Re: Questions regarding current PFS theory
u/drwillpowers
r/DrWillPowers2026-04-18T08:57:02Z
Dr Will Powers’ own statements and theorizing
Summary (paraphrased)
Answering questions about variable onset and post-cessation crashes, Powers gives three linked explanations. First, milder or slower onsets reflect fewer defects — it takes longer to reach threshold. Second, people who crash on quitting had upregulated compensatory enzymes while on the drug and encoded that state epigenetically, then cannot rewrite the epigenetic state for the drug-free condition — the DVD-R (not DVD-RW) metaphor: stuck in a configuration designed for the drug's presence. Third, the genetic defect persists after metabolites clear, which is why elimination alone doesn't resolve the condition. He adds that inability to achieve windows marks a more severe epigenetic state, and names candidate "stuck" genes recurring in PFS genomes: CREBBP, ARID1A/B, CHD4–9, and HDAC10.
Key points (paraphrased)
- Onset speed scales with defect load — a threshold model of timing.
- Cessation crash = failure to rewrite the drug-adapted epigenetic state (DVD-R vs DVD-RW).
- The genetic defect persists after metabolite clearance, so elimination alone is insufficient.
- Inability to achieve windows indicates a more severe epigenetic state.
- Candidate stuck-genes: CREBBP, ARID1A/B, CHD4–9, HDAC10.
Why it’s in the corpus
Explains variable onset and the post-cessation crash puzzle — two of the most commonly raised objections. Introduces the DVD-R metaphor and the first candidate gene list for the epigenetic-persistence layer.
Context — the post Powers was replying toVerbatim third-party text, shown for context only — not Powers’ statement. Usernames removed.ShowHide
Powers' comment replies to the original post "Questions regarding current PFS theory" by [username removed], who asked about delayed onset, why symptoms often appear only after quitting finasteride, and how non-responders fit the model.
(Parent context recovered from the r.genit.al mirror on 2026-10-09; 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.
Related records
- Video
Dr. Will Powers Interview [PFS / PAS / PSSD Summit 2026]
Dr. Will Powers · SIDEfxHUB - PFS & PSSD Patient Organisation · 21:27 (1287s)
PFS, PAS, PSSD mechanism theory; Powers' unifying model; vulnerability screening
ARARID1ACHD8HDAC10YT-iWFDBRTgT3g2026-04-29PFSPSSDPRSDCore corpus - Powers gene claim
ARID1A; CHD8; HDAC10 — recurring "glitches" (unspecified)
Confidence: interview
In whole-genome sequencing of ~100 PFS patients, glitches in epigenetic monitoring genes — ARID1A, CHD8, HDAC10 — appear "more than they should" statistically. Epigenetic flags (e.g., for AR upregulation) may fail to be removed after drug discontinuation.
ARARID1ACHD8HDAC10PGL-ARID1A-CHD8-HDAC102026-04-29PFSCore corpus - Powers · Reddit commentCurated Powers pick
Re: Im going to be taking the week off next week to…
u/drwillpowers · r/DrWillPowers
Replying to a post-letrozole case with PFS-identical symptoms (a Klinefelter patient), Powers frames PFS and PSSD as the same mechanism in different flavors — inborn metabolic error plus drug, with recovery blocked by an epigenetic glitch — and notes…
ARID1AHDAC10KDM6APRH-15042026-04-19T00:13:31ZPFSPSSDPowers Reddit history