Endocrine Abstracts

JOINT869

Background: Testosterone replacement therapy (TRT) in Klinefelter syndrome (KS) is associated with reduced mortality. A potential mechanism behind this could be overall positive effects of TRT on metabolism in KS.

Aim: We investigated whether TRT in KS was associated with risk of type 2 diabetes (T2DM) as a proxy for metabolism.

Methods: We conducted a cohort study with riskset sampling based time of TRT in KS. Using Danish registry data, we estimated the risk of T2DM in KS. We computed the cumulative incidence and hazard ratios (HR) for incident T2DM in KS at three different life-stages: a) undiagnosed, b) diagnosed with no TRT, and c) diagnosed with TRT. We also included a male population control group. Lastly, we evaluated hemoglobin A1c levels (HbA1c) at diagnosis of T2DM and after two years of living with T2DM.

Results: We studied 895 men with KS and 50,110 controls from January 1994 until December 2022. The incidence of T2DM in KS was not associated with diagnosis- or TRT status (P >0.2). The overall risk of T2DM was increased in KS at all life-stages compared with controls (P < 0.001). Similar data was seen for 5 and 10-year risk of T2DM. Compared with TRT treated KS, the incidence of T2DM was almost 75 % lower among controls (HR (95 CI), 0.27 (0.14-0.52). Maximum levels of HbA1c at diagnosis and lowest obtained values after two years of T2DM were not different among KS life-stages or comparing KS and controls (P >0.2).

Conclusion: The risk of T2DM in KS is increased and not alleviated by TRT. These data indicate that the unfavorable metabolic profile in KS is only to a lesser extend explained by hypogonadism, and that specific genetic alterations as a consequence of the 47,XXY karyotype could contribute substantially to metabolic risk in the patients.