Self-Referred Late-Onset Hypogonadism Hypothesis and Testosterone Replacement Therapy in Major Depressive Disorder Under Polypharmacy: A Case Report

    February 2026 in “ Cureus ”
    Kenta Ichino, Nobuo Okui, Hisamitsu Ide, Shigeo Horie
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    TLDR Testosterone therapy had limited benefits for a man with depression and suspected low testosterone, highlighting the need for careful diagnosis and treatment planning.
    A 54-year-old Japanese man with major depressive disorder (MDD) and symptoms of fatigue, insomnia, arthralgia, and reduced libido hypothesized late-onset hypogonadism (LOH) and self-referred for testosterone replacement therapy (TRT). Despite eight monthly injections of testosterone enanthate, benefits were limited and transient, with recurring erectile difficulty and irritability, leading to discontinuation of TRT. The case highlights the complexity of diagnosing LOH versus MDD, emphasizing the need for parallel evaluation of depressive pathophysiology, medication effects, and LOH. A shared diagnostic plan with clear indicators and discontinuation criteria is recommended to maintain diagnostic clarity in fragmented care.
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