Supraphysiological androgen levels (SAL) are used in the bipolar androgen therapy in clinical phase trials to inhibit CRPC.<h4>Methods</h4>Co-immunoprecipitation, immunofluorescence, growth and cell senescence assays, mouse xenografted CRPC, AR target gene analyses of organs, analyses of RNA-seq, ChIP-seq and patient-derived xenografts, qRT-PCR, 3D tumor spheroids, knockdown experiments.<h4>Results</h4>Both AR-antagonists and -agonist at SAL induce cellular senescence despite acting oppositely on AR transcriptional activity. The gene discussed is AR; the disease is neoplasm.