Re: Cure for PFS
u/drwillpowers
r/DrWillPowers2026-05-02T19:04:19Z
Dr Will Powers’ own statements and theorizing
Summary (paraphrased)
Replying to a commenter theorizing about common denominators among disparate reported PSSD recoveries (a GSK3β-inhibition hypothesis), Powers states there is no single PFS mutation — he has identified on the order of 30, and it is their combination that matters, producing different recovery and crash patterns. He theorizes that an unidentified compound ("LM") may act via NRF2, which interacts with his SLCO/ABCC/UGT2BXX gene set — potentially unmasking the same problem through a different route. He illustrates combinatorial heterogeneity with two patients at identical testosterone (~500 ng/dL): one with near-zero 3a-ADG, one with unmeasurably high 3a-ADG — different deficits, same catastrophe when 5ARI is added. He also notes a roflumilast patient's breakthrough report of dopamine function returning.
Key points (paraphrased)
- Roughly 30 mutations identified; the combination, not any single gene, determines outcome.
- Combinatorial heterogeneity produces different recovery/crash patterns.
- NRF2 proposed as a new interaction node; an unidentified compound ("LM") hypothesized to act through it.
- Worked contrast: identical testosterone with opposite 3a-ADG extremes — same catastrophe from 5ARI.
- Roflumilast patient reported dopamine function returning ("felt like Adderall").
Why it’s in the corpus
The combinatorial genetics model stated quantitatively (~30 loci), explaining GWAS failure. NRF2 enters as a new interaction node, and the identical-T/opposite-3a-ADG contrast is the sharpest illustration of why single-marker diagnostics fail.
Context — the post Powers was replying toVerbatim third-party text, shown for context only — not Powers’ statement. Usernames removed.ShowHide
Powers' comment replies to [username removed], who asked about common denominators — possibly GSK3β inhibition — among disparate self-reported PSSD recoveries (SSRI reinstatement/switching, inositol, cyproheptadine rebound, etc.), in a thread where the OP posted test results after 20 years of Zoloft and PSSD onset during taper.
(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.
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