Category: disease_cascade
Androgenetic alopecia (AGA, male + female pattern hair loss) is the most common hair-loss disorder, driven by androgen-mediated follicular miniaturization in genetically susceptible scalp follicles. Pathogenesis: scalp follicles express androgen receptors + type-2 5α-reductase (SRD5A2) → testosterone → 5α-dihydrotestosterone (DHT). DHT binds AR → IGF-1 / dickkopf / TGF-β follicular signaling → progressive anagen-phase shortening + miniaturization (terminal → vellus). Hereditary: AR locus variants (X-linked) + autosomal gene polymorphisms. Therapeutics: (1) Minoxidil (topical 2/5% + oral low-dose 0.625–5 mg) — ATP-sensitive K⁺ channel opener (KATP); vasodilation + direct follicular keratinocyte stimulation; converts vellus to terminal hairs; reversible on discontinuation. Original use: HTN (oral 10–40 mg/d); hypertrichosis side effect → repurposed topical 1988. Low-dose oral revival (LDOM) since 2020 — comparable efficacy with better adherence. (2) Finasteride (oral 1 mg) — SRD5A2 inhibitor → ↓DHT 60–70% scalp + serum; well-established efficacy + safety; sexual side-effect signal + post-finasteride syndrome controversy. Topical finasteride alternative (lower systemic exposure). (3) Dutasteride (oral 0.5 mg) — pan-5αR (SRD5A1+2) inhibitor → ↓DHT >90%; more efficacious than finasteride but off-label for AGA in US. (4) Anti-androgens — spironolactone (off-label oral; female AGA — competitive AR antagonist + ↓adrenal androgen synthesis); cyproterone (EU). Cross-links: [[aromatase_androgen_receptor_axis]] (AR signaling upstream), [[steroid_hormone_biosynthesis]] (DHT synthesis).