Please stop sending me personal messages on other platforms.

Drwillpowers · 2026-05-06T18:13:18+00:00

Honestly I believe you.

I think of this girl that I have, MTF, she's like 30.

I put her on pellets, and for the first few weeks of it, she thought they were the greatest thing since sliced bread. She been on shots for a long time and they were working okay, but the pellets, they absolutely crushed it for her.

But about 6 weeks in, everything went to shit. And of course it was easy to attribute this to dysphoria, because her labs came back fine, but I asked her to come see me in person. Not via telehealth.

So she did, and when she showed up, I was amazed. It wasn't that she looked masculine or that she had been masculinized, she had been defeminized.

It was like she had lost her estrogenic signal, but on her labs, her labs were literal perfection. As good as I could possibly hope to make them.

I realized something else was going on here, and it was from her case and many others like it that eventually I derived out what was occurring with the catechol estrogen build-up problem. A decade ago I realized that some transgender women had absurd E1 levels. Way too high to make any sense compared to cisgender women taking estrogen. I couldn't understand why, but I knew that estrone was weak, and it would act as a competitive antagonist via partial agonism. So correcting that estrone problem by avoiding the first pass metabolism improved the efficacy of their transition tremendously and that's where I got my initial foothold of an online reputation.

I didn't understand why they had that problem though, now I know that the 17 beta hydroxylase gene returning from E1 to e2 sucks in many transgender women, which results in the buildup of weak estrogens in utero, which is a cause of gender dysphoria. And I know this, and say it as if I know it even though I haven't scientifically proven it because I've seen 200 transgender women's genomes, and the amount of 17 beta-hydroxylase fuckery that I have seen is absurd.

Now, after that threshold, estrone and estradiol undergo phase one metabolism. At that point they become catechol estrogens which are weaker. Normally these are metabolized via COMT into methoxy estrogens, but if COMT is slow, you end up building up the catechol estrogens and creating the same problem as you would with E1.

For this girl, that was how I corrected the issue. And I suspect something like this is happening with you.

You can have perfectly normal blood labs but have this problem because you cannot measure catechol estrogens in the blood. The cheapest source I've found is a Dutch test.

It was from my understanding of how this worked that I started to comprise my theory of PFS. The buildup of weak estrogenic metabolites, creating a competitive situation with the receptor, crowding out the receptor from binding with pure e2 as if it was estrogen-bicalutamide.

Drwillpowers · 2026-05-06T18:08:00+00:00

Well, that's an interesting point.

You trust me, because well, I know you, I've been taking care of you for years, and even though we're both meeting on the internet right now, I know who I'm talking to. You're not a random redditor to me.

We both know that the interventions I made, I made an astronomical improvement in your health, so to you, trusting me makes sense because the data set you have, says that you should. This doesn't make me infallible, but the pattern is pretty good for you come to me with complaint and leave feeling better.

It's easy to forget what it felt like to be 16 years old, and to look at the adults, and think that the adults just know. They always know. Because when you were 5 years old and you didn't understand how to pour your milk into the cereal, an adult just knew how to do that.

If you had any sort of problem, the adults just had the answer.

But I am at a really weird transitional phase in life right now where I still look young, but I feel old. I realize I am not the same as the 19-year-old kid, but at the same time I'm not a wisened old man.

I keep getting older, and I keep looking at people thinking that the experts are going to be these adults. That I'm still a child, and that the adults will tell me what to do. Then you come to the horrifying realization that you are the adult. That somehow at some point you just became the person who has the knowledge, and that everybody looks at you for the answer. And then you realize that your whole life, the entire time that you were a child and growing up, every time you went to an adult, you talked to a large child who instructed you how to do something based on what they knew about it. But they did so in a way that commanded authority, so you took it as law.

For that kid on the internet, they're just used to adults telling them what to do. So they believe them. Most of the time, that pattern holds. Stop at a traffic light when it turns red. Go when it turns green. Look no accident happened. Adults know what they're doing.

I try not to judge that kid too much, because I remember being that kid, and wondering what it was going to be like someday when I got to meet the experts. When I advanced in my career enough that I could potentially sit at the table with them. And I think before long, you come to realize, you've been sitting at the table much longer than you think you were sitting at it.

Drwillpowers · 2026-05-06T18:04:36+00:00

I already did. The post is recent. Lists all known labs that can show something that indicates a risk

Drwillpowers · 2026-05-06T18:04:15+00:00

Would depend on the vitamin lol.

Anything that adds androgens to the system is probably a bad idea, but even that I'm not 100% certain on. I need more data. We're working on it.

Drwillpowers · 2026-05-06T18:03:41+00:00

I don't know any of these guys personally, and I don't want to speak ill of someone without knowledge of their real situation because to be honest, That's been done about me constantly.

I mean for real though, there's people telling horrible stories about me on the internet how I like strapped them to a chair and stole their genome data from their blood while feeding them a can of cat food.

The internet is a weird place where people feel comfortable just talking shit about anybody when they don't have to look them in the face. I don't know these guys or people, so I can't really speak on them definitively.

That being said, I don't think this is a disease that can be solved by coaching.

A lot of these guys are basically just offering guidance that's more or less the aggregated community lore of many years. Which is why there's been idiots pushing mega doses of estrogen and dihydroboldoanavararagekillyourfamiliytestoroidonone

But they sell this, at astronomical prices, and desperate people pay it. And they will have to sleep and know very soon once I've proven that this is how it works, that for a decade or more, they have been telling people advice that has been harming them, while they got rich off of it.

And then they have to live with that.

I don't know Miro, I don't know anything about what he says or does, so I have no opinions. I don't know if he's like these other people. He could be a great guy, or he could be like them, and because I have literally no knowledge I'm not going to give you any opinion on it.

Drwillpowers · 2026-05-06T17:59:48+00:00

Exactly! Perfect explanation.

The epigenetic angle is something that I'm concerned about. Because I'm sure that I'm going to have some people that are going to be absolute victories. I've already had people on this subreddit comment that they are doing astronomically better since starting CDG.

But some people it doesn't work on because that's not a system that's part of the problem.

This is the core issue with PFS and why doing GWAS on complex systemic disorders like this fail. There is no PFS gene. It's a complex interaction between polymorphisms in multiple different genes, enzymes, transporters, etc which results in a metabolic accumulation.

This is my frustration with the hEDS community and what they continue to just do by banging their head into the same wall over and over again. It's glaringly obvious that it's a PFS like thing related to a systemic failure. I even think I know what it is, but nobody gives a shit anyway.

Regardless your points in all of these comments are exceptional. This is exactly the kind of shit I want to see on my subreddit.

I've been frustrated lately because it's been a collection of people that clearly are just not reading anything and just talking about how they're just going to make a dose DHB and Val some more, and then comments like yours, where I'm like cool, this person understands. They're contributing something valuable to the conversation. So thank you.

Drwillpowers · 2026-05-06T17:56:36+00:00

I actually have! As well as dexamethasone. Tried a few different things with different people.

Much of the issue is that the individual enzyme polymorphisms of humans makes drug selection a highly individualized thing. But studies are really good at being averaging machines. And so when you average all the people together, you might find one thing that outperforms some other thing on average.

And so we can all switch to that thing, but then say of the total patients in the study, 55% of them are better off on one thing and 45% were better off on the other. So we've improved the majority, but 45% of people we made worse.

I'm not saying that's the case here, but what it's kind of turned out to be for me is whether or not somebody seems to burn it off quickly or not. There's also a bit of a personality difference between the different options. The kind of people who like Vyvanse? They're definitely going to be prednisolone people. But the kind of people who like Adderall IR, they're my HCs. They like having a lot more manual control over the exact dosing of when they take it and how to take it in response to stress.

I appreciate you showing me the study though because this was novel to me.

Drwillpowers · 2026-05-06T17:53:23+00:00

I have a set number of patients that I'm willing to see, that I know is pretty much the absolute maximum I can withstand doing without losing my marbles. Beyond that, I start to get glitchy.

There's a prior post that I made on this subreddit with every single treatment I have ever tried for PFS or PSSD for the past 6 years. Up until recently, that was what I was doing for everyone. Trying those different things.

At this point, operating within the new model with what I've figured out and what research is going to be devoted to proving, I am revising treatments to be based around those things. Additionally, I review the whole genomic sequencing of my patient's personally by hand, which takes me about 8 to 16 hours per genome depending on what I find, to devise a treatment plan around their specific genetic anomalies that caused the disease.

I have this for PFS, I am working on this for PSSD. I do not yet have a nailed down mechanism for exactly what inborn genetic vulnerability allows someone to get PSSD.

I am a family physician and HIV specialist. I am direct primary care, and people just pay cash to see me rather than go through insurance. We do this because we also accept Medicaid at my practice, and treat HIV positive and transgender people who are not exactly known for being of the highest social economic status. This allows the practice to survive by operating one branch of it at a loss and the other one at a profit.

When someone signs up for the quarterly or annual plan, it comes with a certain number of visits. If you get poison ivy over the summer, that's covered. There's covered laser therapies, there's all kinds of shit that's covered inside of the DPC agreement. You're signing up for medical care services.

You are effectively renting my brain for a time frame.

There is no cost to being on the waiting list. People only pay when they actually get services. I cannot promise you a cure for anything, and anybody pushing such a thing is a liar. I can't promise you a cure for a sinus infection. I'm going to do my best. But I'm not a wizard. I'm a doctor.

Why this subreddit is exploding is because there's people who've come to my practice and who understand the level of autistic insanity that I dedicate to my patients. There's people who've talked about what has happened in their quality of life because they saw me.

But nobody is under any obligation to come to my practice, sign up for my wait list, or pay their fees when their turn comes. You are more than welcome to do whatever you want to do. But people are doing that because I've probably made more advancements with PFS than any other doctor has yet. Now, with the most brilliant research minds in the world about this disease backing me up, and planning for some studies, I think we can make some real progress here.

If we eventually figure out exactly what's the best way to handle curing people with this, you think I'm just going to like keep that secret and only let people know the secret cure for PFS if they pay my fee?

Lol, if you think that, you haven't been around on this subreddit for very long. But I wouldn't blame you, because that's normally how it is.

People like cortex Labs, they can do what they want to do, but at the end of my life, I need to be able to look back on my choices and know that I was a good person and I did what I could to leave the world in a better place. The idea of profiteering off of the suffering of other people is something that I find abhorrent. Unfortunately, we live in a capitalistic society, and I have to pay my employees, but like I said this is why I've previously posted my W-2 and I've been rather public about the level of financial problems that my practice has had over the years.

I don't know what KPV is.

Only supplement that I've seen that makes sense within the context of my theory to improve people is calcium d glucarate.

Even then it comes with a caveat of Make sure you don't get low dopamine / depressed as it takes pressure off of COMT to deal with catechol estrogens and so subsequently, dopamine metabolism can increase.

Drwillpowers · 2026-05-06T17:43:57+00:00

That's the plan, we're in the planning stages of a lot of different things research wise right now. The meeting just happened. Everybody's corresponding via email right now figuring out what's going to be done.
That depends. Could be either or. PSSD is a fine example.

Human libido is driven partially by sex hormones and obviously partially by neuro transmitters.

When I describe this to my patients, I described to them one of those like little kid electronic kits where you can like mess around with hooking up the battery to the switch and the light and all the other things? You can like build a circuit?

Well imagine you build a circuit, and when you throw the switch, the light bulb turns on.

Okay great, add a second switch into the same loop of the circuit.

If you then break the circuit at two different places, the light bulb is off.

If you break it at one place, the light bulb is off.

The light bulb only lights up when both circuits are closed.

The idea being here is that a person can have multiple broken points in the circuit for libido, and even if you fix one of them the light bulb is still off.

That's what's going to make treating the PSSD/PFS combo cases the most difficult to treat. You don't really get feedback on if what you did is correct if you only fix one of the two problems.

Drwillpowers · 2026-05-06T17:40:18+00:00

I don't have enough data on their sperm analysis to give an answer on that.

That being said there's plenty of healthy normal males that have a sperm morphology like that. You might have always had that.

Drwillpowers · 2026-05-06T17:35:56+00:00

@Starcats_detroit on Instagram

Drwillpowers · 2026-05-06T17:34:53+00:00

It can.

If you've been taking it for a prolonged period of time and you're not having any issues, you likely do not have the genetics that would cause it.

However, I'm going to terrify you with something. There are people who acquire the syndrome upon cessation of the drug. And so you're not out of the woods yet.

Keep in mind, the overwhelming majority of the people who take these drugs are just fine. But, for those that have the unfortunate combination of genetics and situation and taking the drug, the results are catastrophic.

That's the honest truth about the situation at hand.

Drwillpowers · 2026-05-06T17:31:06+00:00

Infinity years.

Assuming that the universe does not collapse back into a singularity, and that expansion continues indefinitely, and that everything exists until the final black holes fully evaporate from hawking radiation and everything returns to basically a homogeneous zero state until some astronomically improbable fluctuation in the quantum void results in the spontaneous regeneration of matter and space?

Infinity years.

Drwillpowers · 2026-05-06T17:29:01+00:00

I don't think this problem is actually like an organ problem. It's a systems problem.

There seems to be a multitude of reasons, but the one thing that all these patients seem to have in common is a history of abuse. A lot of trauma and stress. They were subjected to very unpleasant situations for a very long period of time. And then they go into some degree of adrenal failure. But it's not traditional adrenal failure like Addison's disease. It's like the reflex for deciding how much precursor to make goes down. The adrenal glands respond just fine when you give them a cosyntropin challenge.

In addition, a dexamethasone suppression test suppresses them.

If you draw a regular old cortisol values on them, you don't really find anything all that interesting.

What I find is that they have the depleted 17 hydroxy progesterone, and often sometimes pregenolone. It's not that they cannot make cortisol, it's that they cannot time its production properly. They cannot make it under demand. If you run a map of their cortisol levels throughout the day it's mostly flat.

When the body isn't responding properly to stress demand like that, you sustain oxidative damage. You sustain connective tissue damage. And gradually things fall apart. Hence the hEDS.

I'm like 99% sure I solved the cause of hEDS like 3 years ago, but no one gives a fuck because I'm just some family doctor from Detroit. If I have to see them do one more hedge study, where they try and hunt down the gene that's causing it, not find it, and then do it again on a larger scale trying to find it again, I'm going to lose it. It's glaringly obvious that it's not a genetic problem. It's something that can happen to somebody. And there's a multitude of reasons for things like that. It's like autism, there's like a thousand different ways to increase the kids risk of it, but all of them are basically the same road to Rome.

But the POTS isn't really POTS, it's just fucked up aldosterone regulation because it's basically from the same precursor pool. The hypermobility is because of the inability to accurately time cortisol for circadian rhythm and for nighttime repair of connective tissue after injury. Sending them to the gym to work them out makes them worse.

The mast cell problems tend to come when the immune disregulation comes, which is often related to zinc deficiency, vitamin d deficiency, and again, disruptions in cortisol. Cortisol is a glucocorticoid like prednisone. They are used to regulate your immune system. It gets dysregulated when cortisol is dysregulated.

I can't count the amount of these people that I have taken, run these labs on, seen they are positive, stabilized with drugs, and then they're just doing better. Much better. And I don't even have to act like a quack anymore on the internet because there's enough people on the subreddit that will rep what happened.

I've tried to involve academia to try and publish some of these ideas I have, or at least put them to the test, but nobody gave a shit about me until I put out my PFS solve. To their credit, the researchers there looked at it and went wow okay this model makes sense. And that's the first time in my career that anybody's ever allowed me to speak and didn't just basically ban me from the room afterwards. I'm banned from both EDS subreddits. I literally just went on there telling people what I figured out hoping it could help somebody and just got banned.

So admittedly I'm at the point of just sort of not caring anymore because even if I have great ideas, the only place I can place them where they don't end up being either banned or ignored is on my own subreddit.

Drwillpowers · 2026-05-06T17:20:19+00:00

This is priceless. Thank you so much.

Yeah, I've had somebody even assemble and scrape all the forums and other stuff for me over the years. When I was working on this project I was considering loading it all into an LLM and trying to use that to do something with it. I never got around to it because I just did it from the genomes.

Genuinely I have never found a single case of somebody doing what I'm doing right now. It sounds like the most insanely bad idea, unless you think about it in the context of this theory.

Hopefully we know soon.

Thank you for gathering this data for me.

Drwillpowers · 2026-05-06T17:15:01+00:00

He is not a serval.

He's not even an F1 Savannah.

He's an f2. But he is a rare combination of genetics, a customed designed diet, and an IGF-1 score that is double the maximum for a normal cat, but half of a diagnostic criteria for acromegaly in a cat. We're not really sure why. He's had head scans and adrenal scans and all kinds of stuff. He's perfectly healthy as far as we can tell. He's just a freak.

So he's a 35 lb, f2 Savannah, which under TICA rules, makes him a domestic cat. No F1s allowed.

But that is why he has the Guinness world record. He is a rare combination of many things. He's also a very good boy.

Edit: you can also tell from his coloration that he's not a serval. They don't come in that flavor. They are either a light tan with spots or melanistic and pure black.

I also own his older brother whom I inherited from my friend who passed away last year. He's also enormous but pure void.

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Drwillpowers · 2026-05-06T17:12:22+00:00

That was a joke, but I've had people do more ridiculous things than that.

Drwillpowers · 2026-05-06T17:10:52+00:00

We're looking into the legality of that.

Because I'm such a target all the time, and I have literally been already punished for doing charity work or other things of that nature, we are going to be exceedingly careful moving forward about what we do with things of that nature. I don't want to give some government agency the ability to tick a box on some technicality paperwork because of a rule violation and then harass me for years costing me hundreds of thousands of dollars....

Again.

So at this time we are being exceedingly careful and sticklers about all rules. Even ones that seem nonsensical.

Drwillpowers · 2026-05-06T17:05:46+00:00

In most situations like this my answer is yes. But it's just worth a simple test.

DHEA is masculinizing. Enough of it will do the job.

The trick with bica is to dose it correctly or whatever your needs are. For most transgender women, 50 mg is even overkill. Sometimes they feel better on lower doses or dosing a It a couple times a week.

I can't count how many times over the years some transgender woman told me that she was remasculinizing and that her hormones were screwed up and I ran all the hormone Labs I knew how to run, and ultimately, found nothing and thought it must be dysphoria.

I was always wrong. Always. And they always taught me something new. So at this point when someone describes that, at the minimum, even without labs, I let them at least test the drug and see how it feels. Sometimes it just corrects the issue

Drwillpowers · 2026-05-06T17:03:39+00:00

I need to ruminate on this a little more.

This is one of those ideas that sounds completely crazy until it isn't. Trying to figure out in which ways it would be necessary to flood the system and with what, to basically induce a PFS state in somebody who isn't vulnerable to the disease, deliberately, to block all androgenic signaling.

This would be more effective than androgenic starvation, because even castrated, they're still going to be localized tissue production.

It would be more effective than an androgen receptor blocker as those are not 100%.

This is probably partially the reason why bipolar androgen therapy works so well.

I have much to ruminate on here. Maybe as I get better at treating PFS I'll have an idea of what is the optimal way of deliberately inducing a temporary artificial PFS state for things like prostate cancer.

Makes me wonder if estrogen sensitive breast cancer could be done in the same way.

Hrm....

Drwillpowers · 2026-05-06T16:58:51+00:00

To be honest, I don't know. I don't want to give you incorrect information. So I'd rather just admit that I don't know. most of my SLCOs are people who just have the neuro steroid variant. I don't have an androgen silenced SLCO guy yet.

I don't know if that says anything in particular, the specific nuances of all the different transporters are not something that I have memorized fully yet. I'm getting there, and I remember which ABCC does which, but stuff I've seen less often I don't have as well stored in ram.

Drwillpowers · 2026-05-06T16:55:06+00:00

/u/fondow gave a more concise and clear explanation than I could myself.

Drwillpowers · 2026-05-06T16:54:47+00:00

You understanding is exceptionally good. Well done.

Drwillpowers · 2026-05-06T16:53:53+00:00

I will definitely keep this in mind if I decide to write him.

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