Equol: A Natural Dht Binder And The Primary Ingredient In Brotzu

IdealForehead

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Since I've recently learned about Equol, I have been blown away that more people have not already tried to use it in their hair or in commercial formulations for hair. It really seems like a very promising compound.

What is Equol?
Equol is a natural compound which is made by bacteria in your gut after you eat soy products. It's generally considered to be good for health, and may be part of the reason Japanese people have lower rates of prostate cancer (as they eat much more soy and have more of the bacteria that can make equol from soy). (ref)

Equol is known as a "chiral" compound, meaning that it has a specific 3D structure which can present itself in one of two ways that are mirror images of each other. When a structure is chiral like this, the two mirror images are called enantiometers, and we call one "R" or "+" and the other "S" or "-".

The structures of the two versions are shown here:

A-Effects-of-100nM-17b-estradiol-R-equol-and-S-equol-on-ROS-accumulation-in.jpg


In R-equol, that one chemical bond that is bolded can be thought of as coming "out of the page" as you go from left to right. In S-equol, that same bond that is dotted can be thought of going "into the page".

So there are actually three types of equol that can exist:

1) R-equol
2) S-equol
3) Racemic equol ("racemic" means it contains a roughly equal mix of the R and S enantiomers)

In nature, when we consume soy, bacteria in our intestines will only create S-equol. Brotzu plans to use S-equol only. But on the chemical market (ie. Alibaba), all the equol I have encountered is sold as a racemic mixture. As we will see, this may not actually be a bad thing, as R-equol has some very unique properties which may be positive as well. In some ways it appears much stronger than S-equol.

Mechanisms of Action
Equol has several mechanisms of action that are known which are very relevant to the interests of hair loss, and some that may be relevant to maintaining general good health.

1) DHT binder
Equol binds directly to DHT. Once DHT is bound to equol, it can no longer bind to the androgen receptor. This means Equol essentially renders DHT inert. (ref)

This has obvious applicability to hair. Finasteride is used to reduce DHT by blocking its production, but finasteride is a messy drug which affects numerous other hormonal pathways in the process. Usually finasteride can reduce scalp DHT by ~60%.

Soaking your scalp in equol could accomplish a similar goal. Rather than stopping DHT from being made, it will just stop DHT from binding to your hair follicles, which accomplishes the same outcome but in a much simpler way. In theory, adding equol could increase the success rate of almost any anti-androgenic approach, or it could be a very good approach to use all by itself.

Very helpfully, both S-equol and R-equol bind equally to DHT, so it does not matter what formulation or type of equol is used to get this effect. R-equol, S-equol, or racemic equol should all do equally well. (ref)

2) ER-beta agonism
There are two estrogen receptors - ER-alpha & ER-beta. You can read more about these here. In short, from current knowledge, it appears ER-beta is likely the estrogen receptor we would ideally like to stimulate for both hair and prostate benefits.

R-equol can bind to both ER-alpha and ER-beta but only very weakly for both. S-equol has pretty good binding capacity for ER-beta and almost none for ER-alpha.

ER-beta agonism is desirable in part because it can actually work to reduce androgen receptor expression. (ref). This again accomplishes a major goal we want. With fewer androgen receptors on our scalp, our hair could theoretically become less sensitive to any testosterone or DHT that is circulating in the area.

The ER-beta agonism benefit is only significantly provided by S-equol though, not R-equol. Racemic equol will provide the ER-beta agonism benefit but at a reduced amount (since only the S-equol in the mixture will do what we want here).

Since pure S-equol is hard to get, if you are looking for cheap and readily available pure ER-beta agonism, it is much easier to accomplish with genistein, which is cheaply available here and discussed more in the estrogen thread.

3) Other effects
Equol has also exerted many other positive effects in studies. These effects can be differential between R-equol & S-equol, suggesting they may both have useful properties for the body.

In one rat study:
- R-equol reduced prostate size dramatically better than S-equol. This was surprising as both types of equol bind DHT equally, and S-equol is the one with better ER-beta agonism, which is known to help prostates. The researchers did not seems to know why R-equol was so much more effective in reducing prostate size, but it might be due to the fact that R-equol is known to be much more anti-oxidative and cytoprotective.
- R-equol also dramatically reduced white (undesirable) body fat compared to S-equol. R-equol is therefore thought to have positive metabolic effects for the general body.
- R-equol reduced anxiety of the rats when they had to run mazes.

Those researchers summarized the effects of equol overall as follows:

nutritionalhealth-foodscience77-g003.gif
(ref)

That article noted that in a skin study: "the R-equol and Racemic equol treatments were, in general, significantly more effective in improving human skin gene expression compared to S-equol". (ref)

So R-equol may have many benefits over S-equol (for prostates, skin, mood, anxiety, and body fat), but how exactly R-equol works differently from S-equol to enact all these extra benefits is not known.

Which Formulation is Best?
This then gives some ambiguity about which type of equol is actually the most desirable.

Both will bind equally to DHT. However, R-equol can provoke a much more powerful anti-prostate hypertrophy effect than S-equol for reasons unknown. Without knowing how R-equol does this, it's only speculation. But generally agents that work well for reducing prostate size (eg. finasteride & dutasteride) have also worked well for stopping androgenic hair loss. So maybe the R-equol would be more helpful for hair also.

Brotzu has decided to use only S-equol. This will provide the DHT binding and ER-beta agonism benefits of equol. But it won't provide any of the metabolic benefits, anti-prostate growth, or mood/anxiety benefits of R-equol. That may be irrelevant to some. Or it may be very relevant.

Debating too much about which enantiomer is best may be irrelevant altogether, as every source I have contacted on Alibaba has only had racemic equol, even when they are listing it as S-equol.

For my own part, I debated contacting Luo and asking him perform a chiral separation so I could get some pure S-equol. But the more I debated it, the more I figured why bother? R-equol may be just as good or better than S-equol. I wouldn't complain if my body fat (or anxiety...) went down a bit! Perhaps it is best to just get the racemic mixture, which is commonly available, and take advantage of both enantiomers.

One funny quirk of racemic equol is that when taken orally, it absorbs slower than either enantiomer does by itself. It still absorbs eventually and fully, but not as rapidly. (ref) In topical use, racemic equol was found to absorb well into the skin, work strongly within the skin cells, and create a "skin reservoir" with repeated application, which is very desirable. (ref)

Sources

The only reliable-seeming source I have found on Alibaba willing to do small orders is this one (https://nutrabiotech.en.alibaba.com). They do not manufacture equol but claim to manufacture other chemicals (SARMS). For equol, they state they are a reseller.

They quoted me:
10g $50 + shipping $45
30g $100 + shipping $45
100g $180 + shipping $45

Again this is for racemic equol, as that seems to be the only type which is commonly available without custom lab processing to separate the R's from the S's. I am in the process of finalizing my order for 30 grams, shipped by ePacket (skips nasty private courier brokerage fees and is very fast). I will test the sample upon arrival and post back what I find.

Dosing
We can easily come up with some general ideas for dosing from the many studies in humans that have now been done on equol, primarily for prostates or menopause.
  • In 70-80 kg men a daily dose of 12 mg per day was sufficient to significantly decrease symptoms of benign prostatic hyperplasia. (ref)
  • In one study of postmenopausal Japanese women, s-equol was tested at a dose of 10–30 mg/d. (ref)
  • Typical average intake of total soy isoflavones is ≈25–50 mg, of which ≈50% usually represents daidzin or daidzein—the precursors to equol. (ref)
Different sources seem to list broadly different solubilities for equol in ethanol from 15 mg/mL up to 200 mg/mL. Equol is nonwater soluble. I can find no data on propylene glycol solubility, but I expect it should be at least decent. Based on that info, there should be at a minimum no trouble getting 1% equol into any standard minoxidil solution like Kirkland or a custom base of 50% PG, 30% Ethanol, 20% water, which is what I typically use.

At 2 mL at bed and 1 mL in the morning (my standard topical approach), 1% equol would mean daily administration of 30 mg equol. In the radioactive minoxidil study, only half of the minoxidil applied to the scalp actually absorbed. (ref) If we presume half of equol will similarly absorb, this would be a very moderate dose right within the normal range of doses specified above. Only it should all be focused at least initially at the scalp to provide a more powerful localized effect.

I think this is a reasonable dose to start with, as even if it all goes systemic, there shouldn't be much risk of toxicity. We know S-equol is completely natural and we are all exposed to at least a bit in our diet. But R-equol is completely unnatural (doesn't get made in nature) so who knows what negative effects it might have over time?

As usual, with any experimental therapy, use at your own risk. There is no safety data or dosing data and there is no guarantee any chemical you order on the Internet will even be what its supposed to be.

Bottom Line
For those dying to get the benefits of Brotzu, I would guess equol is going to be likely responsible for 60-70% of any benefit Brotzu provides. Brotzu's formulation has the extra benefit of liposomes. But there should be no actual NEED for liposomes. Liposomes can help to improve the localization of effect to the hair follicles. But equol should absorb easily through the skin and into the scalp and hair even without liposomes, just like minoxidil or estrogen creams, etc.

For my own part, I have always preferred to mix my own chemicals when I can as it gives me absolute flexibility and control. So for my own part, I don't plan to wait. I think equol sounds like a great idea so I'm giving it a try.
 
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IdealForehead

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Awesome post as usual @IdealForehead . When do you think you'll start using ?

Thanks, and as soon as it arrives! Probably within 1 month giving time for shipping and then dropping off a sample at the lab for testing. I'm hoping it might allow me to safely reduce my daro dose a bit while also providing some general health benefits. We'll see.
 

Ollie

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Thanks, and as soon as it arrives! Probably within 1 month giving time for shipping and then dropping off a sample at the lab for testing. I'm hoping it might allow me to safely reduce my daro dose a bit while also providing some general health benefits. We'll see.

Are there any metrics that can compare potentency / effectiveness against other topical such as Ru ? I presume not as both mechanism are slightly different ?
 

IdealForehead

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Are there any metrics that can compare potentency / effectiveness against other topical such as Ru ? I presume not as both mechanism are slightly different ?

Unfortunately it would be impossible to know for the reason you said. They all have very different mechanisms of action and Equol is completely unique.

To review:
  • RU, daro, flutamide, cypro, and spironolactone are androgen receptor antagonists - they bind to the androgen receptor so that androgens can't bind to it.
  • Finasteride & dutasteride are 5-alpha reductase inhibitors - they bind to the 5-AR enzyme to shut down production of DHT (as well as numerous other hormones).
  • Equol binds directly to DHT, so that once it is stuck to DHT, DHT can't bind the androgen receptor. Equol also has a lot of other good mechanisms of action like ER-beta agonism that can reduce the number of androgen receptors being made. But this is all less well understood.
I think it's very promising to note that in one study, 6 mg of equol orally twice a day was enough to fix most men's enlarged prostate symptoms within 4 weeks. This would suggest 6 mg twice a day might have effectiveness on par with finasteride or dutasteride, at least when it comes to prostates.

We don't know how perfectly this effectiveness on prostates should translate to hair protection, but I would bet based on the fact that we know prostates and hair loss are very closely linked it would be on par.

Of note, in the human prostate study, they used a "propriety R/S blend" but don't tell us what the blend was, so all we know is it wasn't completely R-equol or completely S-equol but some sort of mixture. (ref) So obviously they saw some special benefit to using both the R & S forms together.
 

zigzag

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Oh man, nice little research you did there. I'm gonna ask my chemist girlfriend to check this out as well. I bet she doesn't want a cue ball :D

BTW. What would be side effects of it? Different mechanism but still DHT is rendered useless if I read it correctly.
 
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whatevr

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Unfortunately it would be impossible to know for the reason you said. They all have very different mechanisms of action and Equol is completely unique.

To review:
  • RU, daro, flutamide, cypro, and spironolactone are androgen receptor antagonists - they bind to the androgen receptor so that androgens can't bind to it.
  • Finasteride & dutasteride are 5-alpha reductase inhibitors - they bind to the 5-AR enzyme to shut down production of DHT (as well as numerous other hormones).
  • Equol binds directly to DHT, so that once it is stuck to DHT, DHT can't bind the androgen receptor. Equol also has a lot of other good mechanisms of action like ER-beta agonism that can reduce the number of androgen receptors being made. But this is all less well understood.
I think it's very promising to note that in one study, 6 mg of equol orally twice a day was enough to fix most men's enlarged prostate symptoms within 4 weeks. This would suggest 6 mg twice a day might have effectiveness on par with finasteride or dutasteride, at least when it comes to prostates.

We don't know how perfectly this effectiveness on prostates should translate to hair protection, but I would bet based on the fact that we know prostates and hair loss are very closely linked it would be on par.

Of note, in the human prostate study, they used a "propriety R/S blend" but don't tell us what the blend was, so all we know is it wasn't completely R-equol or completely S-equol but some sort of mixture. (ref) So obviously they saw some special benefit to using both the R & S forms together.

I do remember there being some discussion here on the forums about a certain isomer of S-Equol being the one we want and the other not doing something or another (either binding to DHT or stimulating ER-ß). And I think the main issue with Equol was that it was too expensive to obtain in quantities that would be useful, so I'm hoping Brotzu has economies of scale going in his favor. Some members here tried those japanese Equelle tablets orally with no effect. I would suppose the topical dose would be far less than the oral one. If 6 mg works for the prostate then topically it would supposedly be good enough for the hair as well.

On a side note I tried getting some Genistein from Lotioncrafter, but the idiots there did not respond to two of my e-mails inquiring about whether or not they would ship to my country (it's not on the list yet they ship to neighboring countries). I think I'm done with them. Anyone know another good source that isn't China ?
 

17AndBalding

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Great thread! Made me more hopeful for Brotzu, can't wait till next week!
 

Armando Jose

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I do remember there being some discussion here on the forums about a certain isomer of S-Equol being the one we want and the other not doing something or another (either binding to DHT or stimulating ER-ß)
Me too, even in alt.sci-baldspot
 

IdealForehead

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I have done some more reading and research on the subject of which version (R, S, or racemic) of equol would be most ideal for treatment of hair loss, and come up with some fascinating results.

The primary reason Brotzu is using S-equol is almost certainly the same reason they are using DGLA instead of PGE1. S-equol is a completely natural dietary product. So is DGLA. By using these "natural dietary products", they completely escape any significant regulation, and get to release their product as a "natural health product". This saves an enormous amount of money on testing for safety or efficacy.

But if we want to look at the question of what is truly best on a deeper level than that, we need to review the evidence again.

First of all, we should review again that in the rat prostate study comparing all three, only R-equol led to a significant decrease in prostate size. S-equol did not cause any significant change in prostate size.

We also have a very good skin study (ref) comparing all three which showed again that for skin purposes, R-equol was much more potent in almost every way. This included the following effects, of which one in particular was an absolute shock to me when I saw it, and likely completely explains the difference in prostate activity of both equol forms:
  • Overall, 16 genes were more powerfully regulated by R-equol, while only 3 genes were more powerfully regulated by S-equol.
  • Genes for collagen production, elastin production, and production of a skin breakdown inhibitor were all much more strongly activated by R-equol than S-equol.
  • Genes for three proteinases which break down skin during age were significantly more inhibited by R-equol compared with S-equol.
  • The gene for making the 5-alpha reductase (type 1) enzyme was significantly inhibited by R-equol, but not S-equol.
This finding of R-equol decreasing 5-AR (type 1) expression is mindblowing to me, because we have no other agent that I am aware of that does this, and it completely explains how equol is so good at controlling prostate problems. Given that both R-equol and S-equol bind equally to DHT, if the DHT binding effect was the primary mechanism of action, we would expect both forms to be effective at reducing prostate size. However, only R-equol has been shown to have a significant effect on prostate size.

The fact that R-equol has this unique ability, and that R-equol, not S-equol, is the type of equol proven to reduce prostate volume suggests that: this is likely a big portion of the mechanism of action by which equol works (though not everything), and just like with prostates, we should expect S-equol to be much less effective for hair.

We can get some clues as to how important this 5-AR effect is from the human prostate study, where men were treated with a mix of R/S-equol. In the men with the largest prostates, a significant decrease in DHT levels was observed. But notably, no decrease in DHT was seen in most men overall, despite their prostate symptoms improving. This suggests that the mechanism of action for equol overall in this study was probably a combination of the DHT binding effect (which does not change hormone levels) and the decrease in 5-AR expression (which does change hormone levels).

This represents a completely new mechanism of action, which I will add to my original post.

For reference, here is a table of some skin genes affected by S-equol, R-equol, and racemic equol and their differing effects:

iphb_a_793720_f0004_b.jpeg


This makes R-equol actually very similar to finasteride/dutasteride in effect, but it is slightly unique compared to both. There are three types of 5-alpha reductase enzymes which convert testosterone into DHT - type 1, 2 and 3. Finasteride works by blocking 5-alpha reductase (type 2&3) from converting testosterone to DHT. Dutasteride works by blocking all three types of 5-AR.

R-equol accomplishes essentially the same thing by decreasing the amount of 5-alpha reductase (type 1) enzyme that is made in the tissues exposed to it. With less enzyme, less DHT will be made in the same fashion. We don't know if R-equol also reduces expression of 5-AR type 2 or 3 as well, as they weren't studied. Either way, this provides a very plausible mechanism for high effectiveness in stopping hair loss if racemic equol is used topically.

Unfortunately, this also suggests that people who have been sensitive to DHT-related (finasteride/dutasteride) side effects might be sensitive to the same side effects from R-equol if it goes systemic to any significant extent. Some people have claimed decreased finasteride side effects from topical administration. So perhaps the effect of equol could be similarly localized.

Equol has so many mechanisms of action that are completely unique. This is yet another and probably the most important (along with the DHT binding capacity). But it also goes to show, there is nothing for free in this world. Dealing with the androgen problem of male pattern baldness will always be a compromise regardless of how you choose to attack it. I think it's a matter of finding the approach that best suits each individual, and that unfortunately can usually only be determined through trial and error.

Overall I think this very clearly shows that racemic equol will be far more powerful for hair loss than S-equol (what is being used in Brotzu). If Brotzu is proven to work, it might represent a "cleaner" mechanism of action, as S-equol will work only by binding DHT and stimulating ER-beta to reduce androgen receptors.

However, whatever benefit S-equol (Brotzu) might provide, racemic equol will undoubtedly provide a dramatically more potent effect in the treatment of male pattern baldness, due to its ability to reduce expression of the 5-alpha reductase enzyme.
 
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Georgie

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S-equol has been tried. There was a guy here on this very forum who reproduced brotzu's lotion from the patent. That said, he did not use pure S-equol, but a japanese capsule form that i don't believe is entirely equivalent. Also, i don't think anyone has really given it enough of a go to judge efficacy. I think what needs to be taken into account is appropriate topical delivery via optimal vehicle, and whether or not on it's own it is effective. In theory yes, it looks to be a great treatment option. But so do many other treatments now proven to be for the most part useless. Not being a naysayer here. Just wanted to point out that it has been considered and tried before. I hope you find success with it though @IdealForehead . Given your positive responses to other treatments, I'm sure you will. Whether or not it works for the freak pack is another matter.
 

Georgie

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Interesting.

The aromatase enzyme catalyzes the conversion of androgens to estrogens in many human tissues. Estrogens are known to stimulate cellular proliferation associated with certain cancers and protect against adverse symptoms during the peri- and postmenopausal intervals. Phytoestrogens are a group of plant derived naturally occurring compounds that have chemical structures similar to estrogen. Since phytoestrogens are known to be constituents of animal/human food sources, these compounds have received increased research attention. Phytoestrogens may contribute to decreased cancer risk by the inhibition of aromatase enzyme activity and CYP19 gene expression in human tissues. This review covers (a) the aromatase enzyme (historical descriptions on function, activity, and gene characteristics), (b) phytoestrogens in their classifications and applications to human health, and (c) a chronological coverage of aromatase activity modulated by phytoestrogens from the early 1980s to 2015. In general, phytoestrogens act as aromatase inhibitors by (a) decreasing aromatase gene expression, (b) inhibiting the aromatase enzyme itself, or (c) in some cases acting at both levels of regulation.

In the late 1990s, premenopausal women were fed soy isoflavones for approximately 100 days and urine samples were collected to quantify estrogen excretion levels [75]. This last study demonstrated that soy isoflavone consumption may exert cancer-preventive effects by decreasing estrogen synthesis presumably by altering aromatase enzyme activity based upon previously published reports [75]. Finally several synthetic flavones were found to inhibit the aromatization of androstenedione to estrone using human placental micro- somes

Investigators using MCF-7 cells showed that mam- malian lignans (enterolactone and enterodiol) and genistein decreased aromatase enzyme activity
http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.781.8210&rep=rep1&type=pdf
 

Georgie

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Just to add the to above post, it does state that inhibition of aromatase/estrogen synthesis can be dose-dependant, that is, the higher the dose, the less inhibition.
 

Georgie

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Genistein itself can also interfere with the PG pathway by inhibiting both COX-2expression and activity, as well as by inhibiting EP and FP prostaglandin receptors, leading to reduced biological activity of PGE2.
 

whatevr

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I'm glad Brotzu chose S-Equol over R-Equol if R-Equol messes with 5-AR. Sure you could say that it will only be localized to the scalp, but a small part of it will almost certainly go into the rest of the body including the brain and then you have Finasteride #2. For those of us who already went through that and are trying to recover our hormones, no thanks. I also don't particularly care for any of the other effects of Equol and do not want it messing with other parts of my body. Pure and clean DHT down and ER-ß up in the scalp is the only thing I'm after. I'm sure the majority will think the same (especially ex-finasteride users).

If someone wants to go hardcore they can mix R-Equol themselves, but for me the main selling point of this topical is efficiency without side effects.

I don't think Equol was given a fair shake thus far. A few people just fucked around with some underdosed pills orally. Maybe someone tried making a topical but I don't put much faith that it was done right. At the very least you're supposed to make a topical from a clean powder, and not pills full of fillers and god knows what else.

However I don't think you need any kind of special liposomes to transfer equol through the skin. It's VERY soluble in ethanol, more than good enough for a topical, and should easily go across the skin. It's actually a surprisingly easy thing to try, I'm surprised no one did a proper trial in all this time. So much for the resourcefulness of HairLossTalk.com members throughout the years. Well, we will be waiting for @IdealForehead 's results.
 

whatevr

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That sh*t was an oral capsule of 10 mg per day. WAY more would be necessary orally than what they put in that product, because it gets distributed and lost throughout the body. Topically, likely a few mg's should be enough to achieve the desired effect. So, that isn't really a proper comparison. Why would you want to take equol orally anyway to bind up DHT all over your body when you only want that to happen in your hair follicles? That product was a failure from the get-go, but since the team behind it probably didn't have the know how to make a proper topical product they just stuck it into some gelatin capsules. No wonder it failed so hard and so fast.
 

dermrafok

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Extracted from one of the latest studies of the side effects of Propecia. x1000 times again.
Persistent neurological effects from other drugs are well recognized, such as tardive dyskinesia related to the use of phenothiazines for treatment of chronic schizophrenia. There is increasing scientific evidence from studies in rodents that finasteride may reduce the concentration of several neuroactive steroids important for neurogenesis and neuronal survival. An important neurosteroid is allopregnanolone (ALLO), a metabolite of dihydroprogesterone. ALLO is a potent ligand of the inhibitory GABA‐barbiturate receptor. GABAA receptors have variable sensitivities to ALLO in the settings of neurosteroid withdrawal, stress, social isolation and ageing. Less ALLO as a consequence of finasteride treatment could alter GABAergic transmission with implications for neuronal progenitors and young neurons. Interestingly, the mechanisms of irreversible phenothiazine‐induced tardive dyskinesia may be similar to the mechanisms underlying the persistent side effects of finasteride: in rats treated with the phenothiazine haloperidol to induce orofacial dyskinesias, co‐administration of progesterone prevented this side effect, while pretreatment of the rats with finasteride reversed this protective effect, demonstrating an important role of the progesterone pathway and its metabolites.4
 

IdealForehead

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Extracted from one of the latest studies of the side effects of Propecia. x1000 times again.
Persistent neurological effects from other drugs are well recognized, such as tardive dyskinesia related to the use of phenothiazines for treatment of chronic schizophrenia. There is increasing scientific evidence from studies in rodents that finasteride may reduce the concentration of several neuroactive steroids important for neurogenesis and neuronal survival. An important neurosteroid is allopregnanolone (ALLO), a metabolite of dihydroprogesterone. ALLO is a potent ligand of the inhibitory GABA‐barbiturate receptor. GABAA receptors have variable sensitivities to ALLO in the settings of neurosteroid withdrawal, stress, social isolation and ageing. Less ALLO as a consequence of finasteride treatment could alter GABAergic transmission with implications for neuronal progenitors and young neurons. Interestingly, the mechanisms of irreversible phenothiazine‐induced tardive dyskinesia may be similar to the mechanisms underlying the persistent side effects of finasteride: in rats treated with the phenothiazine haloperidol to induce orofacial dyskinesias, co‐administration of progesterone prevented this side effect, while pretreatment of the rats with finasteride reversed this protective effect, demonstrating an important role of the progesterone pathway and its metabolites.4

Jesus oh f***. Maybe I dont want R-equol either! lol.

This is why I love my beloved daro. Virtually none crosses the blood-brain barrier so at the tiny topical doses I'm using I don't think I have to worry too much about these crazy brain effects of other broader acting drugs.

The caveat to what you're posting is to still keep in mind we know there are people born with 5 alpha reductase deficiencies and they do not develop any major cognitive problems that I'm aware of. Now one may argue that developing with exposure to 5-ar and then losing it later in life is different from never having 5-ar at all.

But it is still at least somewhat reassuring that those completely deficient in 5-ar aren't developing dementia in their 30s or anything scary like that.
 
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