This therapeutic model is anchored in molecular evidence linking estradiol signaling to neurotrophic induction (e.g., BDNF), inflammatory attenuation (via IL-6 and TNF-α suppression), and HPA axis recalibration—core pathways dysregulated across affective, cognitive, and stress-responsive domains in male BD (9, 32, 35). Here, TNF is linked to Behcet disease.