AKR1C1; AKR1C2; AKR1C3; AKR1C4 — defects (unspecified)
Confidence: directcirca May 2026
Dr Will Powers’ own statements and theorizing
Mentions treatments or doses — not guidance
Powers’ claim (paraphrased)
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 reverse that silencing.
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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
3α-HSD (3α-hydroxysteroid oxidoreductase/dehydrogenase; encoded by AKR1C2/AKR1C4) — upregulated (acquired)
Confidence: direct
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…
AKR1C2AKR1C4PGL-3alpha-HSD-3alpha-hydroxysteroid-oxidoreductase-dehydrogenase-encoded-by-AKR1C2-AKR1C42026-09-14PFSPSSDCore corpus - Powers gene claim
SRD5A1 — epigenetic silencing (acquired, not germline)
Confidence: direct
SRD5A1 (like AKR1C enzymes) can be epigenetically silenced, and valproic acid (an HDAC inhibitor) appears able to reverse this in his patients, with slow normalization over months.
SRD5A1PGL-SRD5A1circa May 2026PFSCore corpus