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

Abstract

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.

Clinical features and prevalence of Klinefelter syndrome in transgender individuals: A systematic review

“…Pathognomonic small testicular volume was reported in two individuals 37,44 . Two individuals had venous thromboembolic events before the initiation of estradiol 40,41 . Of the two case reports that reported on semen analysis, both had azoospermia 37,38 .…”

“…Of the seven case studies that reported serum testosterone concentration, five (71%) had serum testosterone concentrations below the lower limit of the male reference range. In all, seven articles reported on the prescription of testosterone therapy in nine individuals, 31,37,38,40,41,44,45 three of whom had poor compliance or ceased testosterone following the development of secondary male sex characteristics 41,44,45 . One individual ceased testosterone therapy after days, 38 while another ceased while receiving treatment for prostate cancer 40 .…”

“…In all, seven articles reported on the prescription of testosterone therapy in nine individuals, 31,37,38,40,41,44,45 three of whom had poor compliance or ceased testosterone following the development of secondary male sex characteristics 41,44,45 . One individual ceased testosterone therapy after days, 38 while another ceased while receiving treatment for prostate cancer 40 . Two individuals reported an improvement in gender incongruence following the commencement of testosterone 40,43 .…”

“…One individual ceased testosterone therapy after days, 38 while another ceased while receiving treatment for prostate cancer 40 . Two individuals reported an improvement in gender incongruence following the commencement of testosterone 40,43 . Feminizing hormone therapy was prescribed in seven individuals 31,36,39,41,42,44 …”

Current National and International Guidelines for the Management of Male Hypogonadism: Helping Clinicians to Navigate Variation in Diagnostic Criteria and Treatment Recommendations

“…Indeed, among men with congenital MH, the occurrence of PCa during T treatment is so vanishingly rare that we have been able to identify less than 10 published reports [49].…”