Here, we report two cases of late-onset LHON following hormonal (androgen-suppressing) therapy for prostate cancer, specifically after the introduction of Enzalutamide, an antagonist of androgens’ receptor, in association with Leuprolide, a gonadotropin-releasing hormone (GnRH) analogue. The gene discussed is GNRH1; the disease is Leber hereditary optic neuropathy.