Glossary

A DHT metabolite that was ELEVATED in PFS plasma while downstream calming neurosteroids stayed low — interpreted in the corpus as a metabolic 'backlog' signal consistent with blocked or rerouted androgen metabolism.

Enzyme family interconverting DHT with androstanediol and DHP with allopregnanolone — the on/off switch for GABA-active neurosteroids. Powers implicates UPREGULATED 3-alpha-HSD in his 2026 neurosteroid-excess model (DWP-002).

The enzyme family converting testosterone to dihydrotestosterone (DHT) and progesterone to dihydroprogesterone; it is also required for neurosteroid synthesis in the brain. Finasteride and dutasteride inhibit it, which is why the corpus treats 5AR blockade as the pharmacological starting point of PFS.

Drug class comprising finasteride and dutasteride, which block 5-alpha-reductase. The corpus's PFS literature concerns persistent effects after 5ARI discontinuation; FDA labeling (2012) notes sexual side effects may persist.

A parallel reductase pathway that tones hormones down for excretion and is essential for bile acid production. Discussed in the 'Rethinking Reductase' video as the overlooked counterpart to 5-alpha-reductase in hormone clearance.

A serotonin autoreceptor whose desensitization/downregulation is a leading mechanistic hypothesis for PSSD, alongside epigenetic changes and hormonal shifts.

Aldo-keto reductase enzymes that include 3-alpha-HSD isoforms and act downstream of 5-alpha-reductase in neurosteroid synthesis. Powers' original PFS theory (DWP-001): only people carrying decreased-function AKR1C variants develop PFS when 5AR is blocked, which would explain the syndrome's rarity.

A progesterone-derived neurosteroid (made via 5-alpha-reductase and 3-alpha-HSD) that positively modulates GABA-A receptors, producing calming, anti-anxiety and antidepressant effects. The corpus uses it in two conflicting ways: Melcangi's CSF studies (PFS-004, PFS-005) and Powers' early theory (DWP-001) frame PFS as allopregnanolone DEFICIENCY, while Powers' 2026 revision (DWP-002) frames the anhedonic PFS/PSSD subtype as neurosteroid EXCESS — track which model a source means.

The nuclear receptor through which testosterone and DHT drive gene expression. The corpus reports it as OVEREXPRESSED in PFS penile skin (SIDE-009) and links AR gene CAG/GGN repeat variants to symptom patterns (PFS-007) — a compensatory upregulation that may paradoxically silence signaling when weak metabolites crowd the receptor.

A glucuronic-acid-conjugated DHT metabolite measurable in blood, used as a marker of androgen metabolism and excretion. One of the three tests in Powers' PFS biomarker battery (with morning hormone panel and DUTCH).

A 5-alpha-reduced androgen metabolite that also modulates GABA-A receptors. Named alongside THDOC in Powers' neurosteroid-excess model of the anhedonic PFS/PSSD subtype.

The inability to feel pleasure. In Powers' 2026 model it defines one of two PFS/PSSD subtypes — the neurosteroid-excess, low-libido/anhedonic subtype — as distinct from the androgenic-signal-loss subtype.

Abnormally high androgen-receptor levels found in PFS penile-skin tissue versus controls (1,446 genes over-expressed overall). Interpreted as a compensatory — and possibly epigenetically locked — response to impaired androgen signaling.

Chromatin-remodeling/epigenetic-regulator genes that Powers reports recurring across PFS patient genomes in his summit interview — offered as candidate genetic-susceptibility loci for post-drug syndromes, pending formal publication.

Enzyme converting testosterone to estradiol. Relevant because PFS cerebrospinal fluid showed increased estradiol alongside decreased DHT, indicating the steroid pathway is rerouted — not just blocked — after finasteride.

Arizona Sexual Experience Scale: a validated questionnaire measuring sexual dysfunction. Used in Irwig's finasteride follow-up (89% of men met dysfunction criteria) and in PSSD clinical characterization — one of the corpus's standard outcome instruments.

A gut bacterial enzyme that removes glucuronic acid tags, recycling androgens back into circulation instead of letting them be excreted. Powers implicates gut beta-glucuronidase activity in the disrupted androgen excretion of PFS and describes targeting it (e.g., with calcium D-glucarate).

A compressed, machine-readable file format used in bioinformatics to store DNA or RNA sequencing reads aligned to a reference genome. It is the binary, highly compressed equivalent of a SAM (Sequence Alignment Map) text file, allowing for drastically smaller file sizes and faster data processing.

An intravenous synthetic formulation of allopregnanolone approved for postpartum depression. Powers (DWP-001) cited the close resemblance between PFS symptoms and severe postpartum depression — which responds to brexanolone — as support for his early allopregnanolone-deficiency theory.

A polymorphic glutamine-encoding tract in the androgen receptor gene; repeat length tunes receptor activity. In 66 PFS patients, CAG (and GGN) length variants were associated with different symptom patterns — a genetic-susceptibility finding.

A supplement Powers reports using (with indomethacin) to support glucuronidation and lower neurosteroid load in his PFS protocol; patient 'crashes' on it are reinterpreted in his model as withdrawal-like effects rather than treatment failure.

CORPUS-SPECIFIC USAGE (Powers): a temporary period of chemical androgen deprivation used as a DIAGNOSTIC probe — 'unplug the router... do they reboot?' — to distinguish PFS subtypes. Powers reports it reliably restores androgenic signaling in the androgen-signal-loss subtype but not the anhedonic subtype. Not a standard medical term in this sense.

Cerebrospinal fluid sampling (via lumbar puncture) to measure brain neurosteroid levels directly. Melcangi's CSF studies provided the first biochemical evidence of persistent neurosteroid disruption in PFS; Powers has requested CSF mass-spectrometry collaboration to identify overproduced molecules.

In genetics, a deletion is a mutation where a section of DNA is lost or removed during replication. It can range from the loss of a single nucleotide base to an entire piece of a chromosome, severely altering genetic code and protein function.

The direct 5-alpha-reductase product of progesterone and the obligatory precursor of allopregnanolone. Found decreased in PFS patient plasma after finasteride discontinuation (PFS-004, PFS-005), showing the whole downstream neurosteroid chain is disrupted.

An epigenetic mark that silences genes without changing DNA sequence. Central to Traish's 'drug-induced epigenetics' model: finasteride is proposed to trigger lasting methylation changes (e.g., at SRD5A2) that persist after the drug is gone.

Neurotransmitter governing reward and motivation; the corpus proposes serotonergic drugs inhibit dopamine signaling in reward circuits (nucleus accumbens), contributing to anhedonia and sexual dysfunction in PSSD.

A tetracycline antibiotic that Powers implicates as a possible gut-flora trigger route in his PFS model — an example of how non-hormonal drugs enter the post-drug-syndrome story via the gut-steroid axis.

Dried Urine Test for Comprehensive Hormones: a urine panel mapping steroid metabolites and their excretion. Powers reports near-zero urinary androgens on DUTCH in over half his PFS patients — his key evidence for broken androgen excretion — and includes it in his three-test biomarker protocol.

The brain's main inhibitory receptor, positively modulated (activated) by allopregnanolone, THDOC and androsterone. It sits at the center of both corpus models: neurosteroid DEPLETION (early Powers, Melcangi) and neurosteroid EXCESS causing network remodeling like chronic benzodiazepine exposure (Powers 2026).

Loss or severe reduction of genital sensation; a hallmark PSSD symptom also reported in PFS (including a case of isolated penile numbness with normal systemic hormones, DWP-009). Healy's diagnostic criteria treat enduring genital sensory change as a necessary criterion.

A polymorphic glycine-encoding tract in the androgen receptor gene, studied alongside CAG repeats for association with PFS symptom variation.

The conjugation pathway that tags androgens for urinary/biliary excretion — one of the 'lanes' in Powers' '15-lane highway' analogy for testosterone exit pathways. He reports glucuronidation defects as the most common finding in PFS patient genomes.

Enzymes that remove acetyl groups from histones, typically silencing genes. The corpus mentions HDACs two ways: fasting-induced beta-hydroxybutyrate acts as an HDAC inhibitor (patient experiment, DWP-007), and HDAC10 recurs among genes Powers reports in PFS patient genomes.

Chemical changes to the histone proteins around which DNA is wound, altering how accessible genes are. Listed alongside DNA methylation as a lasting epigenetic consequence of endocrine disruption in the PFS model.

Hypothalamic-pituitary-gonadal axis: the hormonal control loop governing sex-hormone production. Discussed in the corpus regarding how drugs (and proposed interventions like fasting or HPTA shutdown) modulate or suppress it.

Hypothalamic-pituitary-testicular/adrenal axis. Patients in the corpus report experiments with extended HPTA shutdown (suppressing endogenous hormone production); one reported a transient full-remission 'window' on testosterone reintroduction followed by a crash.

An NSAID that Powers combines with calcium D-glucarate in his PFS protocol aimed at lowering neurosteroid load; mentioned as part of the intervention arm of his 2026 model.

A high-performance, easy-to-use, interactive tool for the visual exploration of genomic data.

Hormone action that occurs locally within the cell where the hormone is made or metabolized, invisible to blood tests. Powers uses it distinctively: weak androgen metabolites crowd the androgen receptor INSIDE cells ('musical chairs with Helen Keller'), silencing signaling while serum labs look normal — his explanation for why standard blood work misses PFS.

A progesterone-derived neurosteroid found decreased in the cerebrospinal fluid of PFS patients versus controls, part of the broad neurosteroid disruption signature.

Liquid chromatography-tandem mass spectrometry: the precise analytical method used to quantify neurosteroids in cerebrospinal fluid and plasma in the Melcangi PFS studies.

The brain's reward center. Rat studies found persistent paroxetine-induced gene-expression changes here after withdrawal — the strongest preclinical evidence for lasting SSRI effects on sexual-reward circuitry.

The proposed field — introduced by Csoka & Szyf (2009) — studying lasting drug-induced epigenetic modifications as a general class of pharmaceutical side effects; the conceptual umbrella under which the corpus groups PFS and PSSD.

A bioinformatics tool that analyzes genetic variants to predict drug response and tailor medical treatment to an individual patient's genetic profile.

Enzyme converting noradrenaline to adrenaline. Giatti et al. (2024) propose PFS and PSSD mechanisms converge here, and the Dr. Rege video notes both finasteride and paroxetine may inhibit it — a candidate shared pharmacological node.

Umbrella term for persistent symptom syndromes that continue after a drug is discontinued — covering PFS, PSSD, post-SSRI syndromes and post-retinoid sexual dysfunction (PRSD). Healy's cross-drug case series (300 cases across drug classes) is the empirical basis for grouping them.

A condition describing persistent sexual, mental, and physical side effects that continue long after stopping finasteride (Propecia or Proscar). Finasteride is widely used to treat hair loss and enlarged prostates. While most users tolerate the drug well, a small subset of individuals report debilitating, long-lasting symptoms.

A condition where sexual side effects (like genital numbness, loss of libido, and erectile dysfunction) persist long after stopping SSRIs. Though the exact cause is unknown, these symptoms can significantly impact quality of life and relationships.

A neurosteroid in the progesterone metabolic pathway, discussed in corpus reviews of neurosteroidogenesis and its disruption by 5-alpha-reductase inhibitors and SSRIs.

Dysfunction of the pudendal nerve supplying the genitals. Melcangi's 2017 study found abnormal pudendal nerve potentials in 4 of 16 PFS patients (DISC-013), the first objective evidence of peripheral neuropathy in the syndrome; at Queen Square the same tests were normal in 8 of 9 PSSD patients with genital sensory loss (CUR-003).

A standard, tab-delimited text format used in bioinformatics to store biological sequence data, like DNA or RNA reads, that have been mapped to a reference sequence. It is the universal language for processing genome sequencing data.

Neurotransmitter targeted by SSRIs/SNRIs; beyond mood, the corpus implicates serotonergic disruption of dopamine, neurosteroid synthesis and gut signaling in persistent post-SSRI dysfunction.

Nerve damage limited to the small nerve fibres (thinly myelinated A-delta and unmyelinated C fibres) that carry pain, temperature and some touch sensation and serve autonomic functions; it can cause numbness, burning or tingling. It is usually shown by skin biopsy, corneal confocal microscopy or thermal threshold testing; nerve conduction studies and somatosensory evoked potentials test large fibres and central pathways, so they can be normal in SFN. In the post-drug syndromes it is proposed as one explanation for genital numbness, and the corpus's evidence is small and mixed: corneal microscopy findings in tiny mixed series (LIT-040, SIDE-002), thermal sensory testing in PSSD (LIT-033), and normal large-fibre tests at Queen Square, where small fibres were not tested (CUR-003). The corpus holds no skin-biopsy study in these syndromes.

Gene encoding 5-alpha-reductase type 1, the isoenzyme expressed broadly including brain and liver. Covered in the systematic review of 5-alpha-reductase isoenzyme biology (PFS-011).

Gene encoding 5-alpha-reductase type 2, dominant in prostate and genital skin. A pilot study found differential SRD5A2 methylation in PFS cerebrospinal fluid versus controls, linking the drug's target gene itself to epigenetic changes.

Gene encoding the third 5-alpha-reductase isoenzyme, less characterized than types 1 and 2 but included in the corpus's systematic review of reductase biology.

A progesterone metabolite found decreased in PFS cerebrospinal fluid, indicating impaired downstream neurosteroid synthesis persisting after finasteride is stopped.

A GABA-A-active neurosteroid derived from deoxycorticosterone. In Powers' 2026 model it is one of the neurosteroids pathologically OVERPRODUCED in the anhedonia/low-libido PFS/PSSD subtype, driving downstream neural network remodeling analogous to chronic benzodiazepine exposure.

Enzymes that attach glucuronic acid to androgens and other steroids so they can be excreted. Powers reports disrupted glucuronidation/excretion — with UGT and ABCC transporter gene findings — as a core defect in his PFS model, leaving weak androgen metabolites to accumulate.

A standard text file used in bioinformatics to store DNA sequence variations. Instead of writing out an entire genome, it only lists where an individual's DNA differs from a standard reference genome.

A tool to predict pharmacogenomic reactions, shared on r/DrWillPowers.

A tool to check for genetic duplications and deletions, shared on r/DrWillPowers.

CORPUS-SPECIFIC patient jargon: a transient period of full symptom remission (the 'window' — e.g., ~2 weeks after testosterone reintroduction) followed by relapse (the 'crash'). Powers' 2026 model reinterprets crashes as withdrawal-like effects from shifting potent-to-weak androgen ratios.