Re: The Problems with the Theory of Impaired Androgen Signaling caused by Metabolite Accumulation: A Peaceful Challenge to Dr. Powers’ Thesis
u/drwillpowers
r/DrWillPowers2026-09-19T16:47:47Z
Dr Will Powers’ own statements and theorizing
Mentions treatments or doses — not guidance
Summary (paraphrased)
Second half of the two-part reply, on scientific openness and testability. Powers says he welcomes challenges and is certainly wrong about parts of his model, describing himself as a clinician learning biochemistry and genetics on the fly; chemical castration trials improved androgenic signaling in every participant so far but didn't resolve all symptoms, showing the model was incomplete. He states his criterion for engaging a challenge: it must be mechanistically rational and testable (a lab test, genetic test, or benign pharmacologic probe like indomethacin) — untestable conjecture is useless. He credits the indomethacin idea to the PSSD patient who proposed it, notes the HIPAA constraint on naming him, and insists his ego will never obstruct revising the model or finding a cure. He also mentions subreddit brigading, the financial interests he believes oppose a cure (PFS coaching businesses, charities, drug-company liability), and a forthcoming funded research study whose findings he intends to publish and use for accountability.
Key points (paraphrased)
- Explicit testability criterion: challenges must propose a mechanistically rational, benign, testable probe.
- Castration trials: androgenic signaling improved in all participants, but incomplete symptom resolution = incomplete model.
- Credits the indomethacin concept to a PSSD patient, not himself.
- Claims financial/industry opposition to solving PFS; funded study in planning.
Why it’s in the corpus
Documents Powers' stated epistemic standards and his admission that the castration trials only partially validate the model — important context for weighting his stronger claims elsewhere in the corpus, and for the corpus's research-ethics/methods notes.
Context — the post Powers was replying toVerbatim third-party text, shown for context only — not Powers’ statement. Usernames removed.ShowHide
Powers' comment replies to u/Drwillpowers:
I"ll try and comment on this more in detail later, but I'll say this much.
Many of the men that I have with PFS actually have had regeneration of their hair while on it.
I now have multiple that have osteopenia or osteoporosis. Indicating that they have had a failure of their normal androgenic signaling or estrogenic signaling.
Ugt2b17 was just one of the first things that I noticed was statistically anomalously common. But, what I've noticed collectively is that there's just disruption in a multitude of different pathways. The amount of different ways that I have seen it be disrupted is crazy. Everything ranging from abcc Gene class stop codons to the inability to make the glucuronide molecule from a deficiency in that specific gene.
Effectively, it is a combination of a multitude of different inborn deficiencies that results in the susceptibility and you're not going to find a statistically significant difference or it would have been found on the gwas studies.
Imagine that you have a thousand people that all have a medical condition. In that group, there are a hundred different ways via 100 different genes to cause the exact same phenotype. A good example of something like this is eye color. There's a lot of different ways to make certain colored eyes.
If you then take 10,000 people, and you look at that group and you trying to determine what the cause is of blue or pink or whatever colored eyes, you're going to struggle, because you're not going to find a statistically significant difference among all of them that stands out unless you happen to land on the most common specific gene. This is what is happening to the hEDS studies.
They continue to do these gwas studies on heds, and they don't find shit. Or they find some really really obscure new version of EDS that only was picked up because they had a ridiculously large sample size but it still doesn't explain the overwhelming majority of that phenotype. (I have a consistent theory on hEDS and […]
(Parent context recovered from the r.genit.al mirror on 2026-10-07; Powers' comment text itself is from John's user-provided export.)
Some fields on this page come from the release’s Markdown edition, which carries text the JSON edition omits.
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