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Mette Bøgehave Department of Clinical Biochemistry, Hospital South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark
Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark

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Dorte Glintborg Department of Endocrinology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark
OPEN, Open Patient data Explorative Network, Odense University Hospital, Region of Southern Denmark, Odense, Denmark

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Jørgen Brodersen Gram Department of Clinical Biochemistry, Hospital South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark
Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark

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Else-Marie Bladbjerg Department of Clinical Biochemistry, Hospital South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark
Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark

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Marianne Skovsager Andersen Department of Endocrinology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark

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Johannes Jakobsen Sidelmann Department of Clinical Biochemistry, Hospital South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark
Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark

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Introduction

Hypogonadism is prevalent during opioid treatment, and low testosterone concentrations are associated with cardiovascular disease. The effect of testosterone replacement therapy (TRT) on the coagulation system in men with hypogonadism is not clarified. We investigate the effects of TRT on the tissue factor (TF) and contact activation pathways of coagulation in opioid-treated men.

Materials and methods

This was a double-blinded, placebo-controlled study in 37 men with total testosterone < 12 nmol/L randomized to 24 weeks of testosterone injections (n = 17) or placebo (n = 20). Variables of the coagulation system were analysed at baseline and after 24 weeks. Measurements included the TF pathway (endogenous thrombin potential (ETP) and peak thrombin), the contact activation pathway (endogenous kallikrein potential (EKP) and peak kallikrein), coagulation factors (FVII, FX, prothrombin, and FXII), and inhibitors (tissue factor pathway inhibitor (TFPI), protein C, protein S, antithrombin, and C1 esterase inhibitor (C1inh)). Between-group differences at 24 weeks were determined with analysis of covariance. Within-group changes in TRT and placebo were analysed with paired t-test.

Results

Between-group differences at 24 weeks were observed for ETP (P = 0.036), FVII (P = 0.044), FX (P = 0.015), prothrombin (P = 0.003), protein C (P = 0.004), and protein S (P = 0.038). Within the TRT group, ETP, peak thrombin, FVII, FX, prothrombin, TFPI, protein C, FXII, and C1inh decreased and protein S increased (all P < 0.05). Within the placebo group, coagulation outcomes were unchanged.

Conclusion

TRT affects the coagulation system in an anticoagulant direction through suppressed TF pathway in men with opioid-induced hypogonadism.

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