Trying to understand the complicated world of the hormones!

Why I'm I balding?

1. Let's agree that it's caused by genetic hormonal sensitivity and/or/also/equals to/ micro inflammation in hair follicles, correct?
2. When testosterone molecules attaches to 5-alpha reductase the enzyme codes testosterone into dihydrotestosterone, correct?
3. This process it taking place both in the blood but also in the tissue, potentially on all places 5-alpha reductase is located.
4. The newly formed DHT is transported in the blood stream (serum) and when it gets in contact with hair-follicle tissue cells it attaches
to the androgen receptors located there and sending information into the core of the cell telling the "CPU" to suspend production and go into eternal coma, correct?
4.1 What happens to DHT produced in the tissues?
5. Consuming finasteride will actually inhibit the function of 5-alpha reductase by binding to it and thus limiting the ability for testosterone to get converted, resulting in less DHT. Correct?
5.1 Less in both serum and tissues? Or will it be a lowered tissue level when the tissue receptors notice the lack of serum DHT?
6. Less DHT means less destructive signals into the genetically sensitive core of the cell, correct?
7. Consuming finasteride lower levels of DHT in body and raising levels of testosterone, correct?
8. Where does progesterone and allopregnalone fit into this equation?
9. Does depression from finasteride mainly be caused by altered levels of the hormones mentioned in 8. ?
10. What happens with estrogen when more testosterone is available and what's up with aromatase?
11. Anything else that is important? Like TGF-B and such..

Please try to keep the medical terminology as simple as possible!

Misirlou - DHT isn't really bad, but it is a messenger to hair follicle dermal papilla. DHT sends a message to a protein called dickkopf 1. dickkopf 1 is the most upregulated genes in balding persons. Their dermal papilla cells were found to be high in it and the more bald you are, the more of it is there. When dickkopf 1 or DKK-1 is blocked, there is a significant reversal in hair loss.

DKK-1 is responsible for the inhibition of the growth of outer root sheath cells and their death. DHT triggered DKK-1 is involved in DHT driven balding. Of course there is also TGF-Beta and the subsequent MMP-9 that follow, which are DHT driven as well.

5-alpha reductase is the enzyme that also converts Brain 5-alpha-dihydroprogesterone and allopregnanolone.

5-alpha-dihydroprogesterone and allopregnanolone are considered neurosteroids. 5alpha-dihydroprogesterone binds with progesterone receptors for DNA activities (transcription factors). Allopregnanolone binds to gamma-aminobutyric acid GABA receptors.

In plain English, this means that without 5-alpha reductase, these two important neurosteroids are in very short supply, which will increase anxiety, depression and isolation tendencies.

DHT itself has important roles in the body. During child development (fetus), DHT in short supply will cause ambiguous genitalia or rather, a combination of male and female sex organs.

Additionally, DHT has been found to be important in muscle mass. Without enough DHT, muscles will be less pronounced.

Not surprisingly, DHT is also involved with the voice, beard hair and auxiliary hairs. Ear and nose hair I could do without, LOL, but it's responsible for that too.

When men age, into the years of the 40's, 50's and beyond progesterone levels decrease. This will increase enlargement of the prostate in later years since estrogen begins to become more and more prominent and with little progesterone, more DHT comes into play. Estrogen is responsible for enlargement/proliferation of tissues (hyperplasia), not DHT. Interestingly supplying more DHT to an enlarged prostate will shrink the prostate.

Finasteride and other irreversible 5-alpha reductase inhibitors (drugs) long term, may increase possibilities of neurodegeneration (think Parkinson's and Alzheimer's).

Testosterone is usually increased with 5-AR blockers. In the minority, there are those who have a highly negative reaction to finasteride, such as "reflex hyperandrogenicity." This is where DHT is actually increased.

1. Would you concider a limited daily dosage of .25mg finasteride to be too much?
2. What will down-regulate this DKK-1?
3. Do you guys believe that these terrible side effect stories online always are caused by finasteride?
4. Saw Palmetto is seldom recommended, any thoughts on this?

Misirlou - .25 mg of Finasteride from what I have read and heard is supposed to be as effective as full strength.

What about DKK-1? This is a tough thing to figure out. Short story is, I don't know of anything yet that definitely halts DKK-1 in anyway strong enough.

Lithium chloride, aspartate, or as orotate is a DKK-1 antagonist. I'm not sure how effective it is--I have certainly tried it both internally and topically.

There is only one documented way to epigenetically silence DKK-1. That would be CpG island, a promoter of hypermethylation. In studies in oncology (cancers), there is research showing that DKK-1 turns off Wnt proteins involved in cancer proliferation.

One of the major ways to prevent colon cancer involves the use of methylators such as Folic Acid, which reverses {Hypo}Methylation. Also agents like Trimethylglycine (Betaine), Pyridoxal 5'-phosphate (P5P), the result of the hepatic (liver) conversion of B6, and Methylcobalamin (Superior form of B12). Forget about these for a moment, because I am sure that many of us have taken plenty and nothing has worked.

However......

High dose folic acid maybe helpful.

"Normal" doses of 400 micrograms maybe inadequate when it comes to Folic Acid. A five Milligram dose (5,000 MCG) is in order. This is all theory though, as perhaps it requires hypermethylation via CpG island. But interestingly, I heard that high dose folic acid (5 mg) grows hair. Funny that I have never actually tried it--that dose anyway. This is an orthomolecular dose (excellent for hypertension), it also improves endothelial function in diabetics, so this makes it intriguing.

BMP-4 (Bone Morphogenetic Protein) is one of several upstream regulators of Dkk-1 expression, so inhibiting BMP-4 is another route. This is one reason why Vitamin K2 is good to have in supply as a shortage their be allow too much BMP-4.

Misirlou - Almost forgot about Saw Palmetto. 10 years ago I wrote a book on Saw Palmetto and hair loss, plus Beta Sitosterol. If you take enough, especially Beta-Sitosterol (which is the primary active constituent in saw palmetto) you can acquire sides similar to finasteride.

Saw Palmetto is weaker than Beta-Sitosterol, but it is not strong enough to completely halt hair loss--but it may buy some time.

I've used it for years and do not miss it at all.

1. Topical beta-sitosterol would be useless too?
2. .25mg would still be hazardous for the body in the long run?
3. Is it impossible that inhibitation of the protein DKK-1 leads to unwanted side effects?
4. Any sides from 5mg daily dosage of folic acid?
5. What is the healthy limit for vitamin K2 / day?
6. You said DHT is important for muscles, what do you mean and do you have any study about that?
7. what are the main changes usage of finasteride leads to when talking "hormones" (increase of / decrease of)?

CausticSymmetry wrote:this means that without 5-alpha reductase, these two important neurosteroids are in very short supply

But the body increased production of 5-alpha reductase with it feel it's not converting enough DHT (due to finasteride) ? The enzyme is not the threatened one, right?

Misirlou - Topical Beta-Sitosterol is a good idea, and it has been used. I've never tried it, but there's a guy name Joe who developed a formula called Super Zix II, which contains it.

I'm not sure how risky .25 mg of Finasteride is verses full strength.

Inhibiting DKK-1 is somewhat of an unknown if it is done chemically. I checked into a patent on it one way to silence it.

http://www.faqs.org/patents/app/20080293053

I had made another thought about folate or folic acid and that is that somewhere between 30% or more of the population cannot utilize the majority of folic acid supplements; they have difficulty converting the folic acid into real active folate.

L-methylfolate or what is called Metafolin is the active form. I believe that this may aid in the epigenetic silencing of DKK-1. I just placed an order for this stuff and will see if I notice any difference.

Side effects from 5 mg of folic acid? Regular folic acid (non-converted form) can diminish or interfere with B12, so usually the two should be taken together. However, if you use L-methylfolate (the active form), then extra B12 is not necessary.

Healthy limit for K2 per day? I do not know of a limit. There are several forms of Vitamin K2, the type that is derived from meat and dairy sources have a more limited half-life than say MK-7 (Menaquinone-7) does. It's impossible to overdose on this as far as I am aware.

I'll have to find the study on the muscles, because looking at others, it doesn't seem conclusive.

Misirlou - Regarding the neurosteroids, the enzyme 5-alpha reductase is needed to make dihydroprogesterone for example which plays an important part of mood regulation and neural health. From some of the studies I have seen, and knowing that a progesterone deficiency can result in neurodegenerative diseases is a concern.

Here's two different studies relating to finasteride and what effect it has on neurosteroids.

Brain Res. 2006 Apr 26;1085(1):49-56. Epub 2006 Apr 3.
Possible involvement of 5alpha-reduced neurosteroids in adrenergic and serotonergic stimulation of GFAP gene expression in rat C6 glioma cells.
Morita K, Arimochi H, Itoh H, Her S.

Department of Pharmacology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. km@basic.med.tokushima-u.ac.jp

Influence of adrenergic and serotonergic stimulation on glial fibrillary acidic protein (GFAP) gene expression in rat C6 glioma cells was first examined as an in vitro model experiment for investigating the neuronal regulation of glial cell differentiation. Stimulation of these cells with isoproterenol and serotonin elevated GFAP mRNA levels followed by an increase in its protein contents, thus suggesting that both adrenergic and serotonergic stimulation might induce the differentiation of the glioma cells. In addition, progesterone and its 5alpha-reduced metabolite dihydroprogesterone also elevated GFAP mRNA levels in rat C6 glioma cells, consistent with their stimulatory actions on GFAP gene expression observed in rat astrocytes. Further studies showed that the elevation of GFAP mRNA levels induced by isoproterenol and serotonin as well as progesterone was abolished by pretreatment of the glioma cells with finasteride, an inhibitor of 5alpha-reduced steroid production. Moreover, the stimulatory actions of isoproterenol and serotonin on GFAP gene expression were inhibited by pretreatment with a GABA(A) receptor antagonist bicuculline and a progesterone receptor antagonist RU486. These findings suggest that both adrenergic and serotonergic stimulation may indirectly activate GFAP gene expression probably through the production of 5alpha-reduced steroid metabolites in rat C6 glioma cells, proposing the possibility that 5alpha-reduced neurosteroids may play a potential role in the neuronal regulation of glial cell differentiation.

J Mol Neurosci. 2008 Mar;34(3):193-200. Epub 2008 Jan 25.
Progesterone pretreatment enhances serotonin-stimulated BDNF gene expression in rat c6 glioma cells through production of 5alpha-reduced neurosteroids.
Morita K, Her S.

Department of Pharmacology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan. km@basic.med.tokushima-u.ac.jp

Tricyclic antidepressants and selective serotonin reuptake inhibitors are considered in theory to induce the outflow of neurotransmitters, norepinephrine, and serotonin from the synapses as a consequence of inhibiting their reuptake into the nerve terminals, resulting in the stimulation of glial cells surrounding the synapses in the brain. Then, we have investigated the direct actions of neurotransmitters on glial cell metabolism and function using rat C6 glioma cells as an in vitro model system and suggested that these neurotransmitters induce their differentiation probably through the production of 5alpha-reduced neurosteroids. On the other hand, the stimulation of the glioma cells with serotonin has been reported to enhance brain-derived neurotrophic factor (BDNF) gene expression, which may be closely related to the beneficial effects of antidepressant drugs. In the present study, to evaluate BDNF expression in differentiated glial cells, the glioma cells were pretreated with progesterone, and the effect of serotonin on BDNF messenger RNA levels in these cells was examined. Progesterone pretreatment enhanced the stimulatory action of serotonin on BDNF gene expression, and the enhancement of serotonin action observed in the cells pretreated with progesterone was almost completely abolished by finasteride, an inhibitor of the enzyme involved in the production of 5alpha-reduced neurosteroids. These findings propose the possibility that neurosteroid-mediated glial cell differentiation may result in the enhancement of serotonin-stimulated BDNF gene expression, which is considered to contribute to the survival, regeneration, and plasticity of neuronal cells in the brain, and hence, leading to the improvement of mood disorders and other symptoms in depressive patients.

IH, im currently using metafolin, for couple of days I used about 3mg of the stuff and it raised my histamine like CRAZY. On a low dose of it now (400mcg BID)

Joejoebaggins - I was checking out some of the comments by the users and was reminded of how it helps in the production of serotonin, dopamine and norepinephrine. Pretty powerful methylator metafolin is.

Joejoebaggins - Did you hear that two-hour interview on iodine by chance? I learned that iodine is one of the most powerful anti-histamines.

CausticSymmetry wrote:Joejoebaggins - Did you hear that two-hour interview on iodine by chance? I learned that iodine is one of the most powerful anti-histamines.

I did! As soon as I heard that i jotted it down in my notes.

I'd stay away from Finasteride
I had some horrible sides with palmetto
try maca - its just about the best thing I've tried; I've got hairs growing like mad on my temples
btw-apple cider vinegar has been a recent revelation

Apple cider vinegar internally or topically?

both
I've only been on it a few days and it's almost, like, 'cured' my itchiness, flakes and dermo flare ups
magic stuff

orwell wrote:I'd stay away from Finasteride
I had some horrible sides with palmetto
try maca - its just about the best thing I've tried; I've got hairs growing like mad on my temples
btw-apple cider vinegar has been a recent revelation

Hey Orwell - What Maca are you using?

scot, funny you should ask as I'm back on Now (brand) red maca after stupidly switching to gold/yellow organic. I had assumed the organic was, by nature, going to be perfect, but not so. My hair just wasn't responding as well to the organic yellow maca. My sex drive was way down also; I thought I was just being paranoid or something...but no, from what I've read it turns out maca red is far better for maintaining hair than yellow maca.

IH can you confirm this?

I want to re order Maca(I bought it once from a local pharmacy but they don't sell it anymore)
I have searched Iherb.com and swanson for Maca, there are tons of different stuff, different brands and different miligrams. Any suggestions on which one should I go for ?

To all you off-topic monsters I have one thing to say:

Why does some users of finasteride report INCREASED facial hair growth while others report the opposite reaction? Is this a proof of something?

Misirlou Immortal already addressed this on the first page.

In the minority, there are those who have a highly negative reaction to finasteride, such as "reflex hyperandrogenicity." This is where DHT is actually increased.

I know he mentioned it, but I still don't fully understand why this happens. But it is pretty obvious that playing around with hormones is like stealing money from the mob.

I use a pretty potent Maca grown at high elevations, just like the Incans originally used, known as "Imperial Gold Maca":

http://www.imperialgoldmaca.com/

I need to start taking two heaping teaspoons a day, but have been doing one lately. I've had the stuff for a while, but only recently started making it a regular occurrence. Now that orwell confessed that he's had temple regrowth from it...I'm DEFINITELY going to be making a point to take two teaspoons a day...

Nidhogge what do you mix the maca with? I dont see it being very soluble!

Just water man, it's gelatinized powder so it's pretty concentrated and mixes fairly well. Some of it gets sorta "jelly" and I just chew that and swallow it. If you mix it a bunch and let it sit for a few minute then mix it again, it'll go into solution pretty good.