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Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus N, Denmark
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Department of Molecular Medicine, Aarhus University Hospital, Aarhus N, Denmark
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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.
Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Internal Medicine, Lillebaelt Hospital, Kolding, Denmark
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Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark
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Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark
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Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark
Department of Haematology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
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Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
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Department of Clinical Biochemistry, Hospital of South West Jutland, Esbjerg, Denmark
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Objective
Klinefelter syndrome (KS) is associated with increased risk of thrombosis. Hypogonadism and accumulating body fat in KS have a potential impact on fibrinolysis. In this study, we assessed the fibrinolytic system and the association with testosterone levels in KS.
Design
This study is a cross-sectional comparison of men with KS and age-matched male controls.
Methods
Fibrin clot lysis was evaluated by turbidity measurements and by measuring levels of individual fibrinolytic proteins in plasma samples. Fibrin clot structure was evaluated by scanning electron microscopy. Total testosterone was measured by liquid chromatography-tandem mass spectrometry. Body fat was evaluated by dual-energy X-ray absorptiometry.
Results
In this study, 45 men with KS and 45 age- and education-matched controls were included. Men with KS had a 24% reduction in fibrin clot lysis compared with controls (46.2 ± 17.1 vs 60.6 ± 18.8 %/h, P = 0.0003) and higher levels of fibrinogen, factor XIII (P ≤ 0.01), and plasminogen activator inhibitor type 1 (P = 0.04). Men with KS had lower total testosterone (P = 0.008) and higher body fat (P = 0.001). In KS, reduced fibrin clot lysability was associated with higher fibrinogen and body fat related to decreasing total testosterone and hypogonadism among men with KS. Fibrin clot structure was not different compared to KS and controls.
Conclusions
Fibrin clot lysis in KS was markedly reduced, potentially contributing to a prothrombotic state and increasing thrombotic risk. Hypogonadism in KS was associated with increased fibrinogen and total body fat, predicting reduced fibrin clot lysis.
