a thin and relatively inelastic tendon-like tissue sheet that communicates the frontal and occipital bellies of occipitofrontalis muscle.[17] Balding scalp skin is firmly bounded to galea by fibrous rigid subcutaneous layer, so elastic deformation affecting the galea is shared by the three upper layers as a structural unit[18] [Figure 1], whereas the remaining scalp skin freely slides over deeper layer, with low strain transmission to hair follicles and unaffected by AGA.

I believe that MPB is brought on by aging and stress.

You ever wonder why people who go bald late in life don't do so earlier? It is because their scalps have not lost their subcutaneous fat layer, this is what protects the follicles of young people. It is shown that poor blood flow from a tight and thin scalp will cause the MPB area to be hypoxic, it is known that the conditions of scalps with MPB is also hypoxic in areas where hair loss is occurring. Moreover, the conversion of testosterone to DHT is favoured in low-oxygen environments, making the hypoxic, tight and balding scalp the perfect place for even more DHT. If oxygen is restored the testosterone is converted into lovely skin-plumping estradiol.

I believe this is why Retin-A and maybe scalp peels work, by replenishing the protective layer.

Thank you, SoloDomo.

Wasn't their some proceedure done on people that released or removed or did something to the galea, meaning no tight scalp, but that the end result was no difference?

Galeatomies? I don't really have much info on their success stories but I can say that the botox treat which basically does the same thing worked

Mechanical force is a contributory factor. You might want to look up 'pressure alopecia', OP. I've mentioned previously how longstanding pillow compression can squash follicles against the hard mass of the skull, thus leading to something akin to a crush injury. However, this is only one of many factors which I believe adversely affects growth factors and wound healing.

Here is a PDF which explains how bacterial infections increase under hypoxic conditions: http://onlinelibrary.wiley.com/doi/10.1111/febs.13270/pdf

Bacterial infections cause tissue to become highly immunoreactive, this leads to the immune system attacking infected cells, which then causes a substance called muramyl peptide to be released from bacterial cell walls. MP's cause an increase in the IL-1 cytokine, which, in turn, triggers the release of PGD2.

Both IL-1 and PGD2 are potent inhibitors of human hair growth.

Xenon wrote:Mechanical force is a contributory factor. You might want to look up 'pressure alopecia', OP. I've mentioned previously how longstanding pillow compression can squash follicles against the hard mass of the skull, thus leading to something akin to a crush injury. However, this is only one of many factors which I believe adversely affects growth factors and wound healing.

This theory is incorrect, I have slept on my right side my entire life (right side of face planted on the pillow) and my right temple is in much better shape than my left temple.

Themanofmankind1 wrote:

Xenon wrote:Mechanical force is a contributory factor. You might want to look up 'pressure alopecia', OP. I've mentioned previously how longstanding pillow compression can squash follicles against the hard mass of the skull, thus leading to something akin to a crush injury. However, this is only one of many factors which I believe adversely affects growth factors and wound healing.

This theory is incorrect, I have slept on my right side my entire life (right side of face planted on the pillow) and my right temple is in much better shape than my left temple.

Well, pressure alopecia is a proven condition, therefore it has some scientific merit. I have reported inflammation / increased thinning countless times from sleeping on one temple more than the other, in the same way I have experienced inflammation from having my crown pressed against a solid surface for too long. When cells suffer compression, they become more prone to bacterial infection, and therefore enter into a highly immunoreactive state. Yet, this issue is more prominent in follicles with a higher yield of androgen receptors. high testosterone levels are believed to promote increased susceptibility to bacterial infection, due to slowed immune response.

Hello Xenon, yes, I have indeed been a lurker for.just under a year so I can say I have been witness to many a legendary argument with Complex, I do understand pressure alopecia and can definitely see the logic (my uncles loss started when he wore tight hats, Im pretty sure that may not be a myth). I believe that MPB is definitely multifactorial but ultimately I believe the natural aging of the scalp skin to be what starts it, I believe that DHT speeds up this aging.

My reason for believing this is as follows:

1. If DHT causes baldness in all who have the baldness gene, how come some teenagers who will go bald later don't bald immediately despite having very high T and DHT? I believe this is because they have healthy well supplied scalp tissue protecting their follicle and low stress allows for good circulation (this is very crackpot and speculative).

2. If derma rolling regrows hair, why isn't it lost again immediately due to the same amount of DHT? This is because the derma rolling causes a massive release of growth factors which replete all of the lost scalp tissue.

What I can't explain:

1 . I do not understand how I can fit PGD2 into this, could it be it is used as an immune response as you say, or could it be the driving force behind the tissue damage?

Yes, I think gene expression determines how many receptors will ultimately upregulate in hair follicles (in accordance with DHT levels). Some experience rapid diffuse thinning from an early age, whereas with others the condition progresses more slowly. Therefore I can only imagine that gene expression determines how many receptors will upregulate per follicle... The higher the amount, the more rapid the hairloss, I'd imagine.

For instance, I have some follicles in the bald areas of my temples which have continued to produce terminal hair, yet the majority of surrounding follicles have miniaturized. Why could this be? I can only imagine, for whatever reason, these particular follicles have not been genetically selected for the upregulation of androgen receptors, thus dodge an attack from the immune system.  

And if we transplant non-galea hair into balding areas, it continues to grow without being subject to an immune response. Why? It must be due to these follicles having reduced numbers of androgen receptors, thus making them less susceptible to bacterial infection and inflammation.

Without doubt genetics and androgens are a factor in MPB because many female to male transsexuals go bald on T therapy, whereas others don't. The answer, IMO, can only be explained in terms of genetic upregulation of AR's in certain follicles.

Also, I honestly don't know how credible dermarolling is. I've heard some say it works, and others say it caused worse hairloss. So the jury is out on that one.

As for PGD2, I've read that that it tends to increase in accordance with pro-inflammatory cytokines implicated in hairloss (IL-1 and IL-6). According to the research, high PGD2 levels indicates bacterial infection of cells, and it is released to make us sleep so that our bodies can recover better. Sleep deprivation apparently leads to increased bacterial infection, immune attack, and PGD2. But I believe the precursor to all of this is DHT because the hormone is linked to increased bacterial / fungal infection.

And what you said in your second post about depleted subcutaneous fat layers, I believe holds merit. Fat, in part, acts as a cushion to cells, thus preventing them from being crushed against the hard mass of the skull, this is why we have so much on our asses, so that we can sit down and relax without the threat of crush injury to tissue. In the non balding areas of the lower back and sides of the head, there is an abundance of this fatty tissue, but surprisingly little in the bald prone areas, therefore it's little wonder why the latter more readily suffers mechanical overload when pressed against a pillow or wearing tight fitting headgear.

I have always found issue with the whole "pre-programmed follicle" thing as I know many men including y grandfather who have a relative with hairless yet somehow have none them self, not only that, I also know that in some cases hair transplants do fall out eventually.

I have always believed that it is the scalp environment being hypoxic and not an issue with the follicle itself

SoloDomo wrote:I have always found issue with the whole "pre-programmed follicle" thing as I know many men including y grandfather who have a relative with hairless yet somehow have none them self,  not only that, I also know that in some cases hair transplants do fall out eventually.

I have always believed that it is the scalp environment being hypoxic and not an issue with the follicle itself

Well, your choice what you feel to be true. Hypoxia definitely does lead to increased inflammation for the reasons mentioned, but I don't know if increasing oxygen is enough to reverse baldness. You may have read previous posts of mine where I've mentioned that oxygenating my bedroom always causes inflammation to disappear, but has not been enough to regenerate follicles. The only joy I had in regrowing hair naturally was by abstaining from masturbating for several months and preventing inflammation as much as possible. Interestingly, when I abstained, this seemed to really reduce inflammation in my temples. I have also read that fin users also report decreased inflammation. Therefore, I can only assume that DHT is a prominent inflammatory precursor.

Xenon: "I have also read that fin users also report decreased inflammation. Therefore, I can only assume that DHT is a prominent inflammatory precursor."

Prior to fin my scalp would occasionally redden and I'd get a painful itch. I could also grow more facial hair than most men could in a week, in only a single day. A sign that my DHT levels were through the roof. So, I think your assumptions are correct.

Xenon, I know a way you can masturbate and not lose hair, I found this as every time I did the shuffle my acne would flare up and my skin would be shit. Take about 30mg of zinc and 800 iu vitamin e after ejaculating, the zinc is clinically proven to lower prolactin levels and vitamin e prevents any oxidation occuring.

Also, I just thought, what if pgd2 is released in the scalp as the bodies natural anti-hypoxia? It is proven that pgd2 is a vasodilator, perhaps the body releases it to restore blood flow at the expense of our hair?

Odin, thanks for feedback. As mentioned, androgens must definitely be involved, hence MPB in F2M transsexuals.

SoloDomo, thanks. I remember taking zinc supps many years ago, and they caused my skin to become very healthy looking, not to mention causing my hair to thicken up considerably within two weeks. Yet, I over did it with the dosage and started experiencing severe cramp pains in my calf muscles. No idea why that was.

re: pgd2, the research states it acts as a vasodilator and inflammatory mediator for th2 cytokines. Is it beneficial? Well, that Swiss guy used Seti to block the CRTH2 receptor, and reported regrowth, so it would seem it acts as an antagonist for hair growth. I think Bov5 is also reporting regrowth from Swiss' protocol.

No problem xenon, Im glad it's not just just me who was helped by zinc, it's ok to have more zinc depending on how much copper you get. In my area, the water is very soft so I think more copper is present, allowing me to take up to 120mg without sides.

It is 100% guaranteed that pgd2 is VERY BAD for your hair, I believe that the body uses it to keep the blood flowing in your scalp, neglecting hair.

I think pge2 works as a vasodilator, only it doesn't wreck your hair

Yeh, additionally, and as mentioned many times in the past, it seems that one of the main obstacles in regrowing hair is deficiency of CD34+ / CD200 progenitor cells. From what I've read, these cells are responsible for the proliferation of terminal hair growing cells (matrix cells). So, not only is chronic inflammation an issue, but progenitor numbers decline within the bulge. All of these issues (combined) seem to work towards the manifestation of hairloss, so this is why I can't help but occasionally wonder if the condition is a natural secondary sex characteristic triggered by androgens and genes, in the same way some men have the androgen receptor genes for a hairy chest, squared jaw, etc.

If it is a natural secondary sex characteristic, then what could the purpose of MPB be? Why would the body want to purposely rid itself of scalp hair in adulthood?

Perhaps it is done to save blood, males are stronger and use more energy, in people who have been bald for ages there isnt much inflammation, it could be hair is sacrificed?
Just a fun thought

I'm going to look into taking niacin flush

Who knows? If you think about it, testosterone is the steroid which turns us from boys to men, so that we have the physical / mental strength to fend for ourselves and survive in the big bad world. Therefore this makes me wonder if MPB was some sort of additional secondary sex characteristic which further aids our survival in the world. I wondered if this "bonus" sex characteristic was some sort of evolutionary alarm system which arisen at some point in history due to various and ongoing environmental threats to man as he was out hunting and gathering.  

For instance I find it extremely curious that a broad range of insults specifically lead to an inflammatory response specific to scalp follicles. These stressors are: anxiety, extremes of temperature (hot or cold), infection, intense exercise, sleep deprivation, food allergies, exposure of the cell to toxins (ethanol, arsenic, trace metals), radiation, starvation, hypoxia, dehydration, etc.

So to generally summarize: 1) Production of testosterone signals the system that we are entering into adulthood and need to now look after ourselves in the big bad world, hence anabolism of bones, muscles, brain 2) This then triggers a gene which puts the survival alarm system in ready mode for any potential threats 3) Any stress to the system sets off this alarm system by causing follicles to inflame. This repeated pattern of pain helps us recognize the insult  4) Loss of hair represents a chronically stressed system and our failure to recognize and prevent what was causing us harm.

Of course this is just a personal theory, I just think it holds some weight because various stressors seem to trigger inflammation specific to follicles of the galea. And when that stressor has been recognized and removed, so is the inflammation. Coincidence?

Edited: It could also be that DHT specifically triggers the gene which activates this survival alarm system. As mentioned earlier, when DHT levels are lowered so too is the immunoreactive state of these follicles. This may be one of the fundamental reasons why some men throughout history developed this sex characteristic and others didn't.

I 100% certainly believe that the idea that emotional stress is not an MPB trigger is stupid. For example, while my paternal grandfather kept calm and was rarely stressed, my father was plagued by chronic anxiety and stress characterised by stammering shaking. Guess who receded the most?

Yep, this is why I can't play video games because of elevation of stress hormones, which always cause my scalp to inflame. I also become very agitated and aggressive from playing games too long. CS also said that he experienced scalp inflammation when playing video games; I have since encountered other people across the internet who have noticed a pattern of scalp inflammation / hair loss from gaming too long. I can only put it down to elevation of stress hormones and cytokines.

And what you mention about stammering seems to be a recurring theme on the boards. I developed a terrible stammer in my early 20's from a shitload of stress, but thankfully, I managed to cure it many years later.

Here's one of many studies on the stress response induced by video games, they cite music and sound effects as the source of stress. Maybe.

Physiological stress response to video-game playing: the contribution of built-in music.
Hébert S1, Béland R, Dionne-Fournelle O, Crête M, Lupien SJ.
Author information
Abstract
Recent studies on video game playing have uncovered a wide range of measurable physiological effects on the organism, such as increases in cardiovascular activity and breathing responses. However, the exact source of these effects remains unclear. Given the well-known effects of sound on physiological activity, especially those of noise and of music, and on the secretion of the stress hormone cortisol in particular, we hypothesized that music may be a major source of stress during video game playing. We thus examined the effect of built-in music on cortisol secretion as a consequence of video game playing. Players were assigned quasi-randomly to either a Music or a Silence condition. Four saliva samples were taken, that is, after practice (T1), immediately after having played for 10 minutes (T2), 15 minutes after the end of the experiment (T3), and 30 minutes after the end of the experiment (T4). The results show that the Music group had significantly higher cortisol levels at T3, that is, when cortisol levels are assumed to reflect the stress induced by the game. These findings suggest for the first time that the auditory input contributes significantly to the stress response found during video game playing.

Hmm, stutterer, check. Video game addict, check(formerly). No wonder I lost nearly all my hair in under a year.

If we're going to discuss the function of baldness as a secondary sex characteristic, I think one of the most compelling clues is the general reaction of the female sex towards it. Remember we're evolved to only accomplish two things: survive, and reproduce. And reproduction was not something that people waited so long to do. The majority of males eventually end up as worker bees to aid in survival, but how, and when does this transition take place?  The new fad is to claim alphas are getting all the women but its really just men at their peak doing their thing.

Back to masturbation. It's been shown that fapping and watching porn actually tricks your body into thinking it's having real sex with real women. If your body thinks its mating 1-3 times a day(for severe porn addicts) is it unreasonable to suggest that nature has a way to ensure that there is some diversity in what genes are passed on?

The Chinese also spoke of abstaining from ejaculation claiming it is 'life force' and this may not be far from the truth. Masturbation may send signals that put simply state 'I've spread my seed enough, my reproductive purpose is complete...' and then certain markers like balding become more prominent that a lot of women(certainly not all) tend to avoid.

But, this is just me entertaining the masturbation theory. It's not something I'm 100% behind but perhaps a method to curb aging is to stop tricking your body you're spreading your seed so often. What would add to this theory is if we can observe anything else from those who are addicted to porn.

That really is not a bad idea, very fascinating

I have never had or stammer or a bad shake but it's funny you mention this as I have always been incredibly tense in situations where I'm judged (e.g. playing the guitar), coincidentally I do often play video games. Could these be a link? I find it odd because I play strategy games like CK2 the most and they aren't the most stressful games ever.

Another thing I will add, how come taller men appear to go bald more often, my maternal grandpa is 5'7 and has some kind of NW1.5 temples but a NW4 crown and vertex while his son my uncle is a full NW7 at 6'2, could this be a link?

Also, I do think skull shape determines rusk of MPB, every square faced and flat skulled man I have seen has lots of hair, my dad has a very round and curved forehead but the back of his head is angular and square and has no crown loss

Yeh, guys, I think the hub of the problem is the baldness gene. I have come across guys from all walks of life... some who are chronic masturbators who haven't lost any hair, some with large bulbous craniums who haven't lost hair, some who wear tight hats every day who haven't lost hair, etc, etc...some guys just don't bald no matter what, and I can only attribute that to strong recovery factors determined by genetics.

I personally think that these things only become problematic if you have the gene, which programs follicles to enter into an immunoreactive state. It seems to me that the baldness gene not only cause follicles to readily inflame from various stressors (in a predictable pattern), but it also does another thing: signals progenitor cells to decline within the bulge, which consequently stops matrix cells from proliferating around the papilla. This IMO is generally the reason why MPB is a one way street and follicles don't regenerate after miniaturizing from prolonged episodes of inflammation.

I mean, I don't know of any MPB sufferer who has lost his hair then have it regrown *naturally* at a later point in life. We hear of this oftentimes happening with alopecia sufferers, but never MPB. Therefore I can't help but think that a baldness gene is behind this. This is not to say that hair cannot be recovered naturally (follicles are not dead), they are just genetically programmed to remain in the telogen phase after undergoing auto-immune attack.

Edited: Here's a pic of UK prime minister David Cameron. He has a large bulbous forehead, but his hair is in generally good condition... no thinning per se. From what I can tell, he's always had a large bulbous forehead:



And here is when he was young:

Oh and without hijacking your thread, OP, check out Nicolas Cage's hairline in his youth. Who'd have ever thought he'd have gone bald a few years down the line... same with Billy Zane, Prince William, as typical examples of balding men with short foreheads.