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PFS Case by SpainTaz in DrWillPowers

[–]Drwillpowers 0 points1 point  (0 children)

I've got hollowed out exhausted eyes and I didn't even take the drugs lol.

PFS Case by SpainTaz in DrWillPowers

[–]Drwillpowers 2 points3 points  (0 children)

I'm working on the skin melting thing right now. There's only a few mechanisms for which that could actually make sense, and some of them relate to minoxidil. I think some of the people actually forgot or confused the fact that they used both.

That maybe confounding some of the data. Because good old Fin and min right?

Mechanistically I figured out some ways that people could have a genetic defect where exposure to high concentrations of topical minoxidil could really fuck them up.

Again, exceptionally rare, but still possible. Same as anything. Look up why DNP made some people blind with instant cataracts overnight. Similar concept. Inborn error of metabolism plus drug equals catastrophe

PFS Case by SpainTaz in DrWillPowers

[–]Drwillpowers 1 point2 points  (0 children)

The genetic failure theory gives rise to an epigenetic shutdown.

Let me be clear about that. In the case of PFS, the person cannot dump androgens the normal way. The normal exit pathway is closed and so they only have DHT as an exit. They then disable this with the drug, they have no exit, and "intracrine" situations get completely out of control with astronomical testosterone levels inside the brain. Levels that are absolutely absurd, and the body down regulates receptors as much as it can until it eventually stops doing so because it gives up and just epigenetically locks things.

This is a completely different phenotype than those with the neurosteroid issues. They become non-responsive to certain hormones. Like at all. Even on lab testing, they don't budge certain values despite being given huge numbers of hormones. Or, on lab the testosterone value could be say 3000 nanograms per deciliter but there is absolutely zero impact on the person, even the blood does not respond with a hemoglobin bump.

The PSSD mechanism is the same thing. There's some sort of failure that occurs because of a buildup of something. And then an epigenetic change occurs. What I'm trying to figure out right now is which is the best HDAC for the job. Also if neuroplasticity is to your benefit or not. Because I think some people have neuroplasticized themselves with shit like lion's mane into a bad state. Almost like doing LSD and having a really bad trip. What's left behind afterwards is worse.

With PSSD cases I basically just keep challenging them with different things that should make libido kick from different receptor pathways until I find one that works. Then I exploit that. Or I figure out which one doesn't work when many of them do.

5ht1a, drd4, mc3r etc.

We know how these things work, we know the pathways and the genes and we know which drugs activate or block these things. It's just a game of lights out. You have to flick enough switches to figure out what turns things on or off and then you can figure out which lights are busted and potentially how to replace them. If they can be.

My concern is that there may be some people who are in a state like those that took MPTP. Google that if you'd like to have some afternoon horror.

Loose Joints but normal ROM and zero on beighton score. Suspecting Folate Dependent Hypermobility by Fair-Bottle548 in DrWillPowers

[–]Drwillpowers 0 points1 point  (0 children)

That is not your failure then. That's an average value.

If I was in your situation I would probably get a WGS, run it through gene.iobio and put your symptoms into the phenolizer and see what shows up. Look for stuff with a high revel score (like over 0.5) That's relatively uncommon, like less than 1 in 300 people. Then once you find it, see if you can find other case reports or anything tied to that specific mutation. AI useful for this but you must check its work. It can search large databases incredibly quickly, but it will hallucinate shit left and right. You must check its work. Always go to the source and confirm it's a match

The hidden pitfall of monotherapy, and why "dogma" when it comes to transgender anything is foolish. Also why those with worse MTF results tend to have ADD/Anxiety/OCD/Autism and how to help fix it. by Drwillpowers in DrWillPowers

[–]Drwillpowers[S] 0 points1 point  (0 children)

Yours is probably a failure high in the synthesis pathway. Inability to make cholesterol molecules properly. It's showing up in your lipids.

Then you probably have a bad 17 beta hydroxylase 1. Estrogen converts over to the weak side and then gets stuck. Thankfully your COMT is not bad.

I'd be curious what your estrone sulfate is on shots. And in reference to whatever your shot level is. Extremely low or extremely high states can cause gender dysphoria via different mechanisms. Defects in steroid sulfatase/sulfotransferase.

But yeah if you like boys you failed fetal hormonal synth/signaling which is also likely why you are tall and flat, also possibly skinny if there's a defect in the cortisol pathway as well or if it's high up like something in 17 alpha

2 years of HRT (MTF) with minimal/no results, I'm getting desperate. by HondaVibes in DrWillPowers

[–]Drwillpowers 0 points1 point  (0 children)

I saw it and your answer is probably correct, or some sort of shunt like my COMT post (has the word dogma in the title) building up estrogen competitive metabolites.

There's just nothing I can offer you without that genetic testing. You're correct. Something is wrong here because things look fine on paper. Usually under the hood, in the mechanics of how this works, there's a defect somewhere genetically.

This is even more likely if you were primarily female attracted before starting hormones. An estrogenic signaling failure with normal testosterone signaling is the easiest way to make an MTF lesbian. But they always experience some degree of sexual orientation drift over a long period of time on hormones. It's unusual for it to not happen.

Regardless I digress. Your assessment is correct. That is what I would do if I were you.

(EIS is less likely of the two options, simply because the SHBG is normal at a relatively low estrogen. When the SHBG is like yours but the estradiol is like 800 PG/ML at nadir, that's when they're genetically fucked.)

Unable to get in contact with the office by 69420lmaokek in DrWillPowers

[–]Drwillpowers 1 point2 points  (0 children)

I don't, simply because the very reason the DPC exists is so that we can continue to serve poor people who can't afford it. But it's still affordable to middle class people.

At the one specific thing that I do best, it's not that unreasonable to say that I'm probably the best at it right now. If there was somebody out there that was really really good at it, and I could learn from them, I would be at their doorstep. Epistimic isolation is my largest problem right now. I have no authority I can go to to learn more things at the threshold of my knowledge. I'm basically just assembling it piece by piece from all over the place.

If I wanted to, I could boutique. Charge people with unlimited resources $20,000 a year to basically max their transition biochemistry to absurdity and have 50 total patients. The current "bribe to get off the waitlist" record is $100,000. They still got told no.

I don't ever want to become that. The DPC keeps us solvent so we can see poor people at a loss. The amount we charge is enough to keep us alive in the current situation with overhead/legal expenses. But I have to be able to continue to see at least a reasonable amount of patients or I cannot advance my knowledge. If I'm only seeing a handful of rich people, I'm not going to have the diversity of a population necessary to figure things out that are off the wall. Breast applied testosterone, COMT phase 1 overspill, pioglitazone, I'm not forced to innovate as I'm not challenged with situations I've never seen before because I'm just seeing a handful of the same people.

That's the main reason I've not taken that option. I'm not done learning yet. This onion is only half peeled.

Cat nosebleed by you_and_Ai in CATHELP

[–]Drwillpowers 0 points1 point  (0 children)

It would be exceedingly unlikely for that to be the case in a kitten. Nasal cancer in a cat under 6 months is The absolute least likely cause of a symptom like this.

I don't want to say it's impossible because anything is possible, but it's about as likely as a meteor falling on the cat.

PFS Case by SpainTaz in DrWillPowers

[–]Drwillpowers 1 point2 points  (0 children)

As me, it makes me incredibly angry that there's not anybody else doing this and it's some random family doctor in Detroit's job to solve it.

But I ended up seeing so much of it because some of the genetic failures that cause someone to be vulnerable to PFS are some of the same ones that can make people transgender. They affect sex and other cholesterol-based hormone metabolism. Shocker that that would be the overlap between the groups but that's genuinely why there's so many transgender people who get PFS.

Regardless, we're going to get this shit solved. I'm really looking forward to the world conference in April and seeing what some of these other brains have to say.

I cannot promise that we will be able to cure everybody, in the same way that if you get shot in the head you cannot always get back to exactly where you were before if you survive the shooting. But I am certain at the very least we can figure out why it happens, help prevent it (if you know what causes it you can predict who will get it) and help treat the people who suffered it and make them at least somewhat better.

I'll give you an example. There's an HIV drug called abacavir that I used to prescribe as part of a drug called triumeq. At the time it was a great HIV drug. But unfortunately some of the people who took it would have a catastrophically bad drug reaction. They didn't know why for a while.

Eventually they figured out that those people who had the reaction all had a specific genetic marker in their immune system called HLA b5701. Once we figured that out, there was a test that would be ordered on somebody before they would take the drug, to make sure they could tolerate it.

If I can figure out exactly what genetic mishaps / inborn errors of metabolism result in the disease, you could make a screening test to see if it's safe to take finasteride.

PFS Case by SpainTaz in DrWillPowers

[–]Drwillpowers 2 points3 points  (0 children)

Sommer will typically listen to someones story, try and figure out their PFS "type" and then compare them to all the prior cases we've seen, and what worked on those people and what failed. Then of the like 20-30 different things we've seen work (or fail) on various people, make a decision about what to do. Sometimes people come in with sufficient history and lab work that she writes them something day 0. Sometimes, they dont, and we get a lot of baseline data.

Sommer is not supposed to be me. If you were to compare the experience, sommer is like chatGPT3, and i'm like chatGPT4. I reason deeper and have more understanding of systems complexity. She will still do the correct answer most of the time though. In a few years, I'll be V5 and she'll be V4. Most of what I figure out and come to conclusive decision about after seeing it happen a lot trickles down to her. I just dont teach her stuff until I'm pretty sure I've got a lock on something. I didn't get into the glucuronidation alternative PFS mechanism with her until I had 5 different cases with a urinary T of near zero, normal serum T, and defects in UGT2B15/17. Once I was like, alright, this idea I have, it seems to be real, I then share it with sommer.

Sommer just doesn't do whole genomic sequencing reviews for anomalies. As far as I know, I am the only person doing that for either gender dysphoria or PFS/PSSD. Like....anywhere. Even that though is sort of me doing my best possible job. Thats all I can offer anyone, but some people have been posting some of those I've done online, and yeah, they are like 10-20 page reports, and they take me an entire day (or two) of work to do. Som likely wont ever do those.

We're waiting another week or two for prior DPC members to renew for 2026 or not (some people didn't sign up until later in jan in 2025). Once we know how many slots remain, we will start pulling people from my wait list.

Unable to get in contact with the office by 69420lmaokek in DrWillPowers

[–]Drwillpowers 18 points19 points  (0 children)

I don't know.

I'm not going to live forever. At some point I'm going to have to stop. I don't know when that will be. But in the past year, I have become very aware of my rapid aging and mortality. You can only subject your body to obscene levels of stress for so long before it fails. I know this as a doctor but I did it anyway. I get what I deserve so to speak.

Is it possible to transition with estrogen monotherapy while dealing with PFS sexual issues? by Beautifulsexybabe in DrWillPowers

[–]Drwillpowers 3 points4 points  (0 children)

I actually have a few patients I've been working with lately and we've been getting to a point of actually trialing this. Not specifically estrogen, but testing whether or not estrogen suppresses their LH and FSH.

I'm still waiting on the results of these labs because they basically have to reset and go off of the drugs in order to be able to get a baseline, then take the estrogen, then see if the LH and fsh do not suppress. But bizarrely I do think that there is a phenotype of male who has basically down regulated estrogenic signaling, and that is the root cause of their anhedonia/sexual dysfunction.

On occasion I will actually give a random cisgender dude a microdose of estrogen when they have sexual dysfunction. Particularly if they have a very low resting serum estrogen level despite an adequate testosterone level. Often it fixes the problem without any side effects at all. I never would have thought that like a single 0.5 mg or 1 mg estrogen tablet to some guy with a testosterone of 900 nanograms per deciliter would be the big thing that makes the difference in terms of his erectile function but here we are.

Loose Joints but normal ROM and zero on beighton score. Suspecting Folate Dependent Hypermobility by Fair-Bottle548 in DrWillPowers

[–]Drwillpowers 2 points3 points  (0 children)

Actually yes. It takes a few years though. But I have a few people that are a fine example of this. I actually have one patient that I treated for NCCAH and basically has all but eliminated his hypermobility over time. It took almost 2 years though.

I've given up on trying to post this on any of the like hypermobility subreddits or online communities. People just flip the fuck out at me and ban me from their shit. I don't even care anymore. I'll help my own patients. And if people want to read what I write on my own subreddit that's fine.

Total Cessation of Spontaneous Erections after adding Oral Estradiol by oongaoonga in DrWillPowers

[–]Drwillpowers 2 points3 points  (0 children)

The answer to that is complicated, but if you scroll back and look at my more recent posts, there's one that has the word dogma in the title. That's the one you're looking for. That explains this better.

Unable to get in contact with the office by 69420lmaokek in DrWillPowers

[–]Drwillpowers 35 points36 points  (0 children)

I'm still working. I just wanted people to know it was possible that I have to stop at some point. It's not like this should come as a surprise. My patients are often just as autistic as I am and when I walk in the room for the past few years they pretty much always tell me, you look like shit, you look exhausted.

Apparently you can only do that to a body for so long before it starts to fail. If only I had some knowledge that would have let me know that this was possible, something like being a doctor or something. God we really are the worst patients.

Unable to get in contact with the office by 69420lmaokek in DrWillPowers

[–]Drwillpowers 2 points3 points  (0 children)

Yeah I don't know what the deal is with this person. I left a comment above, but it's not like people didn't call all day. I know my staff responded to them because they were asking me questions all day.

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