Understanding Androgenetic Alopecia

[Armando Jose]

Thanks. Does sebum flow downwards too then? Or only upwards? What do the studies say about that?

http://bsapp.com/forensics_illustra...s_of_Hairs/Pulled_out_hairs_multiple_x100.jpg

Can you see sebum at the bottom of hair?
This photo is dyed with osmium tetraoxide, (fats and sebum get a intense black colour), not with the usual eosin.... where fats are eliminated before.....

another proof that the sebum reaches lower part of the hair (dermal papilla) arein certains cases with sebohorera, concretions found when the hair is pulled.

The most logical is that once sebum leaves the sebaceous gland is that it scatters in all directions

Studies of penetration of drugs (Berlin Lademann) through the hair follicle show that there is a current flowing into the lower part.

- - - Updated - - -

And what do you exactly mean by "became convinced that if hormones are involved, it is not what defines a person to stay bald and some not"? Genetics eventually determine that right Armando? Or do you think otherwise?

Genetics give us the type, density etc of our hair, but I dont think in baldness gene...

 

[stressftw]

http://bsapp.com/forensics_illustra...s_of_Hairs/Pulled_out_hairs_multiple_x100.jpg

Can you see sebum at the bottom of hair?
This photo is dyed with osmium tetraoxide, (fats and sebum get a intense black colour), not with the usual eosin.... where fats are eliminated before.....

another proof that the sebum reaches lower part of the hair (dermal papilla) arein certains cases with sebohorera, concretions found when the hair is pulled.

The most logical is that once sebum leaves the sebaceous gland is that it scatters in all directions

Studies of penetration of drugs (Berlin Lademann) through the hair follicle show that there is a current flowing into the lower part.

- - - Updated - - -



Genetics give us the type, density etc of our hair, but I dont think in baldness gene...

Armando i saw alot of posts of you regarding the sebum related to the male pattern baldness, what do you think about accutane?
we all know accutane is related to hairloss but certainly not male pattern baldness, could accutane have positive impact on male pattern baldness?
as far as i know its the only drug capable of reduce sebum in a very high scale permanently
there is some studies showing that accutane has a effect of lowering the DHT through inhibition of of the 5-alpha reductase type-1 enzyme too.

Link of these studies:

http://www.sciencedirect.com/science/article/pii/S0303720706005624

http://www.pnas.org/content/96/23/13512.full.pdf


http://www.sciencedirect.com/science/article/pii/S0006291X03003322

- - - Updated - - -

"13-cis-Retinoic acid competitively inhibits 3a-hydroxysteroid oxidation by retinol dehydrogenase RoDH-4: a mechanism for its anti-androgenic effects in sebaceous glands?"




"Retinol dehydrogenase-4 (RoDH-4) converts retinol and 13-cis-retinol to corresponding aldehydes in human liver and skin in the presence of NAD+. RoDH-4 also converts 3a-androstanediol and androsterone into dihydrotestosterone and androstanedione, which may stimulate sebum secretion. This oxidative 3a-hydroxysteroid dehydrogenase (3a-HSD) activity of RoDH-4 is competitively inhibited by retinol and 13-cis-retinol. Here, we further examine the substrate specificity of RoDH-4 and the inhibition of its 3a-HSD activity by retinoids. Recombinant RoDH-4 oxidized 3,4-didehydroretinol—a major form of vitamin A in the skin—to its corresponding aldehyde. 13-cis-retinoic acid (isotretinoin), 3,4-didehydroretinoic acid, and 3,4-didehydroretinol, but not all-trans-retinoic acid or the synthetic retinoids acitretin and adapalene, were potent competitive inhibitors of the oxidative 3a-HSD activity of RoDH-4, i.e., reduced the formation of dihydrotestosterone and androstandione in vitro. Extrapolated to the in vivo situation, this effect might explain the unique sebosuppressive effect of isotretinoin when treating acne."

 

[Swoop]

I think my SHBG is more low because of my genetics. I can't do that much about it. I didn't measure my blood levels more often though.. Will do that this year. If your SHBG is low because of insulin resistance or metabolic syndrome or something else it's way easier to fix I guess. Exercise, green tea, soy intake are some things that have shown to increase SHBG levels. I raise big question marks about how much you can influence SHBG especially if you are healthy otherwise, seems almost impossible from what I have read. If someone has input for me then that would be great.

I have always thought a good approach would be to clone a person's hair follicles, grow those under laboratory conditions, and then transplant. What are alternate approaches using regenerative/gene therapy? How far away do you think those are?

Thanks for posting your SHBG and free testosterone numbers. That was interesting to compare against my own. FYI: a better marker for free testosterone is what is known as "free and weakly bound testosterone". This uses a more accurate chemistry and includes the fraction bound to albumin, which is actually bioavailable. This type is known as "bioavailable testosterone" as well. "Free testosterone can underestimate the actual amount significantly.

Indeed you are right about the testosterone, thank you. In terms of regenerative therapy I was indeed aiming to clone hair follicles. Some exciting teams that are working on this research are;

- Takashi Tsuji (Tokyo)
- Lauster et al. (Berlin)
- Jahoda et al. (UK/USA it seems)

Regenerative therapy would be great for a "full cure" as I would like to call it. It would give the possibility to get your full head of hair back. How far do I think these technologies are? Not close enough that's for sure. Nobody worldwide is even initiating pre-clinical trials yet. As you can imagine everything takes much time so even if they would have the "eureka" moment tomorrow it would still have to go through all the clinical trials. And remember that is only if everything goes well. What if they stumble upon problems? So, yeah you get the point.. A commercial venture that gets on the market in the near future is a fantasy. Exciting research? Yes, but certainly too far away at the moment.

In terms of gene therapy I don't see that quick how that could apply to a "full cure". However in terms of a "functional cure", that means as a full on preventative treatment, it could be quite exciting yes. Remember we actually do know how to stop Androgenetic Alopecia completely. All you would have to do for example is silence the androgen receptor completely and Androgenetic Alopecia would never set in or proceed. The pathway chain would be completely broken. For someone who hasn't started balding yet or is in the early stages of balding, that would be basically everything he needs. Someone who is NW6 won't get his hair back with that. For example it could be perhaps possible to induce a AAV-shRNA (http://www.ncbi.nlm.nih.gov/pubmed/19642108) to the scalp to silence the androgen receptor.

That would mean hypothetically that you would be immunized to Androgenetic Alopecia for a long amount of time, with no side effects at all. I could make a post about that in the future. It's quite realistic to envision something like that actually. Although I haven't read that much about it yet. Imagine the "ethical questions" gene therapy for Androgenetic Alopecia would bring though... Yeah that would be something :laugh:.

- - - Updated - - -

Yeah its kind of funny the stuff James B. Hamilton did that long ago is still to this day the only proven way we know of for sure to actually stop male pattern baldness.
Swoop you use RU and finasteride then right. What do you think of the safety long term of these 5-ar inhibitors? I get a little worried it inhibits 5-ar 3 , crosses blood brain barrier, and might affect neurotransmitters. That is my biggest worry along with any possible prostate cancer effect. Mainly why I have never tried it, and my male pattern baldness is very very slow so im not in dire straights.
Your opinion I guess is use an AA right away.

abcdefg,

Yeah funny huh.. I bet that almost nobody has read these papers honestly . It's from year 1942: "Male hormone stimulation is prerequisite and an incitant in common baldness".

I cycle RU/finasteride now with an off period. I don't use them together that would be too harsh of a combination for me.

My opinion isn't exactly to use an AA right away. Actually anno 2016 we have sub-par treatments in my opinion and we are severely limited.

But yeah if you remember that;

- Androgenetic Alopecia seems to be extremely complex
- We have little researchers worldwide focussing on the problem, very little actually.
- No proper models (rodent model)
- Red tape that slows everything down significantly.
- No recognition for Androgenetic Alopecia

Put all those factors together and one can understand why advancements are SLOW AS HELL. Hellouser explained this in a topic recently.

I often say prevention is extremely important because Androgenetic Alopecia seems extremely hard to reverse. I think many people don't seem to grasp that. If you neglect the current options we have because you hope for a possible reversal "cure" in the near future then you are walking in the clouds. Sure a miracle may always arise, but what are the odds of that to happen? Almost non-existent. It's that simple. Instead of a reversal cure we have more chances of perhaps some sort of better maintenance treatment in the near future. That's way more likely in my opinion.

You should research the current options and weight the risk/benefit for yourself. It's really a personal decision to be honest abcdefg. Finasteride sides are definitely real, and I believe they hit more people than the clinical trials say they do. That being said we don't have much to work with really. Personally I feel that finasteride is definately worth a try. The majority of people seem to do completely fine. Although there are certainly people that can't handle the stuff. Well you can always quit.. These lingering side effects are concerning in a very small subset of people but even most of those people seem to recover eventually. Again risk/benefit man..

I wouldn't be worried at all about prostate cancer risk personally. And in regards to brain function, you will probably feel it mentally if you don't react well to finasteride. Again you could quit and in almost all cases be perfectly fine.

I get subtle but unpleasant sexual side effects on finasteride though. I seem to become a tad more sensitive to RU58841 too. Luckily for me I react very well to both treatments. My hair quality improves extremely well on both. I opt for a minimum maintenance treatment now. I need to, because unlike you I will lose my hair pretty rapidly if I'm not any treatments for a long duration of time.

 

[Armando Jose]

Armando i saw alot of posts of you regarding the sebum related to the male pattern baldness, what do you think about accutane?
we all know accutane is related to hairloss but certainly not male pattern baldness, could accutane have positive impact on male pattern baldness?
as far as i know its the only drug capable of reduce sebum in a very high scale permanently
there is some studies showing that accutane has a effect of lowering the DHT through inhibition of of the 5-alpha reductase type-1 enzyme too.

Most of people using accutane to treat acne have problems with hairloss.

In my theory sebum is a key in the process, but the real problem is not the quantity but quality. Sebum in my opinion is vital for a healthy hair growth, the problems arrive when the sebum flow is deteriorated.

 

[stressftw]

Most of people using accutane to treat acne have problems with hairloss.

In my theory sebum is a key in the process, but the real problem is not the quantity but quality. Sebum in my opinion is vital for a healthy hair growth, the problems arrive when the sebum flow is deteriorated.

i do agree with you in some parts, i do think sebum can have a important role in Androgenetic Alopecia but regarding the hairloss due to accutane im certain that there its nothing about Androgenetic Alopecia and its temporary hairloss in most of cases(telogen effluvium)
accutane was used previously as a chemotherapy for treating various different types of cancers as far as we know chemotherapy drugs most known side effect is hair loss, accutane can cause a permanent hair loss like chemotherapy drugs that is called chemo perm.
also accutane can permanently modify the genes and its play a role on these genes

Oxyticine......................................reproduction
Growth hormone...........................Growth
Phosphoenol puryvate...................Gluconeogenese (metabolism of sugar)
Alcohol dehydrogenase..................alcoholic oxidation
Transglutaminase..........................Growth and death of the cells
Laminine B1..................................Cellular interaction
GLA matrix protein.........................Growth and synthesis of the bones
Keratin..........................................Skin
Retinol binding protein type I...........Vitamin A metabolism
RAR............................................... Vitaminic A action
HOX 1.6..........................................fœtus growth
Dopamine receptor D2.....................CNS (central nervous system).

acne, and sebum problem is related to the KERATIN so to fix the problem accutane acs on the keratin gene and it changes the way it replicates. thats why people get dry everywhere when take the drug and be acne free and also for long term accutane leaves traces of retinoic acid in cell receptors and thats the reason some people never get the oily skin back again.

Once Accutane is introduced in the body, damage is starting to be done to the body. Cells dies at a greater rate or grow at an anarchic rate(chemotherapy effect). Most of the people can repair the damage so the rate at which cells are repaired is greater than the rate at which cells are damaged. Remember that each day millions of cells are created and millions of cells are dying. It is the aging process. Accutane in some person illicit a greater damage rate and the body with time is no longer able to repair the damage at the same rate it is done. Thats why some people have reported side effects from Accutane years after they stopped the drug.
Once you have taken accutane the way your DNA is transcripted and replicated is modified, it just like you are genetically modified.

whats the paper of the keratin on hair? whats the correlation with Androgenetic Alopecia? somehow i think accutane can have positive or negative impact on Androgenetic Alopecia this drug is one of the most powerful and complex drugs ive ever seen

 

[Swoop]

Came to my attention that Walker made this thread; http://www.hairlosstalk.com/interac...to-hair-loss?p=1294380&viewfull=1#post1294380

Directs to this link; http://science.sciencemag.org/content/351/6273/aad4395#corresp-1.

While this is a mouse model and unrelated to Androgenetic Alopecia the picture from there fits well "overall" into this thread and the implications I describe here;

Androgenetic Alopecia might be simply in a "sense" premature aging of the hair follicle, due to some form of damage as I already described (DNA damage, ROS or other forms of damage/stress).

AR gene seems to play a very central role.

I can also understand in a broad sense why 17b-estradiol is so good at regrowing hair in combination with heavy anti-androgen therapy in relation to all of this. Especially, when we take a look at some of the primary downstream pathways of 17b-estradiol.

It's all hypothetical obviously, but nonetheless very interesting.

 

[drgs_not_hugs]

SHBG is a buffer for testosterone. Testicles cannot produce large amounts of testosterone in seconds on command, so the body saves it up.
Testosterone is then released in spikes when needed. This is basically what bound T is for.

What are these moments of spiking T:

Compound strength training, squats and dead-lifts give a major surge in free T during the exercise, but SHBG increases the following days. Basically you've freed a big portion of T, and need to build it up again.

Sex and all types of arousal, same here.

Social stress. A person who has accepted his low social status has low testosterone. A person who has low social status and is worried about it/is climbing, has high T.
A person who has high social status and does not worry about losing it, has low T. A person who has high social status and is worried about it/is falling, has high T.

Etc

 

[Armando Jose]

Thank you for the study Swoop, it is very interesting, and seems that all the new investigations point out to the areas near dermal papilla ,,,, as S Foote and me think

"In androgenetic alopecia, hair fibers become
shorter, thinner, and fewer as thick
terminal scalp hairs are gradually replaced
by fine vellus hairs. Yet in the early stages of
this condition, HFSCs appear generally normal;
a failure in their activation to form hair
germ cells was the problem (11). Hair germ
arises from activated HFSCs and migrate out
of the bulge during early catagen to support
the generation of a new hair. This suggests
that the environment affects HFSCs."