New clinical trial intended to prove the Androgenetic Alopecia theory.

[freakout]

I'll bet my balls they won't get any positive results from topical RU.

I don't understand. People with Androgenetic Alopecia do get results with RU don't they?

Unless, it's FDA approved, consider what your read as hearsay. I'm referring to topical anti-androgens. Remember, these are not the same when applied topically versus oral.

Think about it. Merck has "known" for about two decades that "DHT induces miniaturization". Seems logical that they would have gone to the process of testing topical anti-androgens. WIth billions in resources, it would be a cinch to produce and test those. Why is there none? THe answer is simple: it doesn't work that way.

Freakout, does what Darkdays says in another thread backup your theory and do you agree with him?

Not necessarily. Atherosclerosis is merely associated as shown by studies. They never proved causation. But the studies do imply common contributing factors. Note the critical difference between the underlined words. "Causation' requires a very strict set of parameters.

Note, not all men with atherosclerosis are balding and many balding men are free from atherosclerosis.

I think he meant 'arteries' when he said 'veins'? Veins are never affected by atherosclerosis.

 

[Bryan]

I don't understand. People with Androgenetic Alopecia do get results with RU don't they?

Unless, it's FDA approved, consider what your read as hearsay. I'm referring to topical anti-androgens. Remember, these are not the same when applied topically versus oral.

He said "RU" in plain English, dumbbell. Everybody knows that RU58841 is used as a topical antiandrogen.

Think about it. Merck has "known" for about two decades that "DHT induces miniaturization". Seems logical that they would have gone to the process of testing topical anti-androgens. WIth billions in resources, it would be a cinch to produce and test those. Why is there none? THe answer is simple: it's doesn't work that way.

There HAVE been successful experiments with topical antiandrogens in both humans and stumptailed macaques, stupid. Why are you pretending not to know about them? Are you just "playing-dumb"?

 

[freakout]

Everybody knows that RU58841 is used as a topical antiandrogen

Does 'everybody' include the FDA? Where is the "study"? What brand is topical RU being sold? Why hasn't Merck sold such a topical?

 

[optimus prime]

Everybody knows that RU58841 is used as a topical antiandrogen

Does 'everybody' include the FDA? Where is the "study"? What brand is topical RU being sold? Why hasn't Merck sold such a topical?

If you believe the DHT affects the area around the follicle but not actually the follicle then surely topical sprio or similar products should work for your theory also? Why don't they work? Or why do they work but on such a small scale?

If DHT is blocked from the scalp using a topical then hair loss will stop, even with your theory. Is that right?

 

[Bryan]

Everybody knows that RU58841 is used as a topical antiandrogen

Does 'everybody' include the FDA?

Yes.

Where is the "study"?

There are probably close to a dozen or so studies on RU58841. Do a search on PubMed to find them.

What brand is topical RU being sold? Why hasn't Merck sold such a topical?

The only places I know of for sure that produce and sell RU58841 are some Chinese companies, and one Canadian company. Merck didn't design or invent RU. Some doctors at a French company did that.

 

[freakout]

Show them Bryan. Thanks.

If you believe the DHT affects the area around the follicle but not actually the follicle then surely topical sprio or similar products should work for your theory also? Why don't they work? Or why do they work but on such a small scale?

If DHT is blocked from the scalp using a topical then hair loss will stop, even with your theory. Is that right?

I didn't say 'around'. I said:

... Remember the mouse study. Androgens' affect follicles indirectly...

It's the action of androgens in the large muscles in the body that affects scalp hair follicles - the very reason finasteride has to be taken orally...

It's a paradox, right? The effect is so far from the follicles. It's going to present a paradox to you until you read the book completely. It even explains how the baldness patterns are formed.

 

[hairhoper]

...

 

[squeegee]

Cutaneous immunopathology of androgenetic alopecia.
Young JW, Conte ET, Leavitt ML, Nafz MA, Schroeter AL.
Source

Department of Dermatology, Grandview Hospital Medical Center, Ohio University College of Osteopathic Medicine, Dayton.
Abstract

Male pattern baldness is assumed to result from a combination of normal serum concentrations of androgen and an appropriate genetic background. To study whether inflammation contributes to the development of androgenetic alopecia, direct immunofluorescence and dermatopathologic studies were performed on biopsy specimens from bald scalp of patients, with specimens from uninvolved scalp of these patients or from scalp of volunteers who were not bald serving as controls.

Granular deposits of Immunoglobulin M or C3 (or both) were found at the basement membrane in 25 (96%) of 26 study patients and 1 (12%) of 8 control subjects. Granular C3 was also deposited on eccrine myoepithelial cells in 8 (31%) of 26 study patients, but no control subjects. Porphyrins were found in the pilosebaceous canal in 15 (58%) of 26 study subjects and in 1 (12%) of 8 control subjects. These results support an inflammatory pathogenesis of androgenetic alopecia. Propionibacterium acnes is known to produce porphyrins. Ultraviolet radiation may excite microbiologic porphyrins that could activate C3 and, subsequently, the complement cascade producing inflammatory mediators.


Inflammation in androgenetic alopecia

Years of research have led to the conclusion that androgenetic alopecia may be a result of an alteration in the hair growth cycle and/or a premature aging of the pilosebaceous unit. The etiology of androgenetic alopecia has been defined as multifactorial or even polygenic in nature. The fact that the success rate of treatment with either antihypertensive agents or modulators of androgen metabolism barely exceeds 30 percent, has led to some researchers to propose the possibility of other pathways that mediate this form of hair loss.

Hair follicle inflammation in androgenetic alopecia

The new focus, therefore, is the implication of various activators of inflammation in the etiology of androgenetic alopecia. An early study referred to an inflammatory infiltrate of mononuclear cells and lymphocytes in about 50 percent of the scalp samples observed. Jaworsky et al. subsequently in 1992 referred to an inflammatory infiltrate of activated T cells and macrophages in the upper third of the hair follicles, associated with an enlargement of the follicular dermal-sheath composed of collagen bundles (perifollicular fibrosis), in regions of actively progressing alopecia. Whiting has documented that horizontal sections of scalp biopsies indicated that the perifollicular fibrosis is generally mild, consisting of loose, concentric layers of collagen (a fibrous protein that makes up connective tissue) that must be distinguished from cicatricial alopecia. Another study conducted on 412 patients (193men and 219 women) showed the presence of a significant degree of inflammation and fibrosis in at least 37 percent of androgenetic alopecia cases.

The location of the infiltrate near the infrainfundibulum clearly differentiates androgenetic alopecia from alopecia areata, which is characterized by infiltrates in the bulb and dermal papilla zone. The term ‘microinflammation’ was proposed by Mahe and colleagues because the process of inflammation in androgenetic alopecia adopts a slow, subtle, painless and lethargic course, in contrast to the inflammatory and destructive process that has been seen in the classical inflammatory scarring alopecias.

The significance of these findings has remained controversial. However, only 55 percent of male pattern androgenetic patients with microinflammation had hair re-growth in response to Minoxidil treatment, which was less than the 77 percent of patients with no signs of inflammation, suggesting that, to some extent, perifollicular microinflammation may account for some cases of male pattern androgenetic alopecia which do not respond to Minoxidil.

Inflammatory phenomena in pattern baldness

An important fact to be established is how the inflammatory reaction pattern in androgenetic alopecia is generated around the individual hair follicle. Inflammation is regarded as a multi-step process which and is assigned to a central major mediator or pathway. Mahe et al believe that the presence of a perifollicular infiltrate in the upper follicle near the infundibulum points to the fact that the primary causal event for the triggering of inflammation might occur near the infundibulum.

On the basis of this localization and the microbial colonization of the follicular infundibulum with Propionibacterium sp., Staphylococcus sp., Malassezia sp., or other members of the transient flora, some researchers speculate that that microbial toxins or antigens could be involved in the generation of the inflammatory response. The production of porphyrins (any of various organic compounds containing four pyrrole rings, occurring universally in protoplasm, and functioning as a metal-binding cofactor in hemoglobin) by Propionibacterium sp. in the pilosebaceous duct of 58 percent of androgenetic alopecia patients (compared with 12 percent of control subjects) has also been considered to be a possible cofactor of this initial pro-inflammatory stress.

Alternatively, keratinocytes themselves may respond to chemical stress from irritants, pollutants, and UV irradiation, by producing radical oxygen species and nitric oxide, and by releasing intracellularly stored IL-1a. This pro-inflammatory cytokine by itself has been shown to inhibit the growth of isolated hair follicles in culture. Skin keratinocytes, which may also have antigen-presenting capabilities, could theoretically induce T-cell (white blood cell) proliferation in response to bacterial antigens. These antigens, once they have been “taggedâ€, are then selectively destroyed by infiltrating macrophages (cells that act as scavengers within the body), Langerhans cells (dendritic cells in the skin that pick up an antigen and transport it to the lymph nodes), or natural killer cells (immune system cells that destroy foreign bodies or abnormal cells that are marked with antibodies).

When any of the causal agents described above persist, it leads to sustained inflammation of the hair follicle. This phase of inflammation often results in tissue remodeling, where collagenases (various enzymes that catalyze the hydrolysis of collagen and gelatin) may play an active role. Collagenases are suspected to contribute to the tissue changes and the so-called “perifollicular fibrosis†by “preparing†tissue matrix and basal membranes for macrophages and T-cell adhesion.

Relations between inflammation and steroidogenesis

It has been proven beyond doubt that androgens, in the form of testosterone or its metabolites, are the prerequisites for development of common male pattern baldness. According to Mahe, the only apparent link that can be established between androgen metabolism and the complex inflammatory process proposed by him is sebum production, which is controlled by androgens. As sebum harbors a large amount of microorganisms, which use lipids as nutrients, it is possible that, at least for some individuals, androgen metabolism might make possible the colonization of the sebaceous infundibulum and sebaceous ducts by microorganisms. These microorganisms may well be involved in the first steps of pilosebaceous unit inflammation.

Conclusion

Therefore Mahe and his team deduce that the genetic factors and androgen metabolism are only responsible for about 30 percent of the androgenetic alopecia cases, and factors which lead to the lethal damage by microinflammatory process include androgens, microbial flora, endogenous or exogenous stress, genetic imbalance, amongst others. Formation of fibrous tissue or fibroplasia of the dermal sheath, which surrounds the hair follicle, is now suspected to be a common terminal process resulting in the miniaturization. Involution of the pilosebaceous unit in this form of baldness and sustained microscopic follicular inflammation with connective tissue remodeling, eventually resulting in permanent hair loss, is considered a possible cofactor in the complex etiology of androgenetic alopecia. However, till date, the inflammatory component has not been explored in developing treatment protocols for androgenetic alopecia.

 

[armandein]

Cutaneous immunopathology of androgenetic alopecia.
Young JW, Conte ET, Leavitt ML, Nafz MA, Schroeter AL.
Source

Department of Dermatology, Grandview Hospital Medical Center, Ohio University College of Osteopathic Medicine, Dayton.
Abstract


Relations between inflammation and steroidogenesis

It has been proven beyond doubt that androgens, in the form of testosterone or its metabolites, are the prerequisites for development of common male pattern baldness. According to Mahe, the only apparent link that can be established between androgen metabolism and the complex inflammatory process proposed by him is sebum production, which is controlled by androgens. As sebum harbors a large amount of microorganisms, which use lipids as nutrients, it is possible that, at least for some individuals, androgen metabolism might make possible the colonization of the sebaceous infundibulum and sebaceous ducts by microorganisms. These microorganisms may well be involved in the first steps of pilosebaceous unit inflammation.

Thank you Armandein! :bravo:

Thank you and all people, including Bryan, for many discussions in forums. They helped me to further investigate this enormous puzzle.
OTOH much remains to be clarified, an example, What is the fate of sebum which travels to the lower part of hair follicles?

 

[freakout]

I'm glad you guys are overjoyed by squeegee's posts. Me too to some extent.

I hate to break it but sebum and immunologically related issues have nothing to do with so-called "androgenetic" factors. Immunologically related issues is only a consequence of sebum issues and/or low blood supply.

But why men only? Sebum became an issue to men because of "masculus pessima". Don't bother looking for it on the net because it's a term I invented. It translates to male lousiness.

Sebum became an issue in men when they cut they hair short and not brush them as often as women do.

THere's nothing 'androgenetic' about sebum issues.

 

[armandein]

I'm glad you guys are overjoyed by squeegee's posts. Me too to some extent.

I hate to break it but sebum and immunologically related issues have nothing to do with so-called "androgenetic" factors. Immunologically related issues is only a consequence of sebum issues and/or low blood supply.

But why men only? Sebum became an issue to men because of "masculus pessima". Don't bother looking for it on the net because it's a term I invented. It translates to male lousiness.

Sebum became an issue in men when they cut they hair short and not brush them as often as women do.

THere's nothing 'androgenetic' about sebum issues.

I agree that it is the first step in the multifactorial events, including hormones, in common hair loss

 

[squeegee]

I think inflammation is the keyword for over sebum production. (Sebum peroxidation). Free radicals cause oxidative damage to sebum, and this lowers oxygen content in sebum.

 

[Bryan]

I think inflammation is the keyword for over sebum production. (Sebum peroxidation). Free radicals cause oxidative damage to sebum, and this lowers oxygen content in sebum.

So what does that have to do with "over sebum production"?

 

[squeegee]

I think inflammation is the keyword for over sebum production. (Sebum peroxidation). Free radicals cause oxidative damage to sebum, and this lowers oxygen content in sebum.

So what does that have to do with "over sebum production"?

I will ge tback to you on it Bryan.. Was about time that you show up lol

Here is an interesting one

Poor glycaemic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus.
Maxwell SR, Thomason H, Sandler D, LeGuen C, Baxter MA, Thorpe GH, Jones AF, Barnett AH.
Source

Department of Medicine, University of Birmingham, UK.
Abstract

The diabetic patient is at significantly increased risk of developing vascular disease. Its aetiology may involve oxidative damage by free radicals and protection against such damage can be offered by radical-scavenging antioxidants. We investigated whether there was a relationship between glycaemic control as assessed by measurement of glycated haemoglobin (HbA1c) and serum antioxidant status in a population of 118 diabetic outpatients with either insulin-dependent or non-insulin-dependent diabetes. Amongst patients with non-insulin-dependent diabetes mellitus there was a significant inverse correlation between levels of glycated haemoglobin and total free radical scavenging activity (r = -0.456, P < 0.0001). This association resulted primarily because of a similar correlation with uric acid (r = -0.421, P = 0.0003). There was also a weak inverse correlation with vitamin A but no significant association with vitamin C or vitamin E levels. There were no significant associations found amongst the patients with insulin-dependent diabetes. These results indicate that poor diabetic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus. By implication improved glycaemic control may preserve serum antioxidant status in diabetes.

 

[squeegee]

I think inflammation is the keyword for over sebum production. (Sebum peroxidation). Free radicals cause oxidative damage to sebum, and this lowers oxygen content in sebum.

So what does that have to do with "over sebum production"?

Propionibacterium acnes is an anaerobic bacteria, and it thrives in low oxygen environments. Oxidation changes sebum in a way that it becomes a more suitable environment for P. Acnes bacteria. The bacteria multiply in the pores of the skin and add their own inflammatory insult on the skin..which is no good. man it is late.. ill will finish tomorrow.. I just want to start sh*t! unk:

 

[Bryan]

Propionibacterium acnes is an anaerobic bacteria, and it thrives in low oxygen environments. Oxidation changes sebum in a way that it becomes a more suitable environment for P. Acnes bacteria. The bacteria multiply in the pores of the skin and add their own inflammatory insult on the skin..which is no good.

I don't doubt that that's the case, but I still don't know why that would have any effect on sebum levels.

 

[freakout]

What do you think androgens effect directly that effects the hair follicles (indirectly) on the scalp?

An Androgenetic Alopecia proponent will kill you for asking that question. And Mercado's publisher hunt me down if I post contents of his book. I know of one incident already.

But there is something that you found out by yourself that surprised me. The study can provide some insight for your thoughts which you yourself posted this on another thread before:
http://www.ncbi.nlm.nih.gov/pubmed/21271819

This may explain brain fog side effect of finasteride. Androgens are involved in blood pressure regulation. Note the mention of the nervous system on this study and the Table of Contents of Mercado's book "Neurophysiologic Mechanisms", which is actually written inside the book as 'Inheritable Neurophysiological Adaptation'. This adaptation occurs during puberty due to conditions IN SCHOOLS "Compromised Pubertal Development" (also in the Table of Contents and causes the following to become endemic in balding men:

http://www.ncbi.nlm.nih.gov/pubmed/8628793
http://www.ncbi.nlm.nih.gov/pubmed/2715645

What do androgens do? They merely tip them over to ischemic levels!!! :woot: But even with that suggestion, you'll encounter paradoxes along the way.

The HOW the the WHY is in Mercado's book. And if there anything who can explain the formation of horseshoe shape pattern, it's in there.

 

[optimus prime]

Seems a bit odd that you would plug his book.

There is no law about talking about a theory in your own words, as long as you do not copy and paste.

Why don't you do that instead?

 

[freakout]

There is no law about talking about a theory in your own words, as long as you do not copy and paste.

Why don't you do that instead?

I just presented parts of his theory/ :dunno: But if you're asking that I present the manner by which he arrived at his theory, that's a different story because it's really a long long long explanation involving several factors linked together. It's also unique.

Legal doesn't mean it's moral. No writer is comfortable with existing copyright laws.

 

[optimus prime]

I just presented parts of his theory/ But if you're asking that I present the manner by which he arrived at his theory, that's a different story because it's really a long long long explanation involving several factors linked together. It's also unique.

Legal doesn't mean it's moral. No writer is comfortable with existing copyright laws.

ok, but I disagree.



Anyway. Do you think blood viscosity is a factor. For example in many hot countries where blood is thinner they don't seem to have as much hair loss. Also genetics, different blood types have different viscosity.

I still believe DHT plays a direct role, but do you think the thickness of blood matters?

For example, when I go to the Philippines I always feel my hair gets better, but my blood thins a lot when there. (hotter climate so body thins blood to cool down, also I drink WAY more water).