3α-HSD (3α-hydroxysteroid oxidoreductase/dehydrogenase; encoded by AKR1C2/AKR1C4) — upregulated (acquired)
Confidence: direct2026-09-14
Dr Will Powers’ own statements and theorizing
Powers’ claim (paraphrased)
Upregulated 3α-HSD acts as the enzymatic bridge overproducing downstream metabolites (3α-androstanediol, 3α-ADG) and, critically, cerebral THDOC — a GABA-A positive allosteric modulator. Chronic excess remodels downstream neural networks (benzodiazepine analogy), producing the anhedonia/low-libido phenotype.
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
AKR1C1; AKR1C2; AKR1C3; AKR1C4 — defects (unspecified)
Confidence: direct
Defects in AKR1C enzymes can contribute, but their products are mostly cleared via glucuronidation — so a bad glucuronidation enzyme (UGT2B1X) is the more fundamental defect. AKR1C enzymes and SRD5A1 are also epigenetically silenceable, and valproic acid may…
AKR1C1AKR1C2AKR1C3AKR1C4SRD5A1PGL-AKR1C1-AKR1C2-AKR1C3-AKR1C4circa May 2026PFSCore corpus - Powers · Reddit post
Untitled long-form research update — new model of PFS/PSSD/post-drug syndromes (Sept 2026)
u/drwillpowers · r/DrWillPowers
Powers revised his model: the anhedonia/low-libido subtype of PFS/PSSD is driven by pathological EXCESS — not deficiency — of neurosteroids such as THDOC and androsterone that positively modulate GABA-A, causing downstream neural network remodeling…
DWP-0022026PFSPSSDCore corpus