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During CRPC development, the tumor undergoes several adaptions counteracting supraphysiological androgen levels, including increased androgen synthesis, AR amplification, AR mutation, AR alternative splicing, MYC overexpression, and hyperactive STAT signaling [113,178,183,184]

This mechanical effect complements the central nervous system effects, providing multiple reinforcing signals that reduce total food intake without requiring conscious effort

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For eight of these nine biomarkers, a majority of subjects in the treatment group recorded values indicating that levels of oxidative stress had fallen