Epitestosterone, premature balding, and "male PCOS"
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I don't know enough to be able to say how to fix male PCOS. Sorry.
As to injecting it: Epitestosterone is a controlled substance, treated by the government like steroids.
I think it's crazy how understudied it is! It's an active hormone produced alongside testosterone and we barely know anything about it. Its function in the body seems really unique and interesting - as far as I know it is the ONLY endogenous anti-androgen. In the Peater context of testosterone sometimes being a stress hormone, epiT sounds really relevant.
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I insufferable referenced this topic on
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Epitestosterone isn't even present on most charts of hormone production haha.
It appears that this is its main production pathway. (source)
DHEA is converted by 3 beta-HSD to androstenedione. (same pathway as testosterone's production from DHEA so far)
Then the enzyme 17alpha-hydroxysteroid dehydrogenase (17α-HSD) converts androstenedione to epitestosterone. (while testosterone's production pathway is that 17beta-HSD converts androstenedione to testosterone)
So whether your body makes testosterone or epitestosterone from androstenedione depends on which enzyme is used, 17alpha-HSD or 17beta-HSD.
17alpha-HSD is "inhibited by synthetic estrogens and 17beta-estradiol" (source)
According to the first study, 17alpha-HSD makes several other epimers too, including epiDHT, which seems to be even less known than epiT! Isn't it a big deal that such a hormone even exists? There seems to be a whole other half of hormone production going on? Perhaps there are even more that are completely unknown right now.
Like aromatase converts testosterone to estradiol (also known as 17beta-estradiol), there is a corresponding phenomenon with epitestosterone. Aromatase converts epitestosterone (also known as 17alpha-testosterone) to 17alpha-estradiol. (which I assume could be called epi-estradiol if you wanted)
According to the wikipedia article, 17alpha-estradiol has good effects: https://en.wikipedia.org/wiki/17α-Estradiol - 17alpha-estradiol is 100x weaker than "regular" estradiol. Perhaps its good effects are because it displaces estradiol?
17α-Estradiol "antagonizes the hypertrophic response of 17β-estradiol, probably by acting as an antiestrogen by virtue of its very low activity."
"Supplementation with 17α-Estradiol increases the median lifespan of male mice by 19%, while not affecting female lifespan. This treatment does not lead to feminization of male mice."
High testosterone production leads to a certain amount aromatizing to estradiol. But the body naturally produces epitestosterone too and this aromatizes to 17alpha-estradiol instead. So when the ratio of testosterone to epitestosterone production is imbalanced in favor of testosterone, I predict you would also imbalance the ratio of estradiol to 17alpha-estradiol in favor of estradiol. Probably has big effects.
Maybe this is why epitestosterone has been seen to have strong anti estrogen effects, despite not being an aromatase inhibitor.
I would expect that endocrine disruption does just as much damage to epitestosterone as to testosterone. A bit of evidence for that: Cadmium is a well known endocrine disruptor, and it's been seen in mice to suppress 17alpha-HSD. (source)
As a thought experiment, imagine four men. What would each type look like?
- High test, high epiT (this would have been the norm before endocrine disruption. Look at old pictures to see this type.)
- High test, low epiT (this is what TRT does to you since injecting increases testosterone without increasing epitestosterone. So you get high levels of test while still having hypogonadal levels of epitestosterone. So imagine the stereotypical TRT user here. Red face, bald, something weird going on.)
- Low test, high epiT (I'm not sure if this happens much. It wouldn't be a good thing, but I think it would be a different kind of dysfunction than we're used to seeing.)
- Low test, low epiT (this is a known type, it has been called "male PCOS" - he has insulin resistance and premature balding. I think he's the disastrous standard millennial male of today)
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Here's Danny Roddy's view on the high DHEA premature balders (no mention of epiT though)
Basically he says stress provokes prolactin which makes the adrenal glands produce more DHEA. The young bald men had 340-730 mcg/dl DHEAS, while the non-bald young men had 124-300 mcg/dl.
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@insufferable is it possible that epiT and elevated DHEA could go hand in hand?
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@risingfire They are indeed found together in the "male PCOS" condition.
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I don't totally understand this guy's work. He's one of the few talking about epiT.
"Flowers for Algernon: steroid dysgenesis,
epigenetics and brain disorders
Bryan K. Sanders"
http://if-pan.krakow.pl/pjp/pdf/2012/6_1285.pdfHe seems to be proposing something like this: Early life SSRI exposure causes autism because it inhibits epitestosterone in the brain.
"the role of epiT in brain development remains a long neglected area of research. [...] It is herein proposed that epiT deficiency disrupts the action of sex steroids and other hormones (e.g., glucocorticoids) at their target sites, and may trigger the expression, overexpression or downregulation of the myriad genes implicated in several brain disorders."
"inhibition of epiT synthesis in rats by either VPA exposure or a citalopram-induced increase in serum T or 17b-E2 during a critical period in brain development raises the question of whether epiT is the central mediator of the epigenetic regulation of gene expression. If so, endocrine disrupting agents that impair epiT synthesis may be the most important factors contributing to pervasive developmental disorders."
He also wrote this little thing about epiT:
https://pubmed.ncbi.nlm.nih.gov/17382481/
He conjectures there that androsterone and epitestosterone are very important. And that epiT may be lowered by stuff like ibuprofen or opiods and raised by "antimycotics that do not impair testosterone biosynthesis" (So salicylic acid - aspirin? Not sure how he comes to this conclusion as I can only see the abstract.)His idea about autism and epiT was tested just recently in this study. But it didn't find much. There wasn't much difference in urinary excretion of epitestosterone between normal kids and autistic kids.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931062/I think these researchers like the idea that epiT could be involved because they're trying to reconcile the "extreme male brain" theory of autism with the conflicting fact that male autistics aren't in any way high testosterone, and in fact the males show decreased masculinization. But epitestosterone could help explain that contradiction. I think that must be where these researchers are coming from.
I wouldn't draw any conclusions from urinary hormone excretion studies though. Does an increase in hormone excretion mean that tissue levels have increased, or does it mean that tissue levels are decreasing? As I understand it, either one can be true.
Here is a recent epitestosterone study.
https://pubmed.ncbi.nlm.nih.gov/28870779/
The abstract (all I can access) says that in rats, epiT by itself (without testosterone being present) is able to restore the proper masculinization of testicle weight and AGD (an important measure of physical masculinization) just like testosterone does. This is so interesting because epiT is an "anti-androgen" in other ways. -
I remember on RPF there was a thread where a guy got lab work after being on 6-Ketoprogesterone for a few weeks and his T:EpiT ratio shot up to 9:1
I receded a bunch when I experimented with 6keto, despite it being anti-cortisol so this theory does make a lot of sense IMO.
Anyone have a source for pine pollen with a positive EpiT:T ratio?
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Found this article which linked a study.
https://musclemonsters.com/blogs/blog/natures-newfound-anabolic-steroid-pine-pollen
"According to a pine pollen study conducted by The U.S. National Library of Medicine, one variety of Pine pollen known as Pinus Sylvestris contains 80ng/g of testosterone, 110ng/g of epitestosterone, and 590 ng/g of androstenedione…"
The study linked:
https://pubmed.ncbi.nlm.nih.gov/5549221/That's a good ratio, no? You want more epitestosterone than testosterone?
Looks like there's some supplements with Pinus sylvestris on Amazon/Google if you search "Pine pollen Pinus sylvestris".
You're telling me I can make muscle gains AND hair gains from one natural supplement? I am definitely gonna try this.
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@saturnuscv said in Epitestosterone, premature balding, and "male PCOS":
I remember on RPF there was a thread where a guy got lab work after being on 6-Ketoprogesterone for a few weeks and his T:EpiT ratio shot up to 9:1
I receded a bunch when I experimented with 6keto, despite it being anti-cortisol so this theory does make a lot of sense IMO.
Anyone have a source for pine pollen with a positive EpiT:T ratio?
Very interesting, thank you!
Found the thread I think: https://raypeatforum.com/community/threads/test-results-before-after-using-6-keto-p4.29137
@Hearthfire said in Epitestosterone, premature balding, and "male PCOS":
Found this article which linked a study.
https://musclemonsters.com/blogs/blog/natures-newfound-anabolic-steroid-pine-pollen
"According to a pine pollen study conducted by The U.S. National Library of Medicine, one variety of Pine pollen known as Pinus Sylvestris contains 80ng/g of testosterone, 110ng/g of epitestosterone, and 590 ng/g of androstenedione…"
The study linked:
https://pubmed.ncbi.nlm.nih.gov/5549221/That's a good ratio, no? You want more epitestosterone than testosterone?
Looks like there's some supplements with Pinus sylvestris on Amazon/Google if you search "Pine pollen Pinus sylvestris".
You're telling me I can make muscle gains AND hair gains from one natural supplement? I am definitely gonna try this.
I was thinking about pine pollen for epitestosterone. It would be interesting to apply it topically to a bald scalp. I'm not sure what would happen from taking it orally.
My concern with pine pollen for epiT is the high androstenedione content. This is the precursor to both testosterone and epitestosterone. If I remember correctly I saw some study on urine levels that sounded like exogenous androstenedione would raise testosterone more than epitestosterone.
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@insufferable have you ever tried spironolactone? It's used for women with PCOS. It's much easier to acquire compared to epiT
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@risingfire said in Epitestosterone, premature balding, and "male PCOS":
@insufferable have you ever tried spironolactone? It's used for women with PCOS. It's much easier to acquire compared to epiT
I'm not familiar with it, what does it do?
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This is the study that measured testosterone, epitestosterone, and DHT in the hair follicles of balding guys.
https://www.jidonline.org/article/S0022-202X(15)41116-9/fulltext
Here's the result:
What stands out most to me is plain old testosterone. Bald men have a lot more testosterone in their hair follicles. But as you know, they don't have any more testosterone in their blood than non-balders, and don't display the good "results" of testosterone in the body any more than non-balders. Anecdotally, I think they display a lot less! And at least in premature balders ("Male PCOS"), the studies confirm this.
It makes me think of calcium and vitamin K2. Calcium is good in the bones and bad when it inappropriately gets into soft tissue. Vitamin K2 somehow keeps calcium in the bone and out of soft tissue.
Some unknown factor puts testosterone where it should be and keeps it out of where it shouldn't be - the hair follicle. (and perhaps other places?)
When that unknown factor is not functioning well, testosterone is less present where it should be and more present where it shouldn't be.
Another question is what function do hormones have in hair follicles? What would testosterone be doing in your hair? What good does it think it's doing up there haha? Seems to me that it shouldn't be there at all. So WHY does it show up there?
Also I'd like to know how and why DHT has the function of miniaturizing hair in the first place. How does it do that? (I don't agree with the alternative claim that DHT doesn't cause hair loss. It absolutely does. DHT directly miniaturizes hair follicles right away in lab tests. However I do agree with the claim that DHT is good for you and that "high DHT men" often have plenty of hair. Because it's the varying levels in the different tissues that matter.) So how and why does DHT miniaturize hair? What purpose is it fulfilling, or attempting to fulfill but going off course instead?
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@insufferable That study theorizes that epitestosterone converting to epiDHT is what prevents hair loss. EpiDHT takes the seat of DHT in the hair follicle, thus preventing DHT from getting in and doing its thing.
There are two more studies in this series, which don't have quite as nice and clear results. I'll post them soon.
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@insufferable it was designed as a potassium sparing drug for high blood pressure, edema, pcos, heart failure and excess aldosterone. If I remember correctly, it's an anti-androgen
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@insufferable this is quite interesting.
EpiT is 5AR inhibitor. I wonder how useful it would be in taking if it could be acquired. Is it known to inhibit hpg axis?
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@risingfire I would imagine not. Most pharmaceutical anti-androgens (at least those that block the androgen receptor itself - for example bicalutamide) actually increase levels of circulating androgens because the hypothalamus androgen receptors are also "blocked" and as such the hypothalamus "thinks" that there are no androgens in serum.
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@saturnuscv thank you
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Supposedly you can increase epitestosterone by topically applying 7-keto-DHEA. I doubt applying it to the scalp would do anything, but if I can get the 7-keto-DHEA to dissolve, I'll put some on my scalp and on my navel/stomach and see what happens.
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@Gaston do keep us updated on that. I want to try 7kDHEA but I don’t want to make anything worse.
My hair is not too bad at the moment but since stopping progesterone I have been shedding more than usual. I’m close to just giving up on exogenous steroids and thyroid+cholesterol+bloomaxxing because every time I introduce some kind to steroid it either greatly aggravates shedding (Pansterone) or makes me feel and look like shite (Cortinon)
