Why Endometriosis Is Extraordinarily Rare in Healthy 46,XY Males

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Full transcript of the original video, lightly edited for readability.

Men cannot get endometriosis. Hi, I'm John, founder of ENDOLLS, the only company that seems to be truly questioning the dogma behind endometriosis. So my statement men cannot get endometriosis is most likely going to irritate some people, but if you're not willing to look at the science from a non biased perspective, you're going to do more harm than good. So why do people say this? Because they're trying to get clicks and views. Me? Well, I hate misinformation. Because if we actually care about women with endometriosis, we need to follow the biology wherever it goes.

So if anything, there's one question that deserves much more attention than no one has asked. Why do healthy biological males almost never develop endometriosis? So first, let's start with the obvious. Yes, there are extraordinarily rare case reports in 46 X y males, but those cases are useful because they help us identify the biological barriers that normally make this disease incredibly difficult to establish. And that matters because? Instead of only asking how do we suppress endometriosis? We should also ask what does normal male biology do that makes endometriosis so hard to sustain?

Then reverse engineer those mechanisms for women. Because endometriosis is not just too much estrogen. An established lesion changes its receptor profile, its epigenetics, its steroid metabolism, its inflammatory signaling, its immune behavior, its apoptosis resistance, and even its ability to build blood supply. One major shift is progesterone resistance. Got a 2. Signaling falls got A 6 rises, progesterone receptor B becomes reduced, and the lesion loses normal progesterone responsiveness. At the same time, estrogen signaling becomes exaggerated. ER-beta can become highly overexpressed. SF-1 becomes active.

SF-1 drives C Y P 1 9 A one or aromatase. Aromatase converts androgens into estrogens. H S D 1 seven B one helps convert estrogen into potent estradiol, while H S D 1 7 B two, which helps inactivate estradiol, becomes inadequate. Then inflammation feeds it. COX-2 creates PGE2. PGE2 stimulates SF-1. Aromatase drives estrogen. Estrogen feeds more inflammatory and survival signaling. So you get this loop. COX-2, PGE2, SF-1, aromatase, estrogen, E R. Signaling. And right back into inflammation. Now compare that to a healthy male.

The first protective barrier happens before birth. SRY activates SOX9. SOX9 drives Sertoli cell development. Sertoli cells produce anti malaria hormone. AMH binds AMHR2, and the malaria ducks regress. That means normal male development removes most of the anatomical substrate associated with ordinary endometriosis. No uterus, no functional endometrium, no menstruation, no fallopian tubes, no ovaries, no ovarian estrogen cycle. That alone is a massive barrier. But the second barrier is the androgen system. Testosterone can go two major directions. Through C Y P1 9 A one, it can become estradiol or through 5 Alpha reductases SRD5A1 and SRD5A2.

It becomes DHT, and DHT. Cannot be aromatized into estrogen. That means 5 alpha reductase does more than create a stronger androgen. It diverts testosterone away from estrogen production. Then DHT. Strongly activates the androgen receptor. Women do have androgen receptors including an endometrial and endometriotic tissue. So the difference is not presence versus absence, the difference is exposure and signaling context. Healthy males exist in a much more androgen dominant environment with far more testosterone, DHT, androgen receptor occupancy, and lifelong androgenic programming. But DHT.

Has another pathway. DHT. Can become three beta deal and three beta dial can activate estrogen receptor beta. That is extremely important because now the male steroid environment can produce two signaling arms DHT. To androgen receptor and DHT. To 3 beta dial to ER-beta. And ER-beta is not just an on off switch. Different ligands can stabilize different receptor confirmations. That means estradiol bound to ER-beta may not produce the same downstream effect as 3 beta dial bound to ER-beta in other tissues. 3 beta dial and ER-beta signalling have been associated with anti migratory anti inflammatory differentiation supporting effects and suppression of pathways involving NF-kappa B COX-2, HIF-1 alpha VEGF, and EMT like behaviour.

Now look at what endometriosis needs. NF-kappa B COX-2 PGE2 HIF-1 alpha VEGF. In short, 3 beta dial has the potential to activate ER-beta in a manner that it becomes almost like an off switch. That means no more migration, invasion, inflammation, survival. There is a striking overlap in opposite directions. That does not prove three beta dial cures endometriosis. It means there is a legitimate mechanistic hypothesis that the male DHT. To 3 beta dial pathway may place anti disease pressure on an ER-beta dominant lesion.

Because remember, estrogen receptor beta is overexpressed in endometriotic lesions. And this leads to another question. Where does testosterone go inside an endometriotic lesion? Toward aromatase and estradiol or toward 5 alpha reductase and DHT? Because once testosterone becomes DHT, it is removed from the aromatizable pool. Then DHT can activate AR or become 3 beta diol and influence ER-beta. So endometriosis may not only involve excessive estrogen, it may also involve pathological steroid routing. Now add the other male barriers. No ovarian cycling, no menstruation, no repeated pelvic exposure to hemoglobin, heme and iron.

That matters because iron can drive reactive oxygen species, inflammatory signaling, macrophage dysfunction, fibrosis and tissue remodeling. So put the entire male Protection system together. SRY, SOX9, AMH, AMHR2, malaria and regression. No uterus, no menstruation, no ovaries, high testosterone, 5 alpha reductase, DHT, strong AR. Signaling, DHT. To 3 beta dial to ER-beta, and no recurring iron loaded menstrual environment. That is not one protective mechanism. That is a wall of biological barriers. Now ask the obvious question. If endometriosis occurred naturally in healthy males, where are the cases?

This is my long held statement. Even if you surgically placed endometriotic tissue into a male, it could not and would not survive. Based on all of these stated mechanisms, endometriosis affects enormous numbers of women. Yet confirmed 46 x y male cases are so rare that individual patients become medical publications. And when you examine many of those cases, you repeatedly find abnormal circumstances. Prostate cancer, estrogen therapy, androgen deprivation, cirrhosis, spironolactone finasteride, metabolic disease, previous surgery, Mullerian remnants, or some other abnormal endocrine, inflammatory, or developmental context.

And even the supposedly normal cases are usually not characterized deeply enough to prove normal molecular physiology. A 46 x y karyotype and normal external genitalia do not tell you DHT. Levels, S R, D 5 A activity, AR function, 3 beta dial metabolism, aromatase activity, oxidative stress, immune surveillance, or local inflammatory signaling. So those rare cases do not erase the male Protection model. They help us ask which barrier failed. And that is the part that should matter most for women. The goal is not to turn women into men.

So the Scientifically careful statement is not that an endometrial type lesion can never exist in a 46 X y person. Rare exceptions exist. The more useful statement is this endometriosis is not a normally occurring disease of the healthy eugenital male phenotype. Normal male development and endocrine biology create multiple sequential barriers that make spontaneous disease extraordinarily improbable. And the rare exceptions do not erase those barriers. They expose them. That is where the innovation is. Because if you allow yourselves to be swayed by agitators arguing endlessly over whether a handful of males have ever developed an endometriotic lesion, you fail to ask the better question.

Why do essentially all healthy males not develop one? Because, as most have come to realize, endometriosis is not the result of retrograde menstruation. Even the rare cases of endometriosis in males in which there was no malaria remnants have shown that it's best to look at the development, the steroid metabolism, DHT, androgen receptor signaling. Because the future of endometriosis should not just be finding better ways to suppress women. It should be finding better ways to make the disease biologically unable to sustain itself.

That's where we have focused our entire approach in the last seven years. So if you would like to get away from the hype and the agitators, check out our brand at ENDOLLS. Com.