The Chronic Thermal Stress Model of Androgenetic Alopecia: A Unified Environmental–Vascular–Molecular Hypothesis

This paper presents the Chronic Thermal Stress Model (CTSM) of Androgenetic Alopecia (Version 5.0) — an independent research hypothesis proposing that DHT acts primarily as a metabolic activator of brain centres at puberty, elevating cerebral heat output that creates chronic thermal stress in the anatomically vulnerable vertex scalp. The model identifies a unified molecular mechanism in which both DHT (via DKK1) and perifollicular hypoxia (via HIF-1α) independently suppress the Wnt/β-catenin pathway — supported by published transcriptomic data from human AGA tissue. The hypothesis explains AGA topography, pubertal onset, seasonal variation, gender differences, and the partial efficacy of 5-alpha reductase inhibitors, and generates nine empirically testable predictions. The central unresolved empirical question — whether DHT elevation at puberty produces a measurable thermal differential at the vertex skull — is identified as the primary experimental target and can be tested using existing MR thermometry technology.