Prostate Cancer, Gender Identity, and Testosterone Replacement Therapy in Klinefelter Syndrome: A Case Report and Literature Review

Klinefelter syndrome (KS), karyotype 47, XXY, is a common cause of hypogonadism in males. Patients with this condition often experience symptoms of gonadal failure, which can precipitate gender identity challenges. Treatment with testosterone replacement therapy (TRT) can combat these symptoms by improving sexual function, muscle mass, bone health, and virilization, thereby enhancing the quality of life (QOL). Although TRT is often employed in patients with KS, there is a concern that the application of exogenous testosterone may increase the risk of prostate adenocarcinoma development and progression. We report the case of a 58-year-old male with KS who is also diagnosed with prostate adenocarcinoma and wished to remain on TRT post-radiation therapy in support of his gender identity and QOL. We describe the challenges this patient faced when balancing a rising prostate-specific antigen level and risk of cancer recurrence with his QOL.