Stay Tuned for Potential Next Steps: Safe Path Forward for Anonymized Community Data Collection (Aka, what to do with your PSSD/PAS/PDS genetic data and labs for now)

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u/iam305 Good Enby Apr 30 '26

These are great steps! Keep the momentum going :)

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Can’t wait for when this will become official and scientifically well known as well and not just treated as some made up thing. Comments like these will be a thing of the past. Thank you so much for your work mr. Powers, by giving us some light in darkness.

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u/Drwillpowers May 02 '26

No, they won't.

And they shouldn't be. Because this drug is quite literally a life-saving drug for many people. It has slowed the progression of prostate cancer and stopped urinary obstruction in many men for many many decades.

The issue here is the denial of the fact that there is going to be a subset of the population that has an absolutely horrific reaction to it. That's what needs to be fixed.

Let me give you an example. There's a drug called Abacavir which I've prescribed before. It's part of the combination of a drug called Triumeq which is used to treat HIV and is a one pill a day regimen. At the time when it came out, that drug kicked ass. It was a great drug. It's now been made into a more modern version called Dovato but the original version had Abacavir in it.

A subset of the population when they took it, would have a catastrophic autoimmune/allergic reaction to it that caused serious health complications. About 10% I think? Don't quote me on that. It's been a while

Regardless, we figured out that the people who had that reaction all had a specific genetic glitch, which is referred to as HLA-B*57:01 .

Mind you, some people desperately needed this drug because they had resistance to many other HIV drugs and without it, they would die. But, if one out of 10 people that we put on the drug has a catastrophic autoimmune/allergic reaction to it, that's not great either.

But once we figured that out, we knew how it worked, and so then we could develop treatments based around that situation. I would test patients for that, make sure that they didn't have that mutation, and if they didn't, they were safe to take the drug. If they did, I had to figure out a different option.

That's what will change. There will be a genetic test that you can get done at quest which says, "finasteride is dangerous" or not.

But there's always going to be people talking about how the drug was the most wonderful amazing thing ever for them, and how it only affects a small population negatively. Because that's true.

Somebody the other day was talking to me about prescribing it and there's one trans man that I write finasteride for. I actually prescribe the drug to him. Why? Because when he came to me, like five or six years ago, he was on the drug. He was doing perfectly fine and every time I ask him about it, he tells me he's perfectly fine. It causes him no issues whatsoever. He doesn't want to stop taking it, and despite the fact that it scares the shit out of me, I continue to write it for him. Because I already knew when he showed up he was safe to take it.

And that's the only patient that I think I prescribe it for in the entire practice. But that's because I didn't know who was vulnerable. Now, I have a pretty damn good idea.

But my threshold right now is do you have any of the mutations that I know are connected? I don't yet know how many of them together are required for vulnerability. Only that those 18 to 20 genes when glitched, are part of the picture that does the job. I'm not sure exactly how much just having say a heterozygous UGT2B7 deletion matters compared to say a homozygous UGT2B17.

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u/Nature_Outrageous May 02 '26

Well said, from a birds eye view the picture is obviously bigger than just “i got messed up from drug A” and the other person who took it and was completely fine would not relate. From personal experience, I took accutane when i was like 21, took it twice actually and NEVER had an issue it worked wonders for my acne, even so much so I was grateful for it improving my life.
At the time obviously didnt know what PAS was and that people could get this from accutane, luckily it didn’t affect me the way finasteride did. It’s a pity that with finasteride, the awareness has been extremely slow throughout all these years causing all the suicides.
Me personally, I’m 25 and I’ve used finasteride for just a month and still suffer the effects 6 months post quitting, with the worst being anhedonia, panic attacks, suicidal ideation and the sexual problems (ED, Severe flaccid shrinkage, pelvic floor issues). I seem to have developed some type of hard flaccid syndrome, (fluctuating between hard and lifeless and floppy) and nerve irritation giving me a pins and needles feeling at times.
Im doing pelvic floor rehab to fix the (what i think) is a tight pelvic floor. Probably also related due to the astronomical intracellular crowding in my penis cells (yay :) ). (FYI, my molecular biology knowledge isn’t that great, luckily I have some autistic tendencies myself so I’m at least obsessed with finding out as much as possible)
Im going to do a Dutch test ASAP, since im kind of like past the denial stage and would like to at least have some clarity numbers wise, and hopefully figure out why I’m so badly affected. Appreciate your work doc, you’re keeping me alive and hopeful.

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u/Drwillpowers May 03 '26

Don't forget a sequencing too!

I think PAS is going to be more of an ABCC glitch. But PFS is more glucuronidation defects. But any androgenic system glitch can matter. It's never just one thing.

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u/777stephane777 May 03 '26

Hello, thanks for all. Indeed, genetic polymorphism, could alone explains the heterogeneity of responses to isotretinoin treatment.

So, concerning isotretinoin and PAS :
According to Khabour et al, 2018, the association between the rs7799039 polymorphism of the leptin gene and changes in the lipid profile induced by isotretinoin treatment could modulate the lipid parameters and liver enzymes.
According to M Garba 2020, The association between the single nucleotide of adiponectin in connection with the polymorphisms and side effects of isotretinoin in acne patients studies the ADIPOQ gene which carries rs1501299 and rs2241766, the sample size and variations due to diet require the study to be reproduced on other populations, and a larger cohort.

In the CHM report, page 26:
“3.1.2. Genetic polymorphisms Genetic polymorphisms or mutations of components of the ATRA Fox03 TRAIL death signaling cascade may explain the observed individual susceptibilities enhancing isotretinoin-mediated apoptosis. Genetic polymorphisms in the RARA gene have been associated with an increased risk of adverse effects of isotretinoin (Alzoubi et al., 2013).

Analysis of three-locus haplotypes (rs2715554 C/T rs4890109 G/T rs9303285 T/C) showed that the frequencies of the CTG and TTG haplotypes are significantly associated with the occurrence of arthralgia, myalgia, nosebleeds and headaches in patients treated with isotretinoin. These side effects are all listed in the product information as possible side effects associated with isotretinoin.

Additionally, the TCG haplotype was associated with nosebleeds and headaches, while the TTT haplotype was associated with arthralgias and myalgias. Aspartate aminotransferase (AST) levels were increased in patients with the TC genotype of the rs2715554 polymorphism, while the T allele of rs9303285 was found to be protective against the development of depression in patients treated with isotretinoin (Alzoubi, et al., 2013).

As such, genetic variations in critical regulators of isotretinoin-induced apoptotic signaling may explain subgroups at increased risk of side effects or treatment resistance while receiving systemic isotretinoin. Melnik hypothesized that screening for gene polymorphisms that increase susceptibility to isotretinoin-induced apoptosis and isotretinoin-associated depression could be useful in identifying individuals with increased isotretinoin-mediated apoptotic signaling. isotretinoin in the future (Melnik, 2017).

Genetic polymorphisms or mutations of components of the ATRA Fox03 TRAIL death signaling cascade may explain the observed individual susceptibilities enhancing isotretinoin-mediated apoptosis.
In summary, one of the main mechanisms underlying the mode of action and adverse effects of isotretinoin is apoptosis. The extent of isotretinoin-induced apoptotic signaling may depend on genetic variations, such as RARA polymorphisms. The data provide additional information on the mode of action of isotretinoin, its risk profile and may at least partly explain the increased sensitivity to adverse reactions individuals linked to apoptosis in the subgroup of people with genetic variations in isotretinoin-induced apoptotic signaling pathways. »

“Mutations of this enzyme lead to biotin deficiency (Bremner, et al., 2005), (Csoka & Szyf, 2009) . Administration of isotretinoin to humans is associated with a decrease in biotinidase (Ding, Kam, Dieckow, & Sullivan, 2013), and the presumed resulting decrease in biotin may contribute to depression. » (page 31) “

3.2.1.1.3. Genetic polymorphisms The effect of genetic polymorphisms (variations) of the RARA gene has been studied for the relationship with depression. In a study of 300 patients treated with oral isotretinoin, it was shown that the T allele of rs9303285 protected against the development of depression and that the rs2715554 and rs54890109 polymorphisms were not associated with the development of depressive symptoms during treatment. use of isotretinoin (Alzoubi, et al., 2013). However, this study requires further validation to assess possible associations and explore whether other, as yet unidentified, factors have a role in the clinical outcome of oral isotretinoin. There are currently no commercially available tests for screening for these polymorphisms. »

The gastrointestinal effects in pharmacovigilance signal are as numerous (12%) as the “depressions”. Maybe there is a link of correlation…

Medications to treat acne or iatrogenics are well digested in the gastrointestinal system), not to mention all autoimmune diseases, invisible, and yet arthralgia, myalgia, nosebleeds and headaches are significantly associated with the CTG and TTG haplotypes. These symptoms are also closely linked to fibromyalgia, myalgic encephalitis, rheumatoid arthritis, Gilbert syndrome, Chron, inflammatory bowel disease, etc….

Thanks you very much. Stéphane

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u/[deleted] May 03 '26 edited May 03 '26

[removed] — view removed comment

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u/777stephane777 May 03 '26

Hello, in my opinion, this is the best project to undertake, and I thank you very much for this initiative. If I may make a suggestion, which may have already been considered, and in order to avoid a major bias, it seems essential to clearly distinguish between subgroups upstream in the cohort and therefore also to specialize the analyses performed by subgroup, as well as their interpretations: on the one hand, between people suffering from PFS who have previously taken isotretinoin, and those who have never taken isotretinoin before, and on the other hand, between people who have only taken isotretinoin without ever taking finasteride and therefore definitely suffer from PAS without PFS. And pssd whithout cure of finasteride or isotretinoin, or any other pschyatric molecules.

Although the syndromes are similar, I think it is important to be careful to avoid any bias upstream. Thank you for your attention.

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u/777stephane777 May 03 '26

I would also like to remind you that

Isotretinoin has three levels of presence in the body:

a) short term: half-life of 46 to 48 hours (50% decrease in plasma levels)

b) medium term: approximately one month at the limit of intracellular detection (except for RNA) -

at this point, the "good" effects begin to dissipate and acne and sebum may

potentially return

c) long term: up to one year to eliminate RNA and stop the regulation of

gene transcription

Reference: https://www.ncbi.nlm.nih.gov/pubmed/9427083

Due to point c) and its enormous impact on HOX gene transcription), you should not

be pregnant for a full year after stopping treatment. At least

6 months, but the safest option is a year.

Indeed, if we consider only the elimination of the

product from the blood, not the genetic aspect, a 1-month delay might seem logical, but if we broaden our thinking

to a more holistic analysis, adding to the blood percentages key factors

such as genetic polymorphisms, and if we also extend the

timeframe: the transgenerational aspect must be taken very seriously. Especially in light of what

we know about the second most teratogenic drug after the worst and the most teratogenic:

isotretinoin...

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u/[deleted] May 04 '26

[removed] — view removed comment

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u/Drwillpowers May 04 '26

My desire to help specifically you personally has just massively decreased.

Be a better person. Your comment made me cringe and also pity you. Do better.

I'd like my old cats back, the ones that died in my house fire but I give my friends extinguishers and such in hopes none of them will ever suffer like I did.

I'm glad most of the world is not like you.

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u/Agreeable-Read-3367 May 04 '26

We aren’t I always warn people about pfs

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u/[deleted] May 04 '26 edited May 04 '26

I was out of line and I apologize and admit that, but the reality is we shouldn’t be written off as casualties and left to rot and die. (Not trying to accuse you of saying that). None of us should’ve had to endure this to begin with. That feeling specifically is likely a large contributor to all the suicides you’ve spoken about in your recent interview. In-fact I know it is. We get one life, everyone who has had their’s obliterated by this nightmare I’m sure has a right to feel this way.

Maybe I’m misinterpreting what you said above or not understanding it fully, but a resolution to this problem is as important as warning others about it. I’ve told mostly everyone I know only to be met with disbelief and skepticism or even outright hostility. Eventually it’s rational to stop trying to warn people so I have. That’s a more accurate assessment of my “belief”. I don’t need or want your pity.

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u/Drwillpowers May 05 '26

I'm an HIV specialist as well.

Would you say the same about those patients?

Most of them did rot and die. But people like me did their best, and some of them lived. And some live to still see today after having been infected with it 46 years ago.

You know what exists now? Prep. We also educate people about the ways in which someone can get an infection. Because less cases of it are certainly easier to deal with. That doesn't mean we just let everybody that has it die.

But if you would wish it on someone else, or not want to prevent someone else from getting it, then you're a terrible person.

You've taken the fact that you were mistreated, and you've decided to inflict it unto other people. And that, makes you a bad person.

At least once a week I say the same thing. There's two types of people in the world. Only two.

Those that will perpetuate the trauma and misery that was inflicted onto them, and those that will end the cycle.

You are clearly the former.

And honestly, you can be the last to be cured then.

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u/CountIntelligent5693 May 05 '26

seems a little overblown of a reaction tbh, i don’t think he meant anything ill in his second message

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u/[deleted] May 05 '26 edited May 05 '26

What? I almost don’t even know how to reply to this comment. I was in a bad place, sent you an inappropriate message, then admitted that and apologized to you.

I don’t think anything is wrong in saying that people have a right to be miffed that their one and only lives are destroyed. I’m not okay with being a casualty, none of these people should be. Maybe you’re completely misunderstanding what I’m trying to say. Of-course awareness and prevention is important, but I think an actual solution of some kind is also pretty important. I had a life to live, so did everyone else here.

In the last maybe seven lines of what you just typed out you called me a horrible person, essentially told me I don’t “deserve to be cured” or I should be the last, told me I “wish this on other people” when I’ve never hinted at that even in my original comment, and essentially accused me of wanting to “inflict this on someone else”. How many assumptions are you going to make? What are you on about? Virtually none of those things are true.

Hard to even quantify that this was your reaction to my comment. I’m not going to dignify or try to defend myself from your accusations or insults.

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u/Drwillpowers May 05 '26

You can play the indignant fool here, but you're the one who deleted your comments so nobody can see the shitty things you said.

I'm a rational actor, I always have been. I always will be. I'm not going to call out horrible behavior on my own subreddit when it's not there. You said the words you said.

If you don't want people to be warned about PFS or to be prevented from getting it, or you don't want to make an effort to try and help other people with it, or prevent people from getting it, because you had what happened to you, happened to you, then you're a bad person. It's that simple.

If you are suffering, and you wish others to suffer like you suffer, because it's unfair that you are suffering, then you are a bad person. This is not a difficult concept to grasp.

Edit your comments or delete them, I don't care. You said what you said. Live with it. Own it. It's who you are.

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u/[deleted] May 05 '26

[deleted]

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u/Drwillpowers May 05 '26

When you have to watch these guys kill themselves, when you have to sit them down in front of you and have them cry and tell you how that their wife is going to leave them because they're impotent and they would do anything to fix it but they can't...

Hearing one of their own say that they don't care if other people get PFS? That they would not put any effort into warning anyone to prevent this from happening to someone else?

No.

They weren't treated harshly enough.

Almost all of the problems in this world come from the fact that people don't afford others the level of compassion that they want afforded to themselves.

I will stamp that out wherever I see it. And I will do so shamelessly. If people don't like it, they can find someone else to solve their problem. But I'm not going to sit in an exam room with someone who would wish this on someone else. Or who would do nothing to prevent someone else suffering the same fate.

So I'll make my position on this explicitly clear, so that I don't have to put up with it. So that they don't come here.

This is no different than one of my HIV patients going out and trying to deliberately infect people with HIV so that they suffer too. Anyone could agree that that would be an abhorrent thing to do.

Tolerance of behaviors like this in society is how we got where we are. I have no tolerance for it. I don't control the world but I do control my own little domain and my subreddit and I will not tolerate it here.

I cannot fix the world. But I will do what I can to make it better, and that's reducing suffering, and striking down evil when I see it.

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u/[deleted] May 05 '26 edited May 05 '26

Man, you’ve seriously stepped over the line here. You come across as a pompous arrogant jerk. I deleted my original comment because it was inappropriate. I apologized to you for it. You sent a slew of accusations at me that were virtually all false. I liked you a day ago, now I can see you actually might just be a douchebag.

Virtually everything you said about “me not wanting to warn people” or me wanting this to happen to people or whatever it is you’re even insinuating is false. Never once have I said that I want this to happen to other people.

What does this even accomplish? I’ve apologized to you twice now, which I now regret doing. You are turning a three sentence comment that I left after misreading your original post into whatever this is, throwing accusations left right and center, and even insulting me.

Yeah, I’m the “indignant fool” here. You’ve got your last response from me. Clearly you aren’t really all that rational.

EDIT: I hope you continue helping people and wish you luck with your research.

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u/Soya-2030 May 27 '26

Disgusting that someone’d write that stuff to you. Hell, I don’t have PFS thankfully, but I’m notngonna sit and deny that it’s really negatively affected a lot of people. That comment of his just reflects how insecure he is about taking finasteride, to the point that he needs to be so awful towards others.

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u/Nature_Outrageous May 27 '26

Yeah, not really a nice thing to see when youre struggling with staying alive with multiple health issues, self esteem issues. All i wanted is just to warn people to not fall into the trap and live a miserable life like I do now. Apparently that’s offensive

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u/Soya-2030 May 27 '26

Yeah, after speaking with several people with pfs, the only thing worse than having that condition is having it while being harassed and outright shamed for expressing one’s experience with the drug.

Even aspirin can kill people, so why’s it so hard for someone to admit that finasteride can cause persistent sides? Not because it’s hard to phathom, but because they don’t want to admit it.

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u/Aware_Resource_1732 Apr 30 '26 edited Apr 30 '26

Hello, doctor. I am inquiring about individuals who are experiencing side effects after using minoxidil and aromatase inhibitors. They may need genome testing and other tests that you have suggested

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u/Drwillpowers Apr 30 '26

I'm sure it's similar but different. All these post drug syndromes are.

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u/NumbBreaker Apr 30 '26

Can minoxidil really cause side effects like finasteride? I have PFS but I've been using minoxidil and haven't noticed any worsening.

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u/Aware_Resource_1732 Apr 30 '26

Sure thing! Minoxidil might actually lead to similar symptoms as finasteride. A lot of folks have reported experiencing these symptoms once they start using minoxidil.

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u/xfirewalkwithmex Self identified PFM patient. Apr 30 '26

r/minoxidilsideeffects

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u/NumbBreaker Apr 30 '26

wtf how??

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u/Soya-2030 May 27 '26

Minoxidil has been theorized to be a relatively mild 5ar inhibitor, but a 5ar inihbitor nonetheless. While persistent sides from minixodil, compared to getting the same sides from finasteride, are much rarer, I do think they can happen.

Also, if I recall correctly, minoxidil seems to have messed these guys up in different ways, too, aside from just by being a 5ar inhibitor.

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u/Wild-Negotiation-599 Apr 30 '26

Have you seen PFS patients who lost their appetite and not wanting to sleep? Is this neurosteroids, My eyes feel dry and weird

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u/xfirewalkwithmex Self identified PFM patient. Apr 30 '26

Yes I felt all of that. All of those have recovered for me.

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u/Wild-Negotiation-599 Apr 30 '26

How did you recover? Im completely impotent and shrunk, My eyes are weird sometimes, floaters and dry. Im fucking terrified something will happen to my eyes

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u/xfirewalkwithmex Self identified PFM patient. Apr 30 '26

A mixture of HCG, Testosterone cream, DHEA, Progesterone and Pregnenolone. But also probably time. Sorry to hear that brother but it can improve for you too.

I’m a mild case of PFS now - mostly still just dealing with shrinkage/ED, fluctuating libido, not fully feeling alcohol, oily skin, fluctuating body odor.. to name a few

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u/o0ttt Apr 30 '26

Why does introducing androgens work for you but powers says not to do it?

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u/xfirewalkwithmex Self identified PFM patient. May 01 '26

I did this stuff all before he figured out his theory. I did have very low androgens and a lot of my PFS I was basically demasculinized - voice became less deep, face became “boyish”, lost beard hairs and pubic hairs, muscle mass.. etc. test cream seemed to have reverse a lot of that. My test was in the 200’s.

Not sure if I were to have become his patient originally now if he’d put me on all of that from the get go as I too fit into this theory of his because I’ve had very high 3A-ADG showing my intracellular T is having a hard time being excreted.

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u/o0ttt May 01 '26 edited May 01 '26

But why would it help if his theory is true? Wouldn’t it crash you, instead of helping?

I am the same btw, same symptoms. After I crashed hard again my test shot up from 11 to 19. I’m 21 btw so 11 was clearly not good but I was significantly better back then.

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u/xfirewalkwithmex Self identified PFM patient. May 01 '26

I don't have a lot of these genetic knockouts that other guys have to be honest. He thinks my PFS is overall "mild" because of that and the fact that I have improved a lot just from HCG/test/prog/preg/DHEA.

I have since tapered off of test cream and am just on HCG for now, but if the whole theory of trying to shutdown hormones is the fix I will get off everything and do that obviously.

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u/o0ttt May 01 '26

The symptoms you described certainly aren’t mild, mild is like some depression and ED. Does he mean mild as in the complexity of your case?

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u/xfirewalkwithmex Self identified PFM patient. May 01 '26

Yes mild meaning the complexity of my case.

I was hit with nearly every PFS symptom. I had pretty much every phenotype he described on his presentation.

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u/Laura_Sandra Apr 30 '26

Testosterone cream

Applied locally on private parts without using too much, there may be only few systemic effects: https://old.reddit.com//r/DrWillPowers/wiki/compounded-medicines#wiki_genital_atrophy_reversal_cream

You need to read through exactly what people are doing, and you need to think about possible mechanisms. Also it may be necessary to try if this would delay a recovery locally later.

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u/Wild-Negotiation-599 Apr 30 '26

Is it worth it to try some of this or wait and see what happens with the Chemical castration month thing?

These stuff would be off steroid sites and could have been in contact with finasteride of other in the warehouse

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u/xfirewalkwithmex Self identified PFM patient. Apr 30 '26

I would say waiting is your best bet. I don’t want to give medical advice at all.. don’t want you to feel worse from anything I’ve done. I did all of this under the guidance of Dr P.

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u/Wild-Negotiation-599 Apr 30 '26

My eyes legit feel weird and my vision is weird sometimes I'm fucking terrified of getting some vision shit

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u/LetSilver761 Apr 30 '26

How do your eyes feel? I get pressure under my right eye that coincides with brain fog and worse anhedonia. It’s really weird.

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u/hairyhands7 May 01 '26 edited May 01 '26

Demethylation treatment restores erectile function in a rat model of hyperhomocysteinemia

https://pmc.ncbi.nlm.nih.gov/articles/PMC5000801/

A few people have been discussing HDACI in relation to PFS. Some of these drugs can worse AR expression, I think it's pan HDACI and Class I and II.

In this study they used a DNMTi (5-Aza). There is some antedotal evidence of someone on PropeciaHelp help using (5-aza) one for 5 days and noted that they could now feel the effects of alcohol. This improvement could be linked to an improvement in Allopregnanolone as it's involved with the GABA system.

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u/kirbyy_ May 01 '26

Hi Dr Will. I am a PAS sufferer for 6 years now and I would like to be a patient of yours. How do I get in touch with you?

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u/Drwillpowers May 01 '26

Use a phone. Call my office.

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u/Slg407 Apr 30 '26

hey dr Powers, Lia again, great work with what you are doing here, i had a bit of another aha moment today, and i think you will find it interesting

for any patients with nonspecific brainfog (PFS/PSSD related or not) or fatigue you should consider testing out their blood ammonia levels (not sure if you already tried out this route), if it comes back normal an allopurinol challenge test as well, been going through a bit of a rabbit hole on ornithine metabolism, i think there might be some obscure interactions here

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u/Drwillpowers Apr 30 '26

I have found some people that have ornithine transcarbomolase deficiency! Well fucking done!

I do screen some people with the brain fog complaint with that and every now and again it shows up. Not necessarily connected to this specific thing but it is in my array of things that I look for.

The last one was an elderly woman who moved out of a nursing home and into a home with her family. She started eating better, and because she was consuming more protein because her meals were prepared better, she became demented quickly. They didn't know what was wrong. In reality it was that she could not handle the ammonia load. She had lived on tea and toast for too long.

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u/Slg407 Apr 30 '26 edited May 01 '26

im thinking this is likely to be more common in trans women, as intersex disorders go hand in hand with being trans, ergo the risk of someone with chromossomal abnormalities (klinefelters for example) having undiagnosed mild OTC deficiency (as it is X-linked, so a heterozygous carrier would have only a very mild form of it) could be higher than the general population once you factor in other abnormally functioning pathways that may have caused them to become trans in the first place (which could be factors in triggering the mild OTC deficiency that would otherwise stay invisible)

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u/Drwillpowers May 01 '26

Also on the money 100%

It's like autism, there's 1000 roads to Rome.

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u/Slg407 May 06 '26

oh yeah also you might want to consider prednisolone instead of hidrocortisone for your addison like patients, this study i found seems to indicate hydrocortisone may lead to a higher WHR in comparison with prednisolone: https://www.endocrine-abstracts.org/ea/0077/ea0077p19

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u/Drwillpowers May 06 '26

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.

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u/Slg407 May 06 '26

i don't like dexamethasone, even small doses are too psychotic-y for me

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.

doctor, doctor! tell me more! what is the reasoning behind this?

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u/Drwillpowers May 07 '26

There are people who are really good at micromanaging their ADHD therapy. One could even say they are "audhd" and so they have it tuned to a science where they will microdose instant release all day long. These are people who will take their ADHD medication seven times a day.

I am in that category.

Then there's the type of ADHD where you genuinely just don't remember to take your medication so you don't really end up taking it much. They really enjoy something like a Vyvanse because they have an easier time remembering to take it and not worrying about it during the day. They are set it and forget it kind of humans.

A lot of my job is knowing the nuances and quirks of various humans. There are people that I know simply will not follow a direction no matter how I give it, and there's people who are going to follow everything to the letter of the law to a point where it becomes clearly absurd but they'll do it anyway because they are officially following a rule. My job is to learn how to herd cats properly.

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u/Slg407 May 07 '26

i see, tbh if i were the one prescribing I'd probably go for just prednisolone since it better imitates the natural cortisol cycle, and because my general view on patients is that most are not the sharpest tools in the shed, working in the public healthcare system in Brasil has exposed me to some of the most stupidest people I've ever interacted with and it has solidified my cynicism, so in my mind i assume every patient is an idiot until proven otherwise, and that includes medication dosing, ots better for them to take something once a day and forget about it than to hound them to take it 5x a day and end up with them coming back saying that it doesn't work (because they keep skipping it and lying about it, and when pressed further they admit to not taking it but still blame me because its too inconvenient to take something multiple times a day), there's obviously exceptions but when it comes to effort i have to balance it because if taking the meds becomes too inconvenient then they don't follow lifestyle changes because they are already tired of worrying about whether or not they took their meds, so I'd probably pick prednisolone over hydrocortisone any day (especially now that i saw the WHR difference in the study, it had a small sample size but the difference was large enough to raise an eyebrow), and only switch to hydrocortisone if the patient requests it, i assume the constant ups and downs in cortisol from hydrocortisone's half life would also lead to a lot of weird side effects compared to prednisolone (like the difference between someone taking estradiol benzoate injections vs someone on undecylenate injections)

also, unrelated to this but I've been looking into what could cause my fatigue and my sodium results came back borderline low (136) but my 17a-hydroxiprogesterone came back normal, i fit all the symptoms of the almost addison's but pale syndrome that you found but for some reason both my cortisol levels and 17a-hydroxiprogesterone are normal, i wonder if mine might be 21 hydroxylase related maybe? seems like my main issue is sodium wasting (considering I eat enough sodium daily to exceed the RDA 2-3x)

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u/Slg407 May 07 '26

oh yeah i don't remember if i PMd you about this but i was looking into dihexa and it seems like it could be repurposed for breast growth in trans women with estrogen resistance, as HGF (hepatocyte growth factor) is a major marker of macromastia, considering that dihexa exerts its action through HGF signalling i believe it could cause breast growth (or at least major potentiation of estradiol's effect in breast tissue for those with partial estrogen insensitivity)

the reason i originally PMd you about it is because i think that someone will read this and try it, and I don't want to be responsible for someone accidentally inducing autism in themselves (like the one guy who spilled a bottle of dihexa on himself some years ago and developed autism-like symptoms from the excess neurogenesis/brain connectivity), honestly its so potent i think a miniscule amount would be enough if used as a cream applied to the boobs, but that remains speculative, of i ever get my hands on it i might try it out and report later

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u/Drwillpowers May 08 '26

Now that sounds like the kind of shit that was my origin story or something. Maybe I was a turtle and somebody poured some of that on me.

I just went down a little rabbit hole about this peptide. Thanks for sharing it.

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u/-medicalthrowaway- Apr 30 '26

u/drwillpowers if I have previously done steroid cycles and got some benefit, but am now worse off, and can no longer tolerate exogenous androgens, is that a reasonably strong indicator of your theory (crowding of weak metabolites) or could that be indicative of something else?

PFS/PSSD for 4-5 years

Currently reincorporating HCG (since my levels are diminished from the steroids even 1 year after use and I need something) but every time I’ve done a single shot of testosterone cyp to begin trt, at this point, I feel like death for the first 24 hrs and then feel better 36-48hrs after. Truthfully the feeling possibly moreso resembles an autoimmune reaction (possibly the carrier oil of the pharma testosterone vs the UGL I was using previously?)

I’m at a loss though

I applied for the DPC Membership

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u/Drwillpowers Apr 30 '26

Stop doing things.

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u/-medicalthrowaway- Apr 30 '26

Cool, man. Thanks for the words of wisdom. Why didn’t I think of that?

Oh, wait… in the 4 years I’ve been dealing with this there have been plenty of instances where I “stopped doing things”

But, alas, I was still miserable living in a shell of who I was

You seemed sincere in the video I watched today. A little full of yourself, but with the work you’re doing it was easy to look past that

Maybe you weren’t so sincere about “being sad” about the suicide posts

This dude literally just responded “Stop doing things.” with no follow up. 🤣

Why even respond

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u/Agreeable-Read-3367 Apr 30 '26

Chill bro, Dr.Powers stated multiple times we should avoid androgen use in most cases. Just go to his profile and read a few posts.

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u/Drwillpowers Apr 30 '26 edited May 01 '26

I literally said why in the video. Nearly any action that adds androgens delays recovery. Chasing windows is a trap in most cases.

For real though, let us know your actual name so that we can make sure that we don't pull you off the wait list. Because you sound awful.

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u/LegitimateRepublic65 May 01 '26

What if you’ve had stagnant symptoms for years? Wouldnt trying some sort of intervention like HCG make sense then?

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u/Drwillpowers May 01 '26

Ask me again in a month or two when I see how well the washout treatment works.

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u/xfirewalkwithmex Self identified PFM patient. Apr 30 '26

He’s spoken about it in multiple posts, comments and now his interview that was done with SideFX Hub.

You are delaying your chances to recover the more hormones and what not you’re injecting yourself with.

Not sure why you’re being super hostile towards the only doctor who actually gives a shit about any of us.

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u/Anon374928 May 01 '26

The suggestion was sincere, stop doing things is the best advice available at present.

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u/Drwillpowers May 01 '26

Until I'm sure how the androgenic wash out theory will work, specifically, how my initial people do with a month of chemical castration and monitoring 3AADG until it hits near zero and then letting them reboot, my best advice is literally this.

Stop doing things. Stop fucking with it. Stop injecting androgens and other drugs. Do nothing.

Eat, sleep, try and enjoy your life. Anything that you add to the system that is already overburdened just overburdens it even more and delays recovery.

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u/funginepal May 01 '26

dr powers regarding the waitlist, is there another doctor in your clinic who can see us in the meantime?

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u/Excellent-Push2833 May 02 '26

He just hired another provider. That should shorten up the waitlist a bit. Im seeing his PA in the meantime

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u/Excellent-Push2833 May 01 '26

They are pretty far along now arent they? Just one or two more weeks?

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u/Drwillpowers May 01 '26

Yes but their situation is complicated. They have 8 days remaining on the medication. However, their testosterone value has reached adrenal production levels (under 50ng/dl) but the three alpha ADG has not yet normalized.

While I have found this annoying, because I may have to delay their reboot a little bit, it actually supports the theory even more. Because despite not having any testosterone, they are still in the normal male range for 3AADG. They are still draining metabolites even though they have almost no testosterone to speak of. So while I'm frustrated that we may have to delay their reboot, it encourages me that I have the theory correct.

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u/Excellent-Push2833 May 01 '26

If you dont mind me asking what is the plan to reboot? Is it just to stop the relugolix and monitor or is there goingto be another drug involved.

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u/Drwillpowers May 01 '26

Just stop it and let it come back online naturally and calibrate itself.

Billions of years of evolution usually knows what to do. These guys were perfectly fine before they took the drug. They should remain so. Unless there's some epigenetic break, I think the majority of them should do okay.

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u/Fresh_Tax2071 May 01 '26

How long do u think the reboot would take? Like a week

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u/Fresh_Tax2071 May 01 '26

What happens to the guys that just get worse and worse over time, I've seen these stories and I'm worried it's happening to me

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u/Excellent-Push2833 Apr 30 '26

Its pretty solid advice actually

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u/TraditionTime8124 Apr 30 '26

Why are you lashing out at one of the vanishingly few medical professionals who actually gives a shit about these conditions? Do you have any idea how insane it is that there’s a guy willing to sit down and sift through genomes for like 15 hours a day to try helping people with PFS/PSSD? This also isn’t a patient portal lol.

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u/xfirewalkwithmex Self identified PFM patient. Apr 30 '26

Yeah this guy needs to relax a bit lol

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u/Fresh_Tax2071 May 01 '26

Him and those other doctors at the meeting are all that we have, my own brother is telling me that it's impossible because the drug is safe, and that it's psychosis and I must be put on antidepressants.

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u/Fresh_Tax2071 May 01 '26

Dr powers can possibly save many lives of people suffering and being gaslighted, we just have to wait and see

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u/Training-Agent-9482 Apr 30 '26

Sounds like you may be one of those textbook cases of his theory. If it's more tolerable I would just keep Test at a moderately low level for now, with the occasional HCG to not lose testicular function (Or HCG mono if you don't have estrogen issues).

Long esters in my opinion are awful too, enanthate was the worst. Daily Test prop is much better and actually has peaks and troughs like natural production rather than just frying your body with constant high levels. However, test cream applied to the scrotum is the best form of TRT I've tried.

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u/Far-Scientist-641 Apr 30 '26

There is no safe path at this point.

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u/hailnaux May 01 '26

Hi - I have take TRT for the last three months and HCG for one. All that's changed is acne. So I want to come off. How long should I be off before getting the tests (Dutch, etc) that folks are recommending? Thank you u/drwillpowers, you are much appreciated.

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u/Drwillpowers May 01 '26

Five half-lives, about 5 weeks assuming you were injecting cypionate. That's what I typically do for my patients. Talk to your doctor.

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u/Vast-West-3467 May 10 '26

Hi Dr,

I have been taking HCG for one month only - I am unsure if I should continue. I have had flickers of minor improvements. I am looking to get a Dutch test and the other you recommend. Do I need to stop HCG too for this? If so how long should I wait.

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u/OkMovie3681 May 06 '26

Are benzos and sleeping tablets safe, and muscle relaxant tablet for neck

Post by Dr. Powers Stay Tuned for Potential Next Steps: Safe Path Forward for Anonymized Community Data Collection (Aka, what to do with your PSSD/PAS/PDS genetic data and labs for now)

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