BACKGROUND Men with Klinefelter syndrome (KS) develop hypergonadotropic hypogonadism, are in need of testosterone replacement therapy (TRT) and present with a more than fourfold increased risk of thrombosis. TRT in KS has the potential to modify thrombotic risk, but data are scarce. AIM To assess effects of 18 months TRT on hemostasis in KS and identify genes associated with the prothrombotic phenotype. METHODS Untreated and TRT treated men with KS were included at baseline and matched to healthy controls. TRT was initiated in untreated KS and all groups were re-assessed after 18 months follow-up. Thrombin generation was evaluated with or without thrombomodulin, and fibrin clot lysis was evaluated by turbidity measurements. RNA expression was assessed in blood, fat and muscle tissue of TRT treated KS and controls. RESULTS Thrombin generation with thrombomodulin was slightly increased in untreated KS, but overall KS was not associated with a hypercoagulable state. KS presented with fibrinolytic impairment associated with higher body fat and higher levels of fibrinogen. Eighteen months TRT in KS was associated with a reduction in body fat and fibrinogen, attenuating the prothrombotic profile. The expression of ENPP4 was higher in men with KS, and served as a key player among a group of genes associated with impaired fibrinolysis. CONCLUSIONS KS is associated with a specific expression profile contributing to fibrinolytic impairment and increased thrombotic risk in the patients. TRT in KS has potential for alleviating the prothrombotic phenotype, in particular by reducing body fat and fibrinogen. CLINICAL TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT02526628, Registered August 18, 2015.

中文翻译：

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Klinefelter 综合征的睾酮替代疗法 - 止血和 RNA 表达相关的后续研究。

背景 患有克兰费尔特综合征（KS）的男性会出现高促性腺激素性性腺功能减退症，需要睾酮替代疗法（TRT），并且血栓形成的风险增加四倍以上。堪萨斯州的 TRT 有可能降低血栓风险，但数据很少。目的 评估 18 个月 TRT 对 KS 止血的影响，并鉴定与血栓前表型相关的基因。方法 将未经治疗和 TRT 治疗的 KS 男性纳入基线，并与健康对照相匹配。在未经治疗的 KS 中开始 TRT，并在 18 个月随访后重新评估所有组。在有或没有血栓调节蛋白的情况下评估凝血酶的生成，并通过浊度测量评估纤维蛋白凝块的溶解。对 TRT 治疗的 KS 和对照的血液、脂肪和肌肉组织中的 RNA 表达进行了评估。结果 在未经治疗的 KS 中，血栓调节蛋白的凝血酶生成略有增加，但总体 KS 与高凝状态无关。KS 表现为与较高的身体脂肪和较高水平的纤维蛋白原相关的纤溶障碍。KS 中 18 个月的 TRT 与体内脂肪和纤维蛋白原的减少有关，从而减弱了血栓形成的情况。ENPP4 在患有 KS 的男性中表达较高，并且是一组与纤维蛋白溶解受损相关的基因中的关键角色。结论 KS 与导致患者纤溶损伤和血栓形成风险增加的特定表达谱相关。堪萨斯州的 TRT 具有缓解血栓前表型的潜力，特别是通过减少体脂和纤维蛋白原。临床试验注册号 ClinicalTrials.gov NCT02526628，2015 年 8 月 18 日注册。