NLRP3 Inflammasome Cause Of Male Pattern Baldness

[LeeLemonoil]

Inflammasome is not causing it, it is there to try prevent it getting worse. The cause is fascial tension, causing stress on the tissue (scalp, joint). If you want to stop chasing the effect and start looking at the cause you can find much in my post history.

DHT is one of the primary hormones that maintain fascial tension instead of giving in to the stress.

That’s sophism. Overactive Nlrp3 is here a cornerstone of a theory. Of course these inflammasomes exist to react to stress and are there to help eliminate stressors. But that’s not how physiology work and certainly not how interventions work. According to our theory here hairloss is both the result and necessary part of the Stress response. Whatever root cause the Stress has. What is the reason to your claimed cause facial tension? Where does the causal chain begin that leads to facial tension -> hairloss.

And the DHT bit is interesting and why not? In physiology, most thinks have various effects and interconnected roles. DHT might indeed lead to a personality/behavior that faces stress with rigidness and tension. Both locally and systemically. Don’t you think that DHT-caused fibrosis is not also a reason for tension? Fibrotic tissue is very tense and rigid. Certain DHT-signaling might be both cause and consequence of tension. A Self-reinforcing downward spiral. As is often the case in physiology again.

 

[MitchMitchell]

some more thoughts:

things like exercise


with all due respect, nonsense.

The brilliant minds on this forum along with Ray Peat himself and all the other great online biologists and anecdotes we have access to, there is no reason we cannot cure MPB.

(the only reason i could imagine would be that (God forbid) merck / pharma companies zucc the thread, which is why i suggest we start archiving this info lol)

the pain of premature hair loss (which we can all see is occurring faster and younger in this modern age) + being told by the media that the only solution is chemical castration, brain damage or expensive surgery and that purely having androgens is the reason they should suffer is enough to induce the masses to the openness required to consider the possibility of metabolic disorder / chronic inflammation being a causing factor in many illnesses (not only MPB).

the same learned helplessness crowd on r/tressless who cling to scientism mythology of "the big 3 and dht sensitivity (lmfao)" and mock alternative theories are the same people who also all gradually break down and rant that "its ridiculous and insane that we have rovers on mars / ai etc but not a reasonable cure for baldness". They don't even realise how badly they want this awakening on the parasitical pharmaceutical industry to occur.

I kinda skimmed through your post because it seems that you ran with the idea that I said that hair loss is impossible to prevent. I was saying that cheap solutions such as the ones I mentioned will never be pushed forward and recommended in guidelines.

It’s not about learned helplessness it’s about knowing how things work. Don’t assume everyone is a wimp.

 

[rei]

That’s sophism. Overactive Nlrp3 is here a cornerstone of a theory. Of course these inflammasomes exist to react to stress and are there to help eliminate stressors. But that’s not how physiology work and certainly not how interventions work. According to our theory here hairloss is both the result and necessary part of the Stress response. Whatever root cause the Stress has. What is the reason to your claimed cause facial tension? Where does the causal chain begin that leads to facial tension -> hairloss.

And the DHT bit is interesting and why not? In physiology, most thinks have various effects and interconnected roles. DHT might indeed lead to a personality/behavior that faces stress with rigidness and tension. Both locally and systemically. Don’t you think that DHT-caused fibrosis is not also a reason for tension? Fibrotic tissue is very tense and rigid. Certain DHT-signaling might be both cause and consequence of tension. A Self-reinforcing downward spiral. As is often the case in physiology again.

sophism? GTFO.

Chronic postural damage and injury are the foremost reasons for fascial tension. In today's world a vast vast majority of people have ingrained chronic postural damage. You don't fix this by taking castration drugs, you fix it by "physiotherapy" or what i have called chiropractic yoga when i have performed it. On youtube it seems to be called myofascial unwinding.

Thousands of years ago already yogic teachings stressed that the cornerstone of health is to have a straight spine. Most of today's people are unable to achieve a straight spine even when using effort, let alone it being their neutral posture. Even medical establishment has normalized this S-spine when 100 years ago they still knew the J-spine is what is normal.

 

[Kenny]

sophism? GTFO.

Chronic postural damage and injury are the foremost reasons for fascial tension. In today's world a vast vast majority of people have ingrained chronic postural damage. You don't fix this by taking castration drugs, you fix it by "physiotherapy" or what i have called chiropractic yoga when i have performed it. On youtube it seems to be called myofascial unwinding.

Thousands of years ago already yogic teachings stressed that the cornerstone of health is to have a straight spine. Most of today's people are unable to achieve a straight spine even when using effort, let alone it being their neutral posture. Even medical establishment has normalized this S-spine when 100 years ago they still knew the J-spine is what is normal.

making your beard grow less course is not the same as mending male pattern baldness. If you had some actual proof of scalp hair regrowth you would be taken seriously.

don’t tell high quality posters to leave.

 

[GorillaHead]

Inflammasome is not causing it, it is there to try prevent it getting worse. The cause is fascial tension, causing stress on the tissue (scalp, joint). If you want to stop chasing the effect and start looking at the cause you can find much in my post history.

DHT is one of the primary hormones that maintain fascial tension instead of giving in to the stress.

You realize it cant be tension. Studies have shown that hair follicles increase in thickness under tension. In fact the body adapt to tension well. If tension had anything to do with it. Then babies would not be getting thicker hair as they grow.

the body adapts to tension.
Skin stretches when it needs to. Bone will also remodel. Dht drops off as we get older. The galea can grow under tension. So do follicles.

i am sorry but this theory is one that has zero studies backing it. None of us are gonna spend time following whats likely to be a dead end especially since there is data in other places painting a much clearwr picture.

 

[rei]

Not only less coarse, but also fill in and become more dense, or less uneven is better description, pretty analogous to certain kind of baldness even if not MPB

Rude and insulting people can go to hell. Why is it so hard to have a civilized conversation even if you happen to disagree with the argument?

GorillaHead: you are entitled to your opinion. I'm just sharing a general picture i have come to know, you may wait until it is presented in medical literature after a decade. I could tell you about 10 other chronic conditions caused by fascial tension that currently have no explanation, but that would be offtopic.

 

[MitchMitchell]

This forum doesn’t like that the only people with massive regrowth all pop a lot of anti androgens + estradiol. Oftentimes with very limited side effects.

It must be something else at work

 

[Kenny]

Rude and insulting people can go to hell. Why is it so hard to have a civilized conversation even if you happen to disagree with the argument?

GorillaHead: you are entitled to your opinion. I'm just sharing a general picture i have come to know, you may wait until it is presented in medical literature after a decade.

There were literally no insults thrown at you.

 

[rob]

“Stimulation of the immune system in hyperthyroid rats revealed that monocyte migration and ROS production by macrophages were suppressed. In contrast, hypothyroidism enhanced ROS release, whereas monocyte migration was not affected (64).”


This is huge as most people who are hyperthyroid do not lose their hair.

the genes that what were found to be related to AGA besides AR were related to HdAc4 and HdAc9. Hdac9 related to macrophages and lack of cholesterol efflux

Interesting to hear that HDAC9 is involved in cholesterol efflux given previous discussions. As per HDAC9 represses cholesterol efflux and generation of alternatively activated macrophages in atherosclerosis development seems to undermine ABCA1, ABCG1, and PPAR-γ signalling in macrophages (so FA and cholesterol accumulation) which, understandably, goes in parallel with M1 polarization.

Don't know whether with this level of repression whether related nuclear receptor ligands are going to be particularly efficacious, even at higher doses. Haven't looked into it on the hair front specifically but maybe there are other epigenetic marks we can promote that would be helpful? The ascorbate and AKG dependent JMJD3/TET demethylation marks jump to mind as maybe helping de-repress silenced genes and JMJD3 seems particularly important in M2 polarization.

Know we've discussed class IIa HDACs a lot before and I guess the same practical issues are present i.e. how to selectively inhibit them. There's a lot of research that needs to be done on elucidating HDACi effects of various natural substances. It's certainly an active area of drug research.

 

[rei]

There were literally no insults thrown at you.

you need to learn what sophism means

 

[Kenny]

This forum doesn’t like that the only people with massive regrowth all pop a lot of anti androgens + estradiol. Oftentimes with very limited side effects.

It must be something else at work

Popping estradiol with limited side effects? Lol? By popping I hope you mean applied in small doses topically or not at all. Estriol might have fewer sides, estradiol with give you breast tissue.

anti androgens have side effects. You are correct in that they are not guaranteed.

 

[Kenny]

you need to learn what sophism means

It meant your argument was false. it is literally the opposite of ad hominem.

this is not worth thinking about

 

[MitchMitchell]

You don’t have the clinical experience with regards to estradiol so your opinion / sarcasm is pointless.

 

[MitchMitchell]

Estriol is pointless. Estradiol is great. Other estrogens should be avoided. Same with progesterone vs synthetic progestins.

Listen to Neal Rouzier if you want to educate yourself on test, e2, etc.

 

[GorillaHead]

Popping estradiol with limited side effects? Lol? By popping I hope you mean applied in small doses topically or not at all. Estriol might have fewer sides, estradiol with give you breast tissue.

anti androgens have side effects. You are correct in that they are not guaranteed.

Finasteride did not thing for my hair. Zero benefits. Only negatives. I tried it for a year.

 

[rei]

It meant your argument was false. it is literally the opposite of ad hominem.

this is not worth thinking about

A sophism, or sophistry, is a fallacious argument, especially one used deliberately to deceive.

That's about as insulting as it gets, i try to do the exact opposite, share what i have come to know. I may be wrong but i certainly don't try to argue fallaciously or deceptively.

 

[MitchMitchell]

Just a quick read for those of you here who still think that all estrogens are the same biochemically, which makes about as much sense as saying that all dogs behave the same because they’re, ugh, “dogs”

https://watermark.silverchair.com/j...dVHYePpBwK1bUDRheLEvrzYrOQVc7olly-JiQxIhy7MP-

 

[rei]

You realize it cant be tension. Studies have shown that hair follicles increase in thickness under tension. In fact the body adapt to tension well. If tension had anything to do with it. Then babies would not be getting thicker hair as they grow.

the body adapts to tension.
Skin stretches when it needs to. Bone will also remodel. Dht drops off as we get older. The galea can grow under tension. So do follicles.

i am sorry but this theory is one that has zero studies backing it. None of us are gonna spend time following whats likely to be a dead end especially since there is data in other places painting a much clearwr picture.

Yes, DHT causes increased hair growth and thickening of hair. Don't you see how this increases metabolic demand? When fascial tension limits nutrient transport and circulation the follicle suffers. Reducing the follicle's metabolic demand through removing DHT may allow it to work normally for a short time even if we don't consider the reduction of tension the removal of DHT causes in the fascia. But this is only a temporary "fix". The root cause is still there.

 

[Kenny]

@Ableton sent me this recently, I think its extremely relevant to this thread.


Oral Steroid Made My Hair Grow Back Thicker!

The relevant information is in the quote below

Oral Steroid Made My Hair Grow Back Thicker!


OP:

„Hey everybody, first time poster here.

Felt the need to share this in the hope that somebody will give me an explanation.
There's a lot more to this story but I'll make it brief and straight to the point.

For the past 7 weeks I've been taking an oral steroid called Anavar (Oxandrolone)
Over this time I have noticed my hair has got much thicker all over, which is bizarre to me because I'm prone to male pattern baldness and was fully expecting this cycle to make me lose the last of my hair. What's going on?? I could genuinely feel my hair growing and it was never itchy like before.

My cycle finished yesterday and already my hairs texture is starting to change back. It feels like it was before, much thinner and fuzzy. This really pisses me off because I was starting to remember how awesome it was having hair haha.

If anybody has any questions feel free to ask, as I said there is much more to this story but not sure if I'm just talking to myself on here!

Cheers“



All of Chemheads responses (I bolded some stuff, his first post is probably the most uninteresting one so do not get discouraged too quickly)



„Not sure if you still browse the forums, but I could probably help you figure out why your hair got thicker if you can provide a little more information.

What dosage were you taking and for how how long? How long did it take for you to notice the increase in thickness and, after discontinuation, how long did it take for you to notice diminishing of the thickness (you kind of already answered this one)? Did you notice any other side effects, whether perceived positive or negative - increase in beard or body hair thickness, change in pigment of hair (darkening), increase in skin oiliness or dryness, increase in skin redness or irritation?

There are a number of possibilities I suspect and I'll go over one... Since oxandrolone is not metabolized by 3-beta or 3-alpha HSD, it remains an active androgen until it's probably glucuronidated for elimination from the body. Despite what you hear from mainstream science about androgens and hairloss, testosterone does not cause hair loss. Every steroid has the ability to invoke a unique genetic expression when bound to its respective receptor and their physiological effects should never be classified by their affinities for those receptors (i.e. DHT causes more hair loss than testosterone because it's bound with higher affinity than testosterone). Testosterone and DHT invoke their own unique gene expressions when bound by the androgen receptor.

It could be that the relative binding affinity for oxandrolone (anavar) may be similar or even higher than DHT, which means that it's possible that it binds the androgen receptor with high affinity and can continue binding without metabolism by 3-b,a HSD. This keeps DHT from binding and expressing the genes that cause hair loss without disrupting a whole lot with respect to hypothalamic regulation of steroid production and metabolism. Since oxandrolone is not DHT, binding the androgen receptor doesn't cause expression of the genes that cause hairloss... because again, each steroid invokes a unique genetic expression when bound by a receptor or response element.

In a sense, oxandrolone could be acting as an androgen receptor antagonist, but only as an antagonist with respect to gene expression which negatively affects hair. In every other sense, it invokes genetic expression that promotes the positive effects we need from androgens... it's not impotent like an androgen receptor antagonist would normally be. Since it's non-aromatizable, you don't end up with excessive estrogenism and ultimately negative HTPA feedback. This is also important because negative HTPA feedback will ultimately cause you to produce less steroids and, depending on the type of feedback, alter steroid metabolizing enzyme expression. If you have higher steroid production, you'll have higher levels of whatever steroid is responsible for thickening of the hair and when you throw oxandrolone into the mix, you're reducing the binding of steroids that negatively impact hair growth (DHT) by giving the androgen receptors something else to bind.“



„I'll also add that if you look at the conformations of testosterone, dihydrotestosterone, and oxandrolone, side by side, you can see that oxandrolone is structurally similar in conformation to testosterone. In fact, due to the resonance structure of the lactone in the A ring of oxandrolone, it's even flatter in conformation than testosterone when comparing both to DHT, which makes me suspect that may be the reason for oxandrolone's similarity to testosterone with respect to gene expression, while simultaneously being already 5-alpha reduced and non-aromatizable.“



reyl said:

So what would happen if someone ran finasteride or dutasteride while also taking Anavar?

“Finasteride and Dutasteride are a slippery slope. They can work well for some people and not so much for others and a lot of it is dependent on the extent to which 5-alpha reductase is expressed in different tissues. The most ideal case for use of finasteride/dutasteride would be someone whose expression of 5AR is already low or unaffected by 5AR inhibitors in tissues that we don't want affected. The reason is that 5AR inhibitors cause hypothalamic suppression of steroid synthesis and alter steroid metabolizing enzyme expression (not the obvious change in 5AR, but also aromatase and possibly the different types of hydroxysteroid dehydrogenase enzymes). Most people that take 5AR inhibitors are very likely androgen deficient, but fooled by testosterone levels from blood work. If you take finasteride and your testosterone levels are higher than before, that only says something about the concentration of testosterone in serum. It does NOT reveal anything about total androgen synthesis or even total steroid throughput in the body, because steroids are metabolized once they reach different tissues. By taking finasteride, you're actually decreasing total steroid throughput... the natural process would be for testosterone to reach target tissue and be metabolized. Some is 5 alpha reduced, some is aromatized, and some is bound by receptors as-is. Cutting off that metabolic pathway (5AR) increases testosterone concentration and, subsequently, concentration of estrogens, but only for a short time due to negative hypothalamic feedback. You actually want DHT, especially in the brain, because it allows your body to produce higher levels of steroids, including estrogens. Cutting off 5AR results in higher serum levels of testosterone and estrogens, but LOWER levels of estrogens in the tissues where they belong. Estrogens don't belong in serum. They should be created in the tissue where they're needed and then rendered inactive before they end up back in serum for elimination. This way, you end up with higher steroid production and throughput and, thus, higher levels of the steroids which are good for hair. In an ideal world, we would probably want high expression of 5AR in sexual tissues and the brain and lower expression in the skin and hair. This would ensure high steroid production and throughput, but low metabolism of testosterone to DHT in hair follicles. This localizes the effects of estrogens to the hair follicles without raising the serum concentration of estrogens.

So, to answer your question, for people taking finasteride, adding anavar will likely do nothing to help and may possibly hurt due to hypothalamic suppression. If anavar is taken on its own, though, it's possible you may be able to eliminate most of the negative physiological effects of DHT binding the androgen receptor without also causing a rise in serum estrogens (thus keeping autocrine production of estrogens in the hair follicle higher). That's ultimately what we want. We want to eliminate the negative effects of DHT in a way that doesn't lead to negative hypothalamic regulation so we can keep all our other steroid activity as it normally is.

I will tell you this... the only way that finasteride works for me is if I take a high dose (5-10mg) daily, causing a sharp, quick decrease DHT and increase in estrogens. The increase in estrogens lasts for a very short period of time and I have incredibly thick, dark hair for maybe 3-5 days.. thicker than when I was a pre-pubescent kid. After that, my hair becomes thin, dry, and sheds like it would if I hadn't taken finasteride (possibly even worse). Keep in mind, this is with extremely low levels of DHT, so the lack of presence of DHT isn't the whole picture like many might think. male pattern baldness is not entirely linked to androgens.. it's also very closely interwoven with the lack of presence of other steroids. This also links female and male pattern baldness... two different sides of the same coin in a way, I guess.”


Matt Rogers said:

10 mg of finasteride? That's insanity lol

“It is insanity. And because of my experiences with finasteride, I don't believe DHT really has a very strong role in hair loss. The scalp doesn't have the right environment to grow hair properly because there is a deficiency in "something" that is temporarily increased due to the inhibition of 5 alpha reductase. That could be an estrogen, a mineralocorticoid, a glucocorticoid... These are all options. I know for certain that if DHT were the problem, then my hair would be amazingly thick and stay that way with finasteride. It doesn't, though. It reaches a peak after about 3 weeks and then becomes thin and sheds again after whatever increased is downregulated. Many hair loss sufferers could possibly be suffering from a low grade, undiagnosed form of adrenal hyperplasia due to an enzyme malfunction or deficiency.”



Matt Rogers said:

I'm in the same boat as you. I've been taking 1mg for about 4 months now. I started as a firm norwood 1.5 now im a norwood 2+ It has made my hair loss way worse. I regret taking it and miss my old hair pre finasteride. I'm hoping to quit soon and hopefully quitting will result in some kind of regrowth, but that is a longshot

“The effect that I could get with finasteride was actually really quite amazing, but I had to take high doses for a short period of time. After about 3 weeks, the hypothalamus and pituitary would adjust my steroid production and all the positive effects would disappear. My hair is naturally extremely fine and it always has been since childhood. Finasteride would make my hair extremely thick, dark, and heavy... And by thick, I mean the hairshaft diameter was like double the size at least. It also made the hair on my body thicker and darker, and made my skin look amazing. So, finasteride's mechanism in terms of hair growth has nothing to do with decreasing DHT... It's about what steroids increase as a result of cutting off the 5 alpha reductase pathway. Imagine creating a dam and blocking the flow of a river.. It backs up and increases the flow of that water to other little rivines and areas. I thought at one point that an increase in estrogens might be responsible since cutting off 5 alpha reductase would increase testosterone concentration and, thus, estradiol. To test this, I took finasteride and after it's positive effects went away a few weeks later, I injected testosterone. I got all of the effects of high estradiol, but absolutely no increase in hair thickness or anything positive. It was actually horrible lol.. I felt like death. So, I know that some steroid must increase as a result of taking a 5 alpha reductase inhibitor... And it doesn't seem likely that any estrogen is the one I'm looking for.. And it would also seem that it must be one that's not commonly discussed or studied in scientific publications. It's probably also not one that would be commonly tested for in a lab or used in hormone replacement therapy... Because if it were, I'm sure plenty of people would report positive changes in hair. So, I'm thinking that something like deoxycorticosterone or 11-deoxycortisol may be it. They're 5 alpha reduced steroids... So taking a 5 alpha reductase inhibitor would increase their concentrations.. Temporarily until the hypothalamus and pituitary down regulate total steroid production.”





Matt Rogers said:

Wow your knowledge about this stuff is incredible. Do you have any suggestions for me since finasteride isn't working. My hair used to be pubic-like thick and dark. And now it is dry, finer and straighter and falls out like crazy. Also my eyebrows have thinned out especially the outer part of my eyebrow. I read that eyebrow loss is usually caused by thyroid, so I'm thinking maybe finasteride could possibly be interacting with my thyroid somehow.

“So, right now, I've changed my diet and I've been following it pretty religiously for the past year. I've been able to eliminate irritation and inflammation in the scalp and my hair pretty much just doesn't fall out. I'm obviously still missing something genetically that people who don't experience hair loss do have... And whatever that is, I was kind of able to temporarily exploit it with finasteride. I have no scalp problems and any hair I do lose is very little and would be considered relatively normal. With the finasteride, for a short window, not a single hair would come out no matter how hard I tried to make it. Also, I had a ton of vellus hair that sprouted in just days in my hairline. None of that happens with this diet... But, I am slowly regaining density, my hair certainly looks and feels better, and I would expect that in another 6 months or so, no one would probably ever know I've lost hair. It will, however, still be really fine and won't look anywhere near what it did when I cycled on and off finasteride.

Anyway, my diet would be generally disgusting to most people and I'm not really doing it for the hair.. It was just something that I conveniently and happily noticed. I basically eat a totally raw food diet. I eat fruits and vegetables... Like a sickening amount lol. I believe this, in addition to the supplements I take, have helped my adrenal glands, kidneys, and thyroid function more optimally. I think my body is much less forgiving than others who can simply eat what they want and not suffer from hair loss or some other kind of disorder/disease. It's similar to people who may have rheumatoid arthritis.. There's definitely something genetically inferior about those people that makes them more susceptible to arthritic pain than other people, but many of them can get rid of their pain so that it's pretty much unnoticeable if they're saints about what they eat. Their problem is also similar to hair loss sufferers in the sense that it's probably related to some kind of enzyme inefficiency or deficiency. They probably lack enzymes in joint tissues that metabolize certain steroids to anti-inflammatory glucocorticoids.. Just like I believe we lack enzymatic expression in the skin for same kind of thing... Either some kind of glucocorticoid or mineralocorticoid.

So, I believe the diet offsets that genetic shortcoming to a degree and rids me of inflammation. But, if I figure out what steroid was temporarily increased from finasteride use and supplement with it, I will have exactly what I'm after.. And a more complete picture of what causes hairloss. I'm thinking right now that it may be related to some kind of 21-hydroxylase or possibly 11b-hydroxylase enzyme deficiency.. Especially since those things cause excessive androgen production and are also responsible for hirsutism and fine thinning hair/female pattern hair loss in women. They cause excessive androgen production obviously because if you're not making enough of a particular glucocorticoid or mineralocorticoid due to poor enzymatic metabolism, the adrenal glands must release more steroids to make up for that.. If the quality of the machinery is poor, you have to throw more material at it to have enough product. And mineralocorticoids and glucocorticoids control salt/blood pressure regulation and blood sugar regulation, respectively. Those are two incredibly important things.“





“One of the reasons why I strongly believe the steroid increased by finasteride may be a mineralocorticoid over a glucocorticoid is because mineralocorticoids regulate salt and fluid retention. When my hair gets thicker from finasteride, most of the thickening occurs in a pretty short time frame... I'm talking like inside of a week. It also transitions from thick to thin, dry, and falling out very rapidly... Like days. What could cause hair to increase and decrease in thickness that quickly? Surely, it can't be that the hair has created new proteins and then lost those proteins only days later. That wouldn't make sense. But what would make sense is that they swelled up due to fluid retention, from possibly a mineralocorticoid, and then rapidly deflated after that mineralocorticoid decreased back to it's normal deficient concentration. There's a lot of speculation on my part here, but everything I've discovered through experimentation currently leads me in this direction.“





Matt Rogers said:

How do you feel about microneedling, I just started a regimen last week.

„I started microneedling mid December when I saw the results a guy on reddit got. I'm getting close to the third month and my hair certainly feels and looks denser, so I definitely think something is happening. I think it's too early to tell how effective it will be, though. The guy on reddit didn't start reallyseeing anything happen until after the third month. But after about 6 months, he pretty much regrew an entire head of hair. I'm not great with classifying it on a Norwood scale, but his loss was pretty extensive...like a 5 or a 6. After about 9 months that full coverage he attained became even denser and it truly looked spectacular. You would never know the guy had ever been bald in any way.

As far as finasteride and DHT, I would consider myself someone who most would say are extremely sensitive to DHT. I started losing at an early age (17) profusely. Without my change in diet, I can tell you with certainty that I would resume that nasty process and my scalp would burn, itch, and be inflamed.“


EndlessPossibilities said:

It’s why oral spironolactone works so well for people. Not because it’s an anti androgen. It’s because it has an affect on the mineralcorticoid and cause potassium sparing.


„I also agree with this. I have spironolactone, but have not experimented with it yet.“



EndlessPossibilities said:

Estradiol isn’t the key. Aromatase in my opinion is.


“So, I've done a lot of experimentation with finasteride and I have some very specific observations that have led me to believe that estrogens are possibly not as significant as I thought they were.

What I've discovered is that finasteride causes the HPTA to shut down steroid production, likely due to an increase in estrogens. After this happens, you have to stop finasteride for 2-3 months to let the HPTA recover before finasteride will be effective again.. and for me, finasteride is extraordinarily effective. If taken the way I've specified, my hair gets extremely thick and dark after a few weeks, stays that way for around a week, and then gets thin and begins to fall out again.

So, in an attempt to verify that these effects were due an increase in estrogens, I injected 250mg of testosterone after my hair had gotten thin and fallen out again. This DEFINITELY increased my estradiol, but it had absolutely no positive effect on my hair.. none whatsoever. So, I thought "ok, maybe I'm looking at the wrong estrogen.. maybe it's actually estrone.".. I tried the same thing with androstenedione and still nothing. I've also independently used both estradiol and estrone and get the same side effects as taking testosterone and androstenedione, respectively. For awhile, I thought that the finasteride had caused my body to downregulate aromatase in order to protect itself... which I think is logical, but.. at the same time, injecting testosterone and androstenedione sharply increased my estrogens and nothing positive happened to my hair. So, this ultimately led me to start exploring other steroids.

So, through my experimentation with finasteride, here is what I do know:

1. The positive effects I experienced from finasteride were NOT due to a decrease in DHT. If this were the case, the finasteride would have worked without the effects disappearing after a few weeks.

2. The positive effects are also likely NOT due to an increase in estrogens, though I still leave room for possibility.

3. The positive effects from finasteride ARE due to the increase of a steroid that would normally have been 5-alpha reduced OR another chemical or hormone that was increased due to the increase in that steroid that would normally have been 5-alpha reduced. To me this is what I absolutely DO know.

So I've researched what steroids are generally 5-alpha reduced and tried to determine which of them seems most likely to cause hair thinning and hair loss in BOTH men and women. I truly believe that, ultimately, men and women lose hair for the same reason. Sure, men generally lose hair in a different pattern than women do, but I believe the underlying cause is the same. Anyway.. I've been led to believe that the lack of a gluco- or mineralocorticoid that would normally be heavily 5-alpha reduced is responsible for the lack of volume and darkness of hair (basically thinning). To me, that points to a mineralocorticoid. Another thing that leads me to believe this is that when I take finasteride and experience the positive effects, it also affects my skin. My skin looks god-like for the short time my hair also looks amazing. The reason it looks so good is because it is retaining more water... it's very plump looking and full. Keep in mind, while all this is happening, my testosterone is SKY high (like 1200-1300 ng/dl) and my skin is also very oily... but not so much oily... more waxy. You might think it would be kind of gross, but it was quite the opposite. It had this waxy (not shiny), smooth sheen to it. So, I also know for certain that testosterone doesn't negatively affect hair in any way.

I have a very strong feeling that the mystery steroid I'm looking for may be 11-deoxycorticosterone... or possibly, indirectly corticosterone after 11-deoxycorticosterone has been hydroxylated through the 11b-hydroxylase pathway. I don't believe aldosterone is the culprit, though it is also 5-alpha reduced. If it were aldosterone, I'm sure that plenty of people would experience hair growth simply by taking licorice root extract. One thing that kind of irritates me is that there are so many steroids that no one really knows anything about... and part of this because some jackass concludes that a certain steroid is just some kind of intermediate to another more important steroid and has no physiological significance... kind of how you may hear that estrone is just an inactivated estradiol or less active estrogen. I think that's total garbage... I believe that each individual steroid has it's own physiological significance. Look up 11-deoxycorticosterone and tell me if you can find anything significant related to what it's function is in the body other than just be a "precursor" to another steroid. You might find that it's 5-alpha reduced version, dihydrodeoxycorticosterone, is a neurosteroid as well as the keto form tetrahydrodeoxycorticosterone.

So, what if the issue is that people who generally have fine, thinning hair that is falling out have low levels of a mineralocorticoid like 11-deoxycorticosterone that is made even lower due to 5-alpha reduction? Then finasteride starts to make even more sense... and also why some people experience this "shed". I never experienced a shed on finasteride until it stopped working.. and this happened because my body was simply just making less steroids due to the HPTA crash caused by finasteride. So, finasteride temporarily increases this steroid.. and then your brain's hormone regulatory center kicks in and decreases all steroid output to protect itself.. and then that steroid lowers in concentration again and you're left with thin shedding hair.”




“Some people also might say... "well if all that is true, then why do androgen receptor antagonists work for some people?" While l can still agree that DHT and other androgens (not testosterone) may be still related to hair loss, there is another possibility. If you take an androgen receptor antagonist, how is your body going to react to that? It will likely try to increase steroid production, either testicular or adrenal steroid production, because it isn't getting the appropriate level of androgen stimulation. To increase androgen production, the adrenals and testicles are increasing ALL steroids. They can't just selectively increase the steroid your body happens to need.

The same thing happens when you have a shortage of gluco- or mineralocorticoids due to an enzyme deficiency (either 21-hydroxylase or 11b hydroxylase). A shortage of these steroids causes an increase in adrenal steroid output because when you have ineffective conversion of steroids to the corticoids, you need more of them to suffice. And because of that, you're left with an excessive amount of 17a-OH progesterone, and perhaps 17a-OH pregnenolone, which leads to excessive production of androgens and estrogens.“



EndlessPossibilities said:

Aldosterone is 5alpha reduced?

Can you share where you found this info?

I find it hard to believe that aldosterone is reduced by 5ar. Because in that one article I pointed it out that DHT increased aldosterone.

You would thinking aldosterone would go down if it is 5alpha reduced right?


New mineralocorticoids: 5alpha-dihydroaldosterone and 5alpha-dihydro-11-deoxycorticosterone - PubMed

“I'm very careful not to put mental roadblocks on myself when I read something that I might not be able to fit into the bigger picture yet. I'm not sure how significant it is that DHT increases aldosterone. One thing that the study you linked mentioned was that it required supraphysiological levels of DHT to increase aldosterone... I think 300-1000ng/dl. That is really quite high and I think probably higher than the levels of most male pattern baldness sufferers. The study also implied that the increase in aldosterone didn't seem to be related to androgen receptor activation. It definitely has me curious as to what the implications are.

I do think that aldosterone would certainly go down in concentration being 5-alpha reduced... and because of that, the body would require a higher aldosterone production for normal function. This could have many implications... maybe the body can't keep up and you have chronically low aldoste.rone... maybe it can produce an appropriate amount of aldosterone, but it depletes you of upstream corticosterone or 11-deoxycorticosterone concentration. Maybe one or both of those steroids don't spend much time as themselves because they are quickly metabolized to their downstream steroids. In other words, their concentrations never get very high because they are enzymatically metabolized rapidly to corticosterone and aldosterone.

As far as the significance of aldosterone and hair loss... I'm not sure if it's an actual relevant player in the equation or if it's simply just a sign of something that's happening upstream.“


EndlessPossibilities said:

Also I think you got this backwards. Licorice root extract increase aldosterone

https://www.nejm.org/doi/full/10.1056/NEJM199110243251706

How to Eat Licorice Root


„What I meant is that if aldosterone were the mystery steroid that I'm looking for (since it can be 5-alpha reduced) and had positive effects on hair loss, licorice root would probably show signs of helping many of the people that take it.“



“Just for the record, I actually had my aldosterone level tested a couple months ago and to me it seemed pretty low. It's difficult to tell what is low and what isn't because the reference range is from 0-30 ng/dl... meaning that zero can be normal. Not sure how that makes sense, but I'm sure there are other factors like plasma renin that need to be considered. So my levels were:

Aldosterone 3.6 Range 0.0-30.0 ng/dl
Renin 0.698 Range 0.167-5.380 ng/dl

I had them tested out of curiosity and also because I'm having problems with frequent urination which led me to believe that my aldosterone was low. To me, those both seem to be on the lower end of the scale and I think there's a definite connection with my frequent urination. Something that's also interesting... the frequent urination goes away when I take finasteride. Whether that's due to an increase in aldosterone because it's not being 5-alpha reduced, or simply that the concentration of the upstream steroids (corticosterone and 11-deoxycorticosterone) increased to cause the increase in aldosterone... I'm not sure. It's definitely interesting, though... and I really think there's something worth discovering related to this area on the spectrum. I think companies are really going down the wrong path by assuming that androgens and androgen receptors have a bigger role than they actually do.“



EndlessPossibilities said:

Was your blood pressure super low?


„No... that's also pretty interesting. My blood pressure is around 110/73, but on finasteride it goes a little higher... somewhere around 120/80 and sometimes higher from what I can remember.“


“And the first though that comes to mind about that is: what if dihydroaldosterone helps in regulation of my blood pressure, but is insufficient in some way that causes salt wasting and frequent urination? I'm really not sure. It's perplexing and interesting. There's a whole lot we don't know in the field of endocrinology.“



EndlessPossibilities said:

Wow that’s excellent blood pressure. Mine is 125/85 last I checked. And I think finasteride reduced it for me

Are you hairy? Lol. Sorry for all these questions I am just curious not that I can infer solely based on symptoms and traits

A little over 3 months and finasteride has been amazing for me. The Insane libido I used to have feels normal now. Skin excellent and body hair slowed down. I often wake up with spontaneous morning wood.

„I am hairy... not on the back or anything, but definitely on the arms, legs, chest and face. Interestingly enough, during the few-week window that finasteride is effective for me, not only does the hair on my head get thicker and darker, but my facial hair and body hair also do. Sexually, finasteride wrecks me, though.“



“I think what's also important to note is that the significance of finasteride and its effect on hair loss (as well as other things.. like my frequent urination) is not related to DHT. It's related to 5AR. 5AR has far more significance than DHT in relation to hair loss... and it's because it affects so many other steroid concentrations when it's suddenly inhibited by finasteride.”



“So, one thing that I'll say is that there still is a possibility that estrogens and aromatase are what drives the success of finasteride.. And here's how that looks to me:

I believe that taking high doses of finasteride can give the body a short window of existence in which:

1. 5ar expression is nonexistent (because it's bound by finasteride)

2. Aromatase expression is as it normally is (I believe that higher DHT actually allows for higher aromatase expression, so the higher your 5ar expression is in the brain, the higher your aromatase expression will likewise also be... Because there is a balancing act between androgen and estrogen receptor activation)

3. Local production of estrogens is higher due to the fact that there is simply more substrate to be aromatized (there's no 5-a reduction of testosterone or androstenedione or any other steroid occurring, leaving far more substrate available for aromatization)

Now, if this is what is really going on... And it could very likely be... Then what it means is that increasing serum hormones like estrogens may actually be detrimental to hair growth because they cause aromatase expression to decrease (in order to control excessive estrogens)... and also that the hair follicle has limited or no access to serum estrogens. In other words, the estrogens (and possibly even DHT) must be created within the hair follicle to actually have any physiological effect. And obviously, the reason why finasteride will only work for me so well within a short window is because the body shuts down steroid production (putting you in a hypogonadal state to protect itself) and also lowers aromatase expression.

So, it's possible that this is why adding exogenous estrogens doesn't really do anything and can actually make things worse. Is this the answer? I really don't know. I would think that if estrogens were the answer, that taking a quick high dose of estrogens would cause a positive effect on hair, but it hasn't at all for me.

Another implication it brings to light is that if only the steroids that are created within the hair follicle have a physiological effect on the hair follicle, then theoretically, you should be able to take high amounts of exogenous DHT without affecting the hair follicle. In fact, I would think that it should be positive... That the body would increase its aromatase expression due to excessive androgenism. But I think that there are certainly people out there who have done this, certainly body builders, who haven't been experienced negative effect on hair.

So, this what leads me to believe that the mystery steroid that hair needs to grow properly is a mineralocorticoid or possibly glucocorticoid. I'm kind of stuck between these two lines of reasoning, though.“




DyingOfTheLight said:

Very interseting. I've read all your posts thus far and I'm intrigued. No idea whatsoever what mystery hormone attacks the follicle but I know for sure it's isn't (solely) DHT.


„So, the mystery hormone that I'm looking for is actually not a hormone that attacks the hair follicle. What I'm looking for is a hormone that does the opposite... causes hair to become thicker, darker, and to stay in your head. It's my strong belief that finasteride works not by decreasing something that attacks the hair follicle (DHT), but by increasing some other hormone that is normally 5-alpha reduced. The reason I believe this is because finasteride only works well for me for a short period of time... Basically while it has caused an increase in this "mystery" hormone.

Now, during this entire time and after, DHT is pretty low. So, I know for certain that a lack of DHT isn't the reason the hair becomes thicker, but rather the presence of some other "mystery" steroid that was increased by the inhibition of 5AR. If it were not so, my hair would stay thick and dark on finasteride indefinitely. Instead, what happens is that this mystery hormone, along with a bunch of other hormones that have also increased in concentration due to finasteride, cause an HPTA shutdown or crash. This results in the thinning, dryness, and shedding that comes afterward (because that hormone responsible for the health and proper function of the hair is no longer being produced in the higher concentration it was).

In fact, this is also what causes your shedding when you were coming off cycle and also from various other things that influence steroid and hormone regulation. It's also interesting to me that masteron itself didn't cause you to lose hair.. Which makes total sense to me. I don't actually believe that androgens or binding of the androgen receptors cause hair loss. What I do believe is that we're exploiting something else that is happening by inhibiting 5AR.

Another reason I strongly believe this is because the manner in which I take finasteride matters. If I take finasteride the way most people take it (1mg daily) the concentration of this mystery hormone doesn't really have a chance to get really high. By taking much higher doses (5-10mg daily), however, the mystery hormone increases sooner and higher in concentration.. Before the HPTA shutdown has a chance to occur. You're basically causing such a quick and drastic change that your brain doesn't have a chance to cause an HPTA shutdown quickly enough... And during this little window in time is where all the magic with finasteride occurs.“



EndlessPossibilities said:

You took 5-10mg a day? Woah and by magic regrowth? Or just thickening?


„It caused thickening of the hairshaft (I'm talking like double the thickness... Really significant), darkening of the hair, and induction of new hair growth (I got tons of new vellus hairs in my hairline). And keep in mind, all of this occurred in a very short period of time. It took maybe 3 weeks for the 5AR inhibition to stabilize and right around the third week, for maybe 3-5 days, my hair would just explode in thickness, darkness, etc. Whatever was increased created the perfect ideal environment in my skin and hair follicles for growth and health of the follicles. Afterwards, the effects would taper off and my hair would become dry, thin, and begin falling out again. Then the only way to make it happen again would be to stop finasteride for a few months, let my HPTA recover, and then repeat.“



EndlessPossibilities said:

The hpta shutdown thing you talk about scares me. It’s been 3 months and 2 weeks on fine and my hairloss has been halted for a month. Like I barely shed ever. Doing 1mg daily.


Also chem head

Thoughts on this
Effects of the 5 alpha-reductase inhibitor finasteride on serum levels of gonadal, adrenal, and hypophyseal hormones and its clinical significance: a prospective clinical study - PubMed

“Pretty much everything in that study reflects my experience with finasteride. It causes a sharp decrease in FSH and LH and one thing that's also important to note... And I believe this goes unnoticed when doctors look at lab work.. Is that people become androgen deficient while taking finasteride.

"At month 3, the dihydrotestosterone level decreased by 60%, while the testosterone level increased by 15%"

Testosterone increases 15% in concentration, so doctors may think that a man shouldn't be androgen deficient. What they fail to realize is that these concentrations are supposed to be dynamic and not static. What I mean by this is that in a person who isn't taking finasteride, the concentration of testosterone is at the level it is because it is being dynamically created and then metabolized by 5AR to DHT at a certain rate. Try not to imagine testosterone and DHT as two different things, but rather see both of them as part of the general supply of "steroid". Perhaps see it like this: all steroids represent the water in a flowing river. When the river branches off into other rivers and perhaps other smaller rivines, those represent the different types of steroids. By taking finasteride, you're essentially blocking the flow of the river from branching into another river or rivine. The level of the main river rises as a result of this (testosterone is increasing). But now imagine you have a guy that regulates the level of that main river and he sees that it's too high and that it could cause damage to things downstream. So, he shuts down the flow a little bit. The level still appears higher than it would normally be, but the total flow rate of that river has been significantly decreased because it lost an entire branch that it normally flows into.

This is exactly what's happening in finasteride users. To the untrained eye, lab work may seem to indicate that you testosterone levels are high and that you shouldn't be androgen deficient, but in reality, the flow of your steroid has actually stagnated... You're getting less metabolic throughput of steroid. That's why guys end up feeling like death from finasteride.”



EndlessPossibilities said:

What’s interesting is that study was on 5mg doses. Have your tried 1mg. Cause I heard at that dosage from other studies LH doesn’t change much


„I have tried 1mg doses.. It doesn't work the same way. And it's because the goal is to shock the system and increase the concentration of that mystery steroid before the body shuts down steroid production. But when I was younger and first tried finasteride at 1mg, I would say that it probably worked just as well as the 5 mg did when I was using it.

Finasteride is dangerous really. It does exactly what it's supposed to do, so it's not like it's evil or anything. The problem is that it's just like dropping a nuclear weapon on a city to kill one person. I'd say that if hairloss were really due to a lack of estrogens because all the substrate (testosterone and androstenedione) is 5 alpha reduced much more than its aromatized, then the only real cure will be genetic alteration to eliminate 5AR expression in the skin and hair.

There is a lot of regulation and constant feedback loop tuning that has to occur to get your body back to normal after taking finasteride. You lose both 5AR and aromatase expression from taking finasteride and the only way they go back to normal is through a slow process of 5AR expression increasing, then aromatase increasing, then crash from estrogen increase from the aromatase increase. Then more 5AR increase... And it just slowly keeps doing this until both 5AR and aromatase are at optimal levels.“



EndlessPossibilities said:

See that Hpta shutdown is accurate but I don’t think it applies to people who are on the lower spectrum of test levels. To me I’ve always been kinda low very hard for me to gain muscle. I really hope I don’t get shutdown


Now I agree with you on other things having a play with hairloss. But what do you make of the studies that showed dht directly affected follicles negatively. Or the buildup of DHT in balding scalp?

“I believe that there is definitely merit to it. However, I know for sure that eliminating DHT doesn't make my hair optimal or cause it to grow or look thick and healthy. I think the reality is that the presence of 5AR in the skin and hair simultaneously causes the presence of something that's not really good for the hair (DHT) and the lack of presence of something that is required for healthy growing hair (not sure what that is, but it very well could be an estrogen). So, DHT by itself isn't the answer. It's both decreasing DHT locally in the scalp and simultaneously increasing some other hormone. You need both to be successful.“





EndlessPossibilities said:

I so agree with you. We need to figure this out you and me. Lol

Am I right to say that when 5-ar goes down. aromatase increases

„It doesn't increase. It's actually the same for awhile, but it will decrease if the lack of DHT in the body causes excessive estrogenism. This is why I believe FSH decreases when taking finasteride. I believe that FSH plays a role in increasing aromatase expression and the body will attempt to lower aromatase expression when there's an excess of serum estrogens.

What does happen, though is that the androgens that would normally be 5 alpha reduced are now available to be aromatized instead. Androgens have a higher affinity for 5AR than for aromatase. So, a match between one 5AR protein and one aromatase protein favors the androgen binding 5AR.. The equilibrium favors production of DHT over estrogens. If it were not so, the body would have no real way of dealing with the dangerous state of excessive estrogenism.“




“One of the things that people lack in understanding that I think holds us back in terms of research on hair loss is that you can't determine what is good or what is bad for hair by measuring serum hormones and trying to correlate those numbers with what's going on inside the miniature organ that is the hair follicle.

Is estrogen good or bad for hair? Yes. It is both simultaneously good and bad. High serum estrogens are bad for your hair because they cause the body's regulatory mechanisms to lower individual tissues' aromatase expression. Having high serum estrogens ultimately causes the concentration of estrogens within the scalp to be low. You want the follicle to create the estrogens like it is intended to do and there will be a much higher concentration within the follicle.

Is DHT good or bad for hair? Yes. It is also simultaneously good and bad. Higher serum levels of DHT (and especially in the brain) are good for hair because they cause the bodies' tissues to upregulate aromatase expression. High levels of DHT that is created within the follicle by 5AR is bad for hair. And it's bad for two reasons.. It's bad because DHT binding the androgen receptor causes it to express a gene that signals the hair follicle to shed AND the 5AR enzyme itself takes away aromatizable substrate (aka testosterone and androstenedione) which would otherwise be aromatized to some form of estrogen if there were no presence of 5AR.“





EndlessPossibilities said:

So to recap for the scalp we need more testosterone and more aromatase.

I think I am missing something but I bet money that test is actually super good for hair I mean people say zinc and vitamin d help. All known to increase testosterone.


„Yes. We definitely want more testosterone and higher local aromatase in the scalp and skin for men. Serum testosterone (and androstenedione) is our supply for estrogens in tissues via aromatization.“


EndlessPossibilities said:

Testosterone increases aromatase expression. Not dht. Dht does not aromatize.


„Both Testosterone and DHT increase aromatase expression. This phenomenon is not dependent on whether DHT is aromatizable. It's dependent on the binding of the androgen receptor. In fact, DHT will increase aromatase expression more than testosterone. The problem is that DHT itself signals the hair follicle to shed and the enzyme that created the DHT in the first place takes away from the supply of testosterone (or androstenedione) that can be aromatized to an estrogen.“



EndlessPossibilities said:

Dutasteride which many people have reported destroyed their hairline probabl lowered their test levels too.


When my natural test levels got low that’s when I noticed the most amount of hairloss.

And natural test levels are treated much differently than injected test.


Any steroid that is exogenously supplied is going to negatively affect enzyme expression in all types of tissues throughout the body due to it's effects on the HPTA.

The goal is this: The hair follicle must create it's own supply of estrogens through aromatase and it cannot get this supply from serum estrogens. 5AR interferes with this process by taking away testosterone (and androstenedione) supply and, at the same time, its product (DHT) unfortunately also happens to signal the hair to shed. The presence of 5AR in the scalp and skin screws you from two different directions.





EndlessPossibilities said:

You said it perfectly. Like absolutely perfect.
Like I think this is truly it.


3.5 months on finasteride. Slower body hair. Hairloss seems to have stopped. No estrogenic sides. Although I will say my **** and balls have less feeling but not necessarily too little. Because frankly I always felt like I was a horn dog. Like a ridiculous Horndog. I can Masturbate once a day. Even twice. It take a a lot more to get me hard which I think is how I should’ve been. The level where I was at felt like it was ruining my life.

I am so excited to try the dexamethasone tmrw. 1% dexa. Topical

Click to expand...

„I'm pretty interested to see how dexamethasone works for you. I considered getting dexamethasone to try, but I decided to get prostaglandin E2 instead because it's more potent at increasing aromatase expression. It definitely made my hair thicker, but it was less significant than finasteride.

This makes sense though.. we still have to take care of the 5AR problem. Getting rid of 5AR in the skin and hair follicle takes care of both problems. It takes care of the lack of enough estrogens being created within the follicle and the synthesis of DHT within the follicle simultaneously.“



„Also, if these things work for anyone... dexamethasone, prostaglandin E2, ricinoleic acid from castor oil, and anything that upregulates aromatase expression... they should work pretty much overnight or within a couple days. They should work very quickly and their effects should also fade quickly if a daily routine is not maintained. They shouldn't take weeks or months. If it doesn't work in the first few days, it's probably not going to work at all. I've used both ricinoleic acid and prostaglandin E2 and they both work pretty much overnight at increasing thickness of the hair.“



Timii said:

I' ve read all of the posts in this thread. Very interesting theories. But I have a question: What is the role of inflammation? @ChemHead @EndlessPossibilities

„It certainly plays a role. Everyone has inflammation, though. The difference is that people who don't experience hair loss or skin problems have more favorable genetic enzymatic expression that creates an environment in the skin and hair follicles that is plentiful with steroids that are anti-inflammatory. Estrogens that are created by enzymatic metabolism intracellularly in the skin and the hair follicles cause a cascade of genes to be expressed which cause the release of growth factors and anti-inflammatory chemicals.

Even the healthiest of people experience daily inflammation in the skin and hair follicles. The difference is that those with good looking, healthy hair and skin are more equipped to deal with that inflammation. So, attacking this problem from an anti-inflammatory perspective and attacking it from a "steroid" perspective are actually one in the same. The inflammation goes away if you can provide the skin and hair follicles with the proper environment for normal hair growth.“



“f you're interested in knowing more about fibrosis and the connection to mineralocorticoids, glucocorticoids, and the MC and GC receptors, look into aldosterone. There's a couple good studies out there that talk about increasing elastin synthesis and decreasing collagen synthesis using a MC receptor antagonist (spironolactone) and aldosterone.

Search for:
human skin as a target for aldosterone

Mineralocorticoid receptor antagonists - a new sprinkle of salt and youth

Aldosterone and mineralocorticoid receptor antagonists modulate elastin and collagen deposition in human skin

Re-epithelialization of pathological cutaneous wounds is improved by local mineralocorticoid receptor antagonism

Tissue fibrosis: a principal proof for the central role of misrepair in aging

These are the all studies that convinced me that mineralocorticoids, glucocorticoids, and their receptors may play a role in hair loss.“



“To be clear, I don't think testosterone directly helps hair grow. Testosterone in equilibrium with androstenedione, however, indirectly helps by providing a supply of estrogens through aromatization within the skin and hair follicles.“


“I also believe that there is a connection that needs more exploration between glucocorticoids, mineralocorticoids,and their receptors AND aromatase, estrogens, and the estrogen receptor.”


“Another couple studies that got me interested in the connection between mineralocorticoids, MC receptors, and estrogens:

The effect of spironolactone on aromatase activity

The effects of estradiol and estriol on plasma levels of cortisol and thyroid hormone-binding globulins and on aldosterone and cortisol secretion rates in man

One of these studies shows that spironolactone significantly increased serum estrone, but had a statically insignificant different in serum estradiol concentration. I don't remember which one, though. It's been awhile since I've read them.“




Capone said:

We need 5AR for our skin or else we’ll all be running around like Keith Richards.

„I actually don't think that we need DHT for our skin.. at least not in any significant amount. I believe that DHT is almost like an inferior, but necessary, version of testosterone for when the body isn't functioning properly. I feel that it's the body's way of protecting itself from excessive estrogenism. When you see guys that have really good looking skin and hair... like godlike.. it's because they naturally don't express 5AR in the skin or hair. So, most of the androgens in their skin and hair are metabolized to estrogens and the rest are left for masculine features like facial hair growth. The guys that have very little testosterone in the skin probably don't end up having much facial hair or oil in their skin.

So, anyway, somewhere along the path of our geneology, our ancestors probably encountered some kind of chronic environmental stress over generations that caused us to express 5AR in places it didn't really belong in order to protect itself.“


„So, in the spirit of the original post, I've come across another person who has experienced thickening and cessation of hair loss with an anabolic steroid. Rather than anavar, this person experienced thickening while using nandrolone. After some time thinking and looking at the structure of nandrolone, I've determined that the mechanism for this is similar to anavar, except that nandrolone has the potential to actually work better. I will explain further in the next post.“


“So, I'm going to post here what I've explained to this other person with regard to how and why he experienced thickening of his hair while using nandrolone:


Nandrolone has a very high affinity for the androgen receptor.. much higher than testosterone and probably on par with or higher than DHT. So, in a competition with DHT, nandrolone will win at binding the androgen receptor at least 50% of the time (given equal concentration of both steroids) and possibly more. I’m unsure of the relative binding affinity of nandrolone with respect to DHT, so I can’t definitively say that it binds with significantly greater affinity, but it’s safe to assume that they’re both at least on par with one another.

Nandrolone also has relatively the same binding affinity for the 5AR enzyme that testosterone has.. possibly higher. So, it’s safe to assume that in competition with testosterone, nandrolone will win at binding 5AR at least 50% of the time (given equal concentration of both steroids).

Nandrolone is very similar to testosterone in structure. The only difference between the two is that nandrolone is missing a methyl group at the 10-carbon position shared by the A and B rings of the steroid. This is why it’s also called 10-Nortestosterone (or 19-Nortestosterone since that methyl group is actually classified as the 19th carbon of the cholesterol steroid backbone). The nor prefix simply means that the steroid is missing that methyl group at the specified position on the steroid backbone. So, this missing methyl group is actually pretty important because, without it, nandrolone cannot be aromatized to an estrogen. Normally, in testosterone, this methyl group is enzymatically hydroxylated, oxidized to a carboxyl group, and then made to leave as a formate ion with the help of an enzymatic peroxide. Since nandrolone is missing this methyl group, this doesn’t happen because it has no way to create a good leaving group.. it has a relatively stable proton instead.

Ok, so if you’re with me thus far, here’s why all three of those things are significant:

1. Nandrolone is not DHT. So, when nandrolone binds the androgen receptor, it does not cause the same gene transcription that DHT causes and so, very likely, does not cause the hair to shed and thin like DHT does. No two steroids that are unique cause the same gene expression. This is why it’s stupid when people talk about the androgenicity, or estrogenicity, or binding affinity, or strength of one steroid vs another while totally ignoring (or being unaware of) the fact that they cause unique genetic expressions. This is why testosterone does not contribute to hair loss and DHT does.


2. When nandrolone is in competition with testosterone for 5AR, it is going to bind at least half the 5AR enzyme present in tissue if both steroids are present in the same concentration. This means that at least 50% more testosterone will be available for aromatization than would normally be without the presence of nandrolone. If you can imagine 5AR as a destructive hungry monster, you’re essentially trying to feeding it something else instead of testosterone because it results in the synthesis of less DHT and an increase in available testosterone to be aromatized. Now, when nandrolone is reduced, it forms 5-alpha dihydronandrolone (DHN). Unlike DHT, DHN happens to have a weaker affinity for the androgen receptor than its non-reduced steroid. Remember, DHT and DHN are also two different steroids and do not cause the same genes to be expressed when they bind the androgen receptor. However, if DHN caused the expression of genetic code that led to hair loss, it would have a lesser effect than DHT due to its lower binding affinity to the androgen receptor. So, to recap, nandrolone will bind to 5AR and act as kind of a competitive inhibitor of the enzyme, freeing up a higher concentration of testosterone to be aromatized.


3. Because nandrolone is non-aromatizable, nandrolone and dihydronandrolone will not cause the steroid regulatory systems in the body to downregulate aromatase or estrogen receptor expression. It will actually do the opposite. Binding of the androgen receptor will cause an increase in aromatase expression. This is important because hair loss sufferers likely have an aromatase and/or estrogen receptor insufficiency. I happen to think that most have an estrogen receptor insufficiency and, therefore, require higher levels of estrogens to provide sufficient estrogenic activity in the hair and skin compared to others. So, as a teenager, you have higher levels of androgens and maintain high aromatase expression and this results in oily skin and acne. As you age, steroid production decreases and less estrogens are created and there’s no longer enough estrogenic activity to keep your hair follicles healthy. For some this process happens more gradually and for others it’s aggressive and happens at a very young age. I believe it probably happens as a result of excessive aromatase expression in the brain and in other important tissues and when the body goes through puberty, this causes excessive estrogenism. The body’s only way to defend itself against this is to increase expression of 5AR to preserve androgens from being aromatized.

So, there’s a couple reasons why taking both deca [nandrolone] and testosterone on cycle contributed to hair thickness and cessation of loss. The deca [nandrolone] acted as a competitive 5AR inhibitor, but, at the same time, also bound the androgen receptor to increase [or at least maintain] aromatase expression without causing hair loss. (This is great compared to finasteride. Finasteride binds 5AR and you end up with less androgen receptor activation. This will ultimately cause aromatase expression to decrease and also leaves your entire body with excessive estrogenism due to testosterone being aromatizeable.)

Obviously, since you took the deca [nandrolone], your endogenous testosterone levels are going to decrease significantly. If you had not taken deca [nandrolone] with a base of testosterone, you very likely wouldn’t have experienced the benefits for the hair, but I will admit that it’s still possible.“


„It's really all about the degree to which a person expresses 5AR and aromatase. Someone who expresses high 5AR and low aromatase is going to experience severe hair loss. Someone who expresses high aromatase and moderate 5AR will generally have a thicker hair shaft diameter, but they will also lose a moderate amount of hair (their hair won't be as dense as it could be... there are a lot of women with this issue, but most would look at them and not think that they're suffering from any type of hair loss, despite the moderate loss they experience). Someone who expresses low to moderate 5AR and moderate aromatase will generally have a full head of hair, but maybe a moderate to fine hair shaft diameter. Someone with low 5AR expression and high aromatase expression will have a full head of hair and their hair shaft diameter will be pretty much as thick as it's capable of being for their ethnicity.“






EndlessPossibilities said:

Dude you are so full of knowledge it’s insane. If all the passionate member of hairlosstalk could just meet up in a fat auditorium and get paid monthly. We could cure this damn disease in 6 months. Lol


2 billion dollars of funding

„I've been doing this for awhile.. I've used my body as a lab for experimentation or over a decade, so that helps. I have a background in synthetic chemistry as well. If I had financial resources, I think I probably could have already developed an effective way to treat this disease with the help of other professionals that are well versed in methods of biochemistry.

I've actually already developed a drug.. it's very similar to dutasteride (technically, it's functionally identical), but I developed it to only work in tissues where it can be activated. So, it is essentially a shielded version of dutasteride that is physiologically inactive in the body unless activated from a device externally. With no financial resources or spectroscopic equipment, though, repeated testing of a compound for functionality would be expensive. I can have the compound made in china for around $2500, but then I need to verify the structure through mass spec, NMR, and HPLC. Then, I would have to set up a test matrix of probably somewhere between 50-100 test samples, perform proof of concept outside the body, and then perform HPLC on those samples to determine which sample to move forward with. Only then could I possibly test on the body and if that doesn't work out, the compound needs to be revised to alter function and the whole process starts all over. Not easy for one person to do, but no problem for a company with resources.“






And finally, page 9 cause of baldness:


Capone said:

For me personally, whenever I use a 5ar blocker my skin looks aged. Deeper, more pronounced lines. Could be the lack of DHT. If estrogen is good for skin then why do men’s faces and bodies start to age as it rises?

“This is due to the changes in enzyme expression and steroid production caused by 5AR antagonists like finasteride. Because the effects are not localized, it causes a downregulation of aromatase along with 5AR. I don't recommend you do this at all (especially since I've already done it countless times), but the way one could prove this would be to take high dose finasteride (5-10 mg daily) for a few weeks. What will happen is that your 5AR will be bound faster than your body will be able to react to the changes and your aromatase expression will still be high like it would be if you were still producing normal amounts of DHT. This will leave your hair and skin with high concentrations of both testosterone (and/or androstenedione) and estrogens that result from the aromatization thereof.

To answer your question about why men's skin starts to age as they age.. this is because serum estrogens increase with age causing a decrease in aromatase expression. So, what you end up with when you have high estrogen concentration in the blood is that the body will adjust to lower this... and the only way it can do this is to globally decrease aromatase expression. Thus, you end up with a more acceptable serum concentration of estrogens (or the best your body can do with its adjustment) and no longer a high enough aromatase expression in the skin to produce enough estrogens locally for healthy, supple skin. There can be a multitude of reasons for this, but I'm not really sure why it happens to begin with. For some people, being overweight could cause this (excess fatty tissue will aromatize androgens and increase serum estrogen concentration), but I think a more likely explanation is that an enzyme that deactivates estradiol and estrone may be missing or insufficient. So, basically, when the body is finished using the estrogen locally, it never gets metabolized and eliminated from the body. This stagnates estrogen synthesis... you end up with a bunch of junk estrogens in serum that should be eliminated, but can't be for some reason. So, the body adjusts to lower estrogen synthesis in all tissues to manage the serum estrogens. I actually feel like this is likely the genesis of hair loss. It's what causes 5AR expression to increase and aromatase to lower... in order to offset the effects of excessive serum estrogens.”



EndlessPossibilities said:

Dude I think you finally cracked it !!

This explains why after steroids hair loss begins. Estrogen rises like crazy and this causes down regulation of aromatase.

„I have to reiterate that many people have naturally low aromatase expression in the skin and hair and are much more susceptible to hair loss. Whether this is due to simply having genetically lower expression or due to a lack of enzymes that metabolize estrogens for elimination (causing lower aromatase expression), I'm not sure. There are plenty of guys out there that are able to run steroid cycles that are relatively unaffected by them regarding hair and it's because they have higher aromatase expression and lower 5AR expression. If one of them were to really pay attention to their hair and document changes while on cycle, I would not be surprised if they noticed a little decrease in the thickness of their hair... especially while using an aromatase inhibitor or a SERM.

So, there are really quite a lot of paradoxical things that are going on with hair loss and because of this, as a whole, the community of biochemists and clinical researchers working on it don't have a clear view of what causes it and we end up with drugs that will never really work. A drug that targets 5AR (unless its action is 100% local to the skin and hair follicle) will take care of DHT binding the androgen receptor, but will ultimately downregulate aromatase. A drug that targets the androgen receptor (an androgen receptor antagonist) will also take care of DHT binding the androgen receptor, but this will also down regulate aromatase expression because binding of the androgen receptor causes expression of aromatase to increase. So, what happens is that both of these types of drugs will work for a short time (some longer than others) and then the body will adjust its aromatase expression and they are no longer effective.

People wonder why they begin to shed when using finasteride or RU58841 after awhile and this is the exact reason.. it's not part of the "phases" of the drug doing its magic.. it's because aromatase has been downregulated.. and riding out the storm by continuing to take the drug is not going to improve things. It's done. Aromatase expression has been lowered and the only way to get it back up is from the appropriate androgens binding the androgen receptor (probably in the hypothalamus, but there's also evidence that binding androgen receptors locally causes an increase in aromatase expression). I believe that FSH is responsible for a systemic increase in aromatase expression, but I'm not sure how because there's really not a whole lot of clinical research on FSH. It think that if someone taking finasteride were to take FSH, their aromatase expression would increase, but I also think it wouldn't be healthy.. there's a reason why the aromatase expression was downregulated to begin with.“

 

[LeeLemonoil]

That's about as insulting as it gets, i try to do the exact opposite, share what i have come to know. I may be wrong but i certainly don't try to argue fallaciously or deceptively.

You did. But I apologize if it came about as insulting, it wasn’t meant that way.

Here is where you were clearly sophistic, and it could be understood as unfriendly intention since you used it to try to falsify a little theorem in progress wholesale:

You said „Nlrp3 overactivity isn’t the cause of hairloss, facial tension is“

That’s hairsplitting or sophism. It may be so, but only as a part of a causal chain - of which nlrp3 might also be part downstream. If offered a hypothesis thereon in response to you to.
Also, with the same logic or argument you apply your theory can be falsified off-Hand as well:
Facial tension is not the cause of hairloss, because facial tension has caused itself. So the causes of facial tension are the cause of hairloss.

I appreciate very much everyone that shares his knowledge and experience at RPF, in whichever topic.
And I didn’t look up your posting history . If our care to share a concise version of your
facial tension theory here pls do so. What mechanisms specifically and additionally are at work?
And im also interested in hearing what other conditions you think are connected to facial tension