Evaluation of the Efficacy of Transdermal and Injection Testosterone Therapy in Klinefelter Syndrome: A Real-Life Study

CONTEXT: Klinefelter Syndrome (KS) is the most frequent sex chromosome disorder in males. Due to hypergonadotropic hypogonadism, treatment with testosterone replacement therapy (TRT) is commonly indicated. There are no international guidelines for the most appropriate TRT in KS. OBJECTIVE: We aimed to evaluate how different routes of testosterone administration impact testosterone-responsive variables, as well as the development of later metabolic diseases and other complications. METHODS: We conducted a retrospective study covering 5 years from 2015 to 2020. Data on TRT, biochemical parameters, bone mineral density (BMD), medications, comorbidity, and karyotyping were derived from electronic patient records and The Danish Cytogenetic Register. RESULTS: A total of 147 KS males were included: 81 received injection TRT, 61 received transdermal TRT, and 5 did not receive TRT. Testosterone levels were similar in the 2 TRT groups (P = 0.9), while luteinizing hormone and follicle-stimulating hormone levels were higher in the group receiving transdermal TRT (P = 0.002). Levels of cholesterol, blood glucose, hemoglobin A1c, hemoglobin, hematocrit, liver parameters, prostate-specific antigen, and spine and hip BMD were similar in the 2 treatment groups (Ps > 0.05). CONCLUSION: TRT, irrespective of route of administration, affects androgen-responsive variables similarly in males with KS. Neither long-acting injection nor transdermal gel seem to reduce the risk of metabolic diseases significantly. These results should encourage clinicians in seeking the route of administration resulting in the highest degree of adhesion to treatment based on individual patient preferences. Implementation of shared decision-making with patients may be important when choosing TRT.