Re: Had another random pssdpfs thought about the…
u/drwillpowers
r/DrWillPowers2026-04-01T15:22:34Z
Dr Will Powers’ own statements and theorizing
Summary (paraphrased)
Reply to a community member's glucuronidation-theory thought about sulfation labs. Powers notes the discussed factor interacts with androgen production and ABCC-family transporters (he believes ABCB1 specifically, with the caveat that he read it long ago). His stated theory: anything that increases androgenic load, disrupts steroid transport, or impairs glucuronidation or other excretion mechanisms can cause the syndrome in someone with pre-existing dysfunction — UGT2B17, UGT2B15, UGT2B7, ABCC defects, or LRP2 — because intracellular sex steroids rise until the metabolite load overwhelms the cell's ability to register normal androgen signaling, "crowded out" by ineffective androgens. Many different compounds could do this, but only in the right person; it cannot happen on a default human genome without built-in dysfunctions.
Key points (paraphrased)
- Trigger generality: any compound raising androgenic load, impairing transport, or impairing excretion can trigger the syndrome given underlying dysfunction.
- Named susceptibility genes: UGT2B17/2B15/2B7, ABCC family, LRP2.
- Mechanism: intracellular steroid overcrowding drowning out normal androgen signaling.
- Requires pre-existing dysfunction; not inducible in a default genome.
Why it’s in the corpus
Generalizes Powers' model beyond finasteride to any androgen-load or excretion-impairing trigger, with an explicit susceptibility-gene list — useful for the corpus's gene–drug interaction framing and for comparing trigger diversity across PFS/PSSD cases.
Context — the post Powers was replying toVerbatim third-party text, shown for context only — not Powers’ statement. Usernames removed.ShowHide
Powers' comment replies to a community member:
Interesting post. I came here from the PSSD subreddit.
Wondering. What's your opinion on Ashwagandha causing a condition that is very similar to PSSD/PFS? There is a whole sub for that as well. r/AshwagandhaSyndrome
(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.
Related records
- Powers · Reddit post
I think I have figured out at least one specific phenotype of PFS, and it is different from the "allopregnanolone" theory
u/drwillpowers · r/DrWillPowers
Powers' key genetics-first post: he proposed a specific PFS phenotype whose "base, core defect" is defective UGT2B17, disabling testosterone's main glucuronidation exit pathway. Carriers show shockingly low 3α-androstanediol glucuronide and near-zero urinary…
AKR1C1AKR1C2AKR1C3AKR1C4HSD17B2+3DWP-0032026PFSCore corpus - Powers gene claim
UGT2B15; UGT2B7 — defective (minor)
Confidence: direct
Defects in these secondary glucuronidation enzymes can compound the UGT2B17 defect, further reducing testosterone exit capacity.
UGT2B15UGT2B17UGT2B7PGL-UGT2B15-UGT2B7circa May 2026PFSCore corpus - Powers · Reddit commentCurated Powers pick
Multi-hit model: a glucuronidation defect alone is necessary but not sufficient
u/drwillpowers · r/DrWillPowers
Replying to [username removed]'s question about why East Asian populations — with roughly 60–70% homozygous UGT2B17 deletion prevalence — don't show higher PFS rates, Powers states that glucuronidation failure alone is insufficient: it was merely the first…
LRP2UGT2B17PRH-15002026-04-14T13:22:58ZPFSPowers Reddit history