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

Major depressive disorder (MDD) under treatment may be accompanied by residual sexual dysfunction and fatigue. This broadens the differential diagnosis and destabilizes symptom attribution. A 54-year-old Japanese man with MDD formed a late-onset hypogonadism (LOH) hypothesis from online information and self-referred to urology. He was receiving long-term polypharmacy and presented with fatigue, insomnia, arthralgia, and reduced libido. Total testosterone was 2.82 ng/mL, and free testosterone was 5.3 pg/mL. After counseling and informed consent, testosterone replacement therapy (TRT) was initiated with testosterone enanthate 250 mg intramuscularly once monthly. During eight injections, perceived benefit was limited and transient. Erectile difficulty and irritability recurred, and TRT was discontinued. Depressive symptoms persisted, and ongoing medication adjustments were required during TRT. This limited causal interpretation of symptom changes and TRT responsiveness. This case shows that reducing diagnostic reasoning to a binary choice of LOH or MDD can fragment hypothesis updating. From the outset, depressive pathophysiology, medication effects, and the LOH hypothesis should be evaluated in parallel. A shared diagnostic plan with prespecified indicators and discontinuation criteria can preserve diagnostic convergence even under fragmented care.