Testosterone/Epitestosterone Ratio And Baldness

[PurpleHeart]

Hello everyone this is another thread about hair loss and well another day another theory.

My focus this time is on the ratio of Testosterone to Epitestosterone.

So here are some studies:

https://www.researchgate.net/public...uctase_as_Indicators_of_Male-Pattern_Baldness

Comparative studies on level of androgens in hair and plasma with premature male-pattern baldness. - PubMed - NCBI

There is clearly a higher ratio of T/EpiT in balding subjects.
I don't focus on dht so much as i think that epitestosterone is the main reason why dht goes haywire because epitestosterone is a potent 5-ar inhibitor.

study to prove:

Epitestosterone: a potential new antiandrogen. - PubMed - NCBI

One way that i found to increase the ratio in favor of EpiT is with 7-keto dhea.

study to prove:

Delayed effects of short-term transdermal application of 7-oxo-dehydroepiandrosterone on its metabolites, some hormonal steroids and relevant prote... - PubMed - NCBI

also 7-keto seems to be effective against stress and helpful for the thyroid.

Study :

[Effects of 7-oxo-DHEA treatment on the immunoreactivity of BALB/c mice subjected to chronic mild stress]. - PubMed - NCBI

It is well known that epitestosterone is high in young males and stabilizes at a ratio of 1:1
in healthy adults.

As we all know mpb usually starts in adulthood for what it's worth.

So there is not much more i can say beacause its very hard to find studies on EpiT
or ways to increase it etc.

Really wanna hear the thoughts of people who know more.

 

[lampofred]

It's probably associated with progesterone levels.

Since pregnenolone goes down either the DHEA or the progesterone pathway, adding in that version of DHEA might have reduced the need for pregnenolone to turn into DHEA, allowing for more progesterone to be produced, which is why both testosterone and estradiol went down. DHEA-like steroids also have an anti-cortisol action, which is another way they are good for hair. But supplementing DHEA directly is dangerous, since in a poor hormonal environment, it will turn into testosterone and estrogen.

In general 5ar activity increases as progesterone goes down. Progesterone is your body's main defense against estrogen, but if you don't have the energy/metabolism to produce enough progesterone, you start producing these back-up 5ar-derived steroids to protect against estrogen, which are powerful estrogen antagonists but come at a price such as loss of subtlety, loss of hair, etc.

 

[PurpleHeart]

It's probably associated with progesterone levels.

Since pregnenolone goes down either the DHEA or the progesterone pathway, adding in that version of DHEA might have reduced the need for pregnenolone to turn into DHEA, allowing for more progesterone to be produced, which is why both testosterone and estradiol went down. DHEA-like steroids also have an anti-cortisol action, which is another way they are good for hair. But supplementing DHEA directly is dangerous, since in a poor hormonal environment, it will turn into testosterone and estrogen.

In general 5ar activity increases as progesterone goes down. Progesterone is your body's main defense against estrogen, but if you don't have the energy/metabolism to produce enough progesterone, you start producing these back-up 5ar-derived steroids to protect against estrogen, which are powerful estrogen antagonists but come at a price such as loss of subtlety, loss of hair, etc.

17-keto dhea cannot turn into estrogen or testosterone actually i saw another study with dhea and dhea increased Testosterone not epitestosterone 17-keto dhea did the opposite.

 

[brix]

I’m taking 6 keto p4 from idealabs. Another member on the forum tested this ratio after taking 6 keto p4 for a while and his ratio was 9:1 in favor of T.

I’ll report back if I notice hair loss but I’m expecting the opposite.

 

[lampofred]

17-keto dhea cannot turn into estrogen or testosterone actually i saw another study with dhea and dhea increased Testosterone not epitestosterone 17-keto dhea did the opposite.

I should have worded this clearer, but yeah, that's why I said "that version of DHEA" when referring to the study. It's probably similar enough to regular DHEA to reduce the need for DHEA but different enough from DHEA that the enzymes that metabolize DHEA into testosterone and estrogen don't work on this version.

But I still don't think it's safe to supplement this, Peat says supplementing versions of preg/prog/dhea instead of the originals can have destabilizing effects in the long-run. And supplementing regular DHEA most likely won't work, since it will turn into testosterone/estrogen and actually accelerate baldness.

Are things like high dose caffeine, aspirin, high protein, high calcium to phosphate, fructose, Vit D + K + E, etc. to raise metabolism not working?

 

[johnwester130]

Hello everyone this is another thread about hair loss and well another day another theory.

My focus this time is on the ratio of Testosterone to Epitestosterone.

So here are some studies:

https://www.researchgate.net/public...uctase_as_Indicators_of_Male-Pattern_Baldness

Comparative studies on level of androgens in hair and plasma with premature male-pattern baldness. - PubMed - NCBI

There is clearly a higher ratio of T/EpiT in balding subjects.
I don't focus on dht so much as i think that epitestosterone is the main reason why dht goes haywire because epitestosterone is a potent 5-ar inhibitor.

study to prove:

Epitestosterone: a potential new antiandrogen. - PubMed - NCBI

One way that i found to increase the ratio in favor of EpiT is with 7-keto dhea.

study to prove:

Delayed effects of short-term transdermal application of 7-oxo-dehydroepiandrosterone on its metabolites, some hormonal steroids and relevant prote... - PubMed - NCBI

also 7-keto seems to be effective against stress and helpful for the thyroid.

Study :

[Effects of 7-oxo-DHEA treatment on the immunoreactivity of BALB/c mice subjected to chronic mild stress]. - PubMed - NCBI

It is well known that epitestosterone is high in young males and stabilizes at a ratio of 1:1
in healthy adults.

As we all know mpb usually starts in adulthood for what it's worth.

So there is not much more i can say beacause its very hard to find studies on EpiT
or ways to increase it etc.

Really wanna hear the thoughts of people who know more.

https://www.jidonline.org/article/S0022-202X(15)41116-9/pdf

The levels of epitestosterone were shown to be slightly differentbetween the balding group (mean 0.34 ng per g, p = 0.002, and0.44 ng per g, p < 0.001, fathers and their sons, respectively) and thenonbalding group (mean 0.41 ng per g and 0.67 ng per g,respectively) (Fig 1b).

 

[johnwester130]

. It can be presumed that the inhibition of 5a-reductase byepitestosterone is accompanied by reduction of the inhibitorepitestosterone to epidihydrotestosterone, contributing to anormalization of the hair growth cycle and a reversal of the hair-loss process (Fig 3).

 

[MyUsernameHere]

Oh that is really interesting. I'm amazed that in 8 years of researching hair loss I didn't see this study yet.

It seems that epitestosterone serves as a natural 'regulator' of 5-alpha reductase in those who do not lose their hair. The difference in the T/EpiT ratio of balding people is very striking, that is a major hormonal imbalance.

The difference between the fathers of the two groups was more clear - the T/E ratio of the balding fathers (mean 46.41, range 32.99±68.34, p < 0.001) was about five times that of the nonbalding fathers (9.17, 6.34±11.41).

Five times the difference, holy stuff! It's no wonder that our 5-AR activity is bonkers and the follicles are bathing in DHT when there is nothing there to put the brakes on. Now of course my first thought was that instead of inhibiting 5-AR, we should be looking at the pathway that creates this epitestosterone and why we might be deficient in it, but of course, we don't know ***t about that:

Epitestosterone is believed to form in a similar way to testosterone; a 1993 study found that around 50% of epitestosterone production in human males can be ascribed to the testis,[3] although the exact pathway of its formation is still the subject of research.

I would be interested in seeing the difference in serum as well.

 

[johnwester130]

Oh that is really interesting. I'm amazed that in 8 years of researching hair loss I didn't see this study yet.

It seems that epitestosterone serves as a natural 'regulator' of 5-alpha reductase in those who do not lose their hair. The difference in the T/EpiT ratio of balding people is very striking, that is a major hormonal imbalance.

The difference between the fathers of the two groups was more clear - the T/E ratio of the balding fathers (mean 46.41, range 32.99±68.34, p < 0.001) was about five times that of the nonbalding fathers (9.17, 6.34±11.41).

Five times the difference, holy stuff! It's no wonder that our 5-AR activity is bonkers and the follicles are bathing in DHT when there is nothing there to put the brakes on. Now of course my first thought was that instead of inhibiting 5-AR, we should be looking at the pathway that creates this epitestosterone and why we might be deficient in it, but of course, we don't know ***t about that:

Epitestosterone is believed to form in a similar way to testosterone; a 1993 study found that around 50% of epitestosterone production in human males can be ascribed to the testis,[3] although the exact pathway of its formation is still the subject of research.

I would be interested in seeing the difference in serum as well.

can a person take epitestosterone directly?

 

[MyUsernameHere]

can a person take epitestosterone directly?

It's not going to be that simple, if you can even get your hands on it.

First of all you have to consider whether this is a systemic imbalance or one local to the hair follicle. As far as I know the hair follicles do not synthesize their own testosterone, but obtain it via spillover from serum (someone correct me if I'm wrong). If epitestosterone is the same and its lack in hair follicles is reflective of the serum status, then we can assume that we have a rather wide systemic lack of epitestosterone in our entire body in which case supplementing it might make sense.

You have to consider that it is, in essence, an anti-androgen though, and it's questionable whether ingesting it orally would give adequate absorption and tissue distribution to ensure you don't get anti-androgenic side effects where you don't want them.

 

[lvysaur]

In general 5ar activity increases as progesterone goes down. Progesterone is your body's main defense against estrogen, but if you don't have the energy/metabolism to produce enough progesterone, you start producing these back-up 5ar-derived steroids to protect against estrogen

This is basically what I've always thought as well. Estrogen dominance through some avenue, excess DHT is created on-site in the tissue in compensation (aka 5ar upregulation). Lack of progesterone is one avenue of estrogen dominance. There are potentially infinitely many avenues, and most people experience multiple.

 

[Zigzag]

This is basically what I've always thought as well. Estrogen dominance through some avenue, excess DHT is created on-site in the tissue in compensation (aka 5ar upregulation). Lack of progesterone is one avenue of estrogen dominance. There are potentially infinitely many avenues, and most people experience multiple.

SO if we could effectively reduce estrogens (without side actions, not with aromasin), upregulate progesterone, DHT should go down itself?

 

[DhtAssassin]

SO if we could effectively reduce estrogens (without side actions, not with aromasin), upregulate progesterone, DHT should go down itself?

That theory is a joke. Just go to trans reddit page and look for people taking huge amount of estrogen - they regrow hair. I can't believe some people are still discussing that fact.

 

[MyUsernameHere]

This is the proposed pathway where epitestosterone is made[1](Ae-17a-diol aka 5-androstene-3b,17a-diol/7a-Hydroxytestosterone is the supposed precursor). You can see that progesterone can't fix this, and is not a good option for most men anyway. In my case it makes me moody and numbs my penis. Hardly acceptable. Not sure about 6-keto P4.

Additionally epitestosterone is used as a marker for doping and the acceptable ratio of testosterone to epitestosterone in urine is about 1 to 6[2]. If bald men's serum ratio was as screwed up as their hair, they would be immediately disqualified from most sports. That means that the ratio is probably OK in serum, but screwed up in the hair follicle.

I used to think that the hair follicle receives its testosterone from serum, but apparently that is not the case:

"Human pilosebaceous units possess enough enzymes to form the active androgens testosterone and dihydrotestosterone."[3]

That means that the hormonal pathways leading to epitestosterone are probably greatly silenced in the balding hair follicle and heavily favor the metabolism into testosterone and 5a-DHT, which is clearly detrimental to hair. Something is obviously going wrong downstream from pregnenolone so if you're going to apply something topically or supplement, preg would be a better choice. It's still likely far too upstream to work, may even make things worse by shunting most of it into T & DHT.

 

[JDreamer]

That theory is a joke. Just go to trans reddit page and look for people taking huge amount of estrogen - they regrow hair. I can't believe some people are still discussing that fact.

They're becoming women boss and they're usually taking frankenstein progestins right along with it. Tipping the axis over completely to the feminizing side is not the solution and does not discredit the role of estrogen in male hair loss.

 

[JDreamer]

This is basically what I've always thought as well. Estrogen dominance through some avenue, excess DHT is created on-site in the tissue in compensation (aka 5ar upregulation). Lack of progesterone is one avenue of estrogen dominance. There are potentially infinitely many avenues, and most people experience multiple.

After speaking with Dr. William Wong it was determined that the Epstein Barr Virus is another one of those "many avenues" for me - along with screwing with my thyroid.

 

[DhtAssassin]

They're becoming women boss and they're usually taking frankenstein progestins right along with it. Tipping the axis over completely to the feminizing side is not the solution and does not discredit the role of estrogen in male hair loss.

What progestins?
For example this one.
[MtF] 27 Years Old, ~1 Year HRT (You can regrow your hair!) : transtimelines
Took only estrogen for 8 months, then added spiro as I understand. He nuked his T, boosted his estrogen - insane regrowth.

I'm not saying that it's the way to go.. People who say that estrogen causes MPB are just in denial. Estrogen does reduce body/beard hair though. Scalp hair is different for some reason.

 

[JDreamer]

What progestins?
For example this one.
[MtF] 27 Years Old, ~1 Year HRT (You can regrow your hair!) : transtimelines
Took only estrogen for 8 months, then added spiro as I understand. He nuked his T, boosted his estrogen - insane regrowth.

I'm not saying that it's the way to go.. People who say that estrogen causes MPB are just in denial. Estrogen does reduce body/beard hair though. Scalp hair is different for some reason.

Spiro is a Frankenstein progestin and your interpretation of their regimen is off. They were taking Spiro from the very start in either the morning or at night. They also took oral estrogen for 8 months and then injections for the last 4 months. What this person is doing is literally creating conditions in their body that are similar to that of a healthy woman's hormone cycle because they're purposely going male-to-female. Women who's hormone cycles are screwed up from PCOS literally make too much estrogen and begin to lose their hair in similar fashion to MPB. Women in menopause start losing hair.

You're also failing to account for gonadal hormone productions vs. adrenal hormone production i.e. stress hormones. This has been routinely discussed on this forum over the last few months by bright minds like @mrchibbs, @Estradiol, etc etc. In fact the thread about the guy using birth control pills to regrow his hair (and Spiro too if I'm not mistaken) sort've ties into your link because OC pills suppress adrenal hormone activity. But he ended up feminized as well.

None of us are trying to feminize ourselves. We're trying to tip our bodies back into proper gonadal production which requires us to not be estrogen dominant males. Understand the difference? If you don't know the problems created by estrogen dominance use the search feature - there's plenty of info.

Btw I followed enough threads over on HairlossTalk that detailed when they took estrogen on its own. Initial results were great then they hit the massive wall and the sexual dysfunction started.

 

[MyUsernameHere]

I don't think that taking systemic anything is a good approach for male pattern baldness given that we see a whole lot of evidence that the dysfunction is limited to the hair follicle. The testosterone/epitestosterone ratio seems normal in serum (and other tissues as far as we know).

The questions we should be asking ourselves is why so much pregnenolone is going down the DHEA pathway into testosterone or rather why the other side of the pathway leading into 5-androstene-3b,17a-diol is underactive.

The OP study is actually hugely important - it has been known for a long time that in MPB follicles both 5-alpha reductase and the androgen receptor are overexpressed, but what hasn't really been known is 'why'. It's been speculated that this is due to SRD5A2 gene being overexpressed (the 'genetics' explanation) but the study that @PurpleHeart posted shows that the dysfunction is even further upstream. Since epitestosterone, a natural 'anti-androgen' and 5-AR inhibitor, acting as a sort of intrinsic brake on androgenic activity, is severely underproduced in these follicles, it makes perfect sense that the androgen receptor and 5-AR are upregulated being exposed to above normal levels of T & DHT (we know here that DHT upregulates its own production). The sad thing is there will probably be no further research on this angle but it amazes me that so far mainstream hair science has not connected the dots on this.

It also explains why mostly the only thing that works is people taking synthetic androgen receptor antagonists or 5-AR inhibitors. As this is a fundamental hormonal imbalance it can't be compensated for by things that force downstream effects, in much the same way that hypothyroidism can't be adequately compensated for by downing straight table sugar, this problem can't be compensated for by Minoxidil, or WNT agonists, or anything else that is being currently researched for hair loss (barring hair cloning, which is a way to sidestep the problem).

I think people here have a negative reaction to the connotation that DHT or androgens cause hair loss, and I would agree when we are talking about normal and physiological concentrations. But as we see here we are dealing with severely high androgens which are out of balance with their counterparts, and any hormone being out of balance (just like having too much T3, too much cortisol, aldosterone, or anything else) becomes bad and damaging in that context.

 

[mrchibbs]

Spiro is a Frankenstein progestin and your interpretation of their regimen is off. They were taking Spiro from the very start in either the morning or at night. They also took oral estrogen for 8 months and then injections for the last 4 months. What this person is doing is literally creating conditions in their body that are similar to that of a healthy woman's hormone cycle because they're purposely going male-to-female. Women who's hormone cycles are screwed up from PCOS literally make too much estrogen and begin to lose their hair in similar fashion to MPB. Women in menopause start losing hair.

You're also failing to account for gonadal hormone productions vs. adrenal hormone production i.e. stress hormones. This has been routinely discussed on this forum over the last few months by bright minds like @mrchibbs, @Estradiol, etc etc. In fact the thread about the guy using birth control pills to regrow his hair (and Spiro too if I'm not mistaken) sort've ties into your link because OC pills suppress adrenal hormone activity. But he ended up feminized as well.

None of us are trying to feminize ourselves. We're trying to tip our bodies back into proper gonadal production which requires us to not be estrogen dominant males. Understand the difference? If you don't know the problems created by estrogen dominance use the search feature - there's plenty of info.

Btw I followed enough threads over on HairlossTalk that detailed when they took estrogen on its own. Initial results were great then they hit the massive wall and the sexual dysfunction started.

Estradiol (E2) is basically a growth hormone. It causes cell division and renewal of biological processes. I think it can restart the hair growth cycle if it is stopped, but it can also stop it if it is ongoing. The problem is that in women, the spurts of high estradiol surges are balanced by the even higher levels of progesterone. So it isn't impossible that it causes initial improvements in hair growth, but in most cases that's not what happens. E2's physiological role is important in periodic cycles, but all the evidence is clear (at least to me), constant elevation of e2 leads to adverse pathologies.

I've seen the same accounts you have. Initial stimulation on E2, followed by hard collapse. I've seen several MtF cases of guys with perfect hair who end up losing their hair on E2 alone. And the real success stories always involved E2 + Spiro/CPA. The most amazing transitions even involve large doses of bioidentical progesterone (P4) taken rectally (to mimic the natural balance seen in women).

Bottomline, it always depends on the initial physiological state of the person transitioning. But considering we've seen accounts of full regrowth of bald scalps on spironolactone and cyproterone acetate alone (both which measurably suppress estradiol), I think we can say that it isn't E2 which is therapeutic.

I enjoy reading the transgender threads on reddit. There's so much information we can glean from these experiments.