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Klinefelter syndrome and testosterone treatment: a national cohort study on thrombosis risk.

ABSTRACT: Objectives:Klinefelter syndrome (KS), 47,XXY, can be viewed as a disease model for investigating the risk of thrombosis in male hypogonadism and the subsequent risk related to testosterone treatment. We describe rates of thrombotic risk factors, thrombosis and thrombosis mortality in KS and the association with testosterone treatment. Methods:National registry-based matched cohort study with follow-up from 1995 to 2016 set in Denmark. For the study, 1155 men with KS were each matched by year and month of birth to 100 men from the background population. First thrombotic events and thrombosis mortality was evaluated by event rates and hazard ratios (HRs) and by applying testosterone treatment as a time-dependent covariate. Results:The KS cohort had higher incidence of venous thromboembolism relative to the comparison cohort (HR, 3.95; 95% CI, 2.83-5.52). Total thrombotic deaths were increased in KS (HR, 1.76; 95% CI, 1.18-2.62), and all-cause mortality was increased in KS following arterial thrombosis (HR 1.73; 95% CI 1.22-2.47). Only 48.7% of men with KS redeemed prescriptions for testosterone. Untreated men with KS were on average born 12 years before those treated, and the majority of untreated men with KS with available biochemistry were hypogonadal. Testosterone treatment in KS was associated with a non-significant decrease in venous thromboembolism and thrombotic deaths. Conclusion:Thrombosis and thrombotic deaths are increased in KS. Only half of the men with KS ever received testosterone treatment, despite overt hypogonadism in the non-treated. Testosterone treatment in Klinefelter syndrome was insignificantly associated with lower incidence rates of venous thrombosis and thrombotic deaths.

SUBMITTER: Chang S

PROVIDER: S-EPMC6993257 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Klinefelter syndrome and testosterone treatment: a national cohort study on thrombosis risk.

Chang Simon S Christiansen Christian Fynbo CF Bojesen Anders A Juul Svend S Münster Anna-Marie B AB Gravholt Claus H CH

Endocrine connections 20200101 1

<h4>Objectives</h4>Klinefelter syndrome (KS), 47,XXY, can be viewed as a disease model for investigating the risk of thrombosis in male hypogonadism and the subsequent risk related to testosterone treatment. We describe rates of thrombotic risk factors, thrombosis and thrombosis mortality in KS and the association with testosterone treatment.<h4>Methods</h4>National registry-based matched cohort study with follow-up from 1995 to 2016 set in Denmark. For the study, 1155 men with KS were each matc ...[more]

PMID: 31829966

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Project description:Klinefelter syndrome (KS, 47,XXY) is the most common sex chromosome aneuploidy in males. A variety of complex clinical needs is associated with KS, including physical, cognitive and psychosocial impairments. Standard treatment for KS consists of androgen replacement therapy in adolescence to offset testosterone deficiency. Such treatment has a beneficial effect on the physical and behavioral manifestations of this syndrome. Whether androgen supplementation has a significant influence on the brain, however, is unknown. In the current study, we examined regional gray matter volume in boys with KS to assess whether treatment with oxandrolone, a synthetic hormone analog of testosterone, was associated with structural changes in the brain. Specifically, we focused our investigation on the hippocampus, given (1) its involvement in KS, and (2) the high concentration of androgen receptors found in this region. Structural magnetic resonance imaging data was acquired from a subsample of boys who completed a 2-year double-blind clinical trial in which patients were randomized to treatment with oxandrolone or to placebo, as well as from a sample of typically developing (TD) boys. Group differences in hippocampal volume were examined. A significant main effect of group was observed. Pairwise comparisons indicated smaller hippocampal volume in the placebo group relative to the oxandrolone group, as well as smaller volume in the placebo group relative to the TD control group. No difference in volume was observed between the treatment and TD groups. Moreover, across KS subgroups, a significant positive association was observed between hippocampus volume and performance on a spatial memory task, indicating treatment-based changes in brain structure may underlie cognitive change. These findings confirm prior reports implicating a role of the hippocampus in KS and are important in extending previous research by demonstrating a significant effect of androgens on brain structure.

Dataset Information

Klinefelter syndrome and testosterone treatment: a national cohort study on thrombosis risk.

Publications

Klinefelter syndrome and testosterone treatment: a national cohort study on thrombosis risk.

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