• Patients with CRMPC can safely be treated in clinical trials using high-dose exogenous testosterone
• Patient selection is crucial in this approach, however, because testosterone supplementation may be beneficial for some patients but activate cancer growth in others
• Patients did not, on average, achieve sustained supraphysiologic serum testosterone levels despite receiving three times the usual replacement dose of testosterone
• Future studies should employ strategies to maximize testosterone serum levels, use contemporary methods of identifying patients with androgen receptor overexpression, and utilize PSA Working Group II Consensus Criteria clinical trial endpoints
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