Our previous studies in PCa revealed that estrogen signaling and hypoxia signaling act synergistically in regulating gene transcription towards an aggressive phenotype, from a mechanistic point of view, by forming a combinatorial complex with endothelial Nitric Oxide Synthase/Estrogen Receptor β/Hypoxia-Inducible Factor 2 Alpha (eNOS/ERβ/HIF-2α) on the promoter of target genes [21,22,23,24]. This evidence concerns the gene EPAS1 and posterior cortical atrophy.