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Metabolic Effects of Androgen-associated Body Mass in Klinefelter Syndrome

Ehrhart MD, Guthrie IR, Qeadan F, Burge MR

Patients with Klinefelter Syndrome (KS) are at increased risk for both diabetes and cardiovascular disease. While the anabolic effects of androgen replacement therapy may be associated with weight gain in such patients, the metabolic effects of this weight gain are unknown. Since untreated KS represents a natural example of androgen deprivation, we hypothesized that KS patients who are receiving androgen replacement would have a healthier metabolic risk factor profile, in addition to an increased Body Mass Index (BMI), relative to patients who are not receiving androgen replacement.

Using de-identified data collected from Health Facts (a national, consolidated, and relational database of Electronic Health Records), we identified 2,447 adult patients with an ICD-9 billing code for KS. Of these, 262 patients were included in this study based on available anthropometrics, metabolic profiles, and information about androgen replacement. Multiple linear regression analysis was performed using BMI as the dependent variable in a model that included age, androgen replacement therapy (yes or no), A1C, blood pressure, and fasting lipids. Post-hoc comparisons were made using frequency analysis and the unpaired Student’s t-test.
There were 81 patients with KS who received androgen replacement and 181 patients who did not. In multiple regression, only androgen therapy was positively and significantly associated with BMI while adjusting for other risk factors (p=0.03). Post-hoc comparison of metabolic risk factors revealed no other differences between patients who received androgen replacement and those who did not. These data suggest that androgen replacement therapy in Klinefelter Syndrome is associated with increased BMI, but this increase does not appear to exert a detrimental effect on other metabolic risk factors in this condition.