Table_3_Risk of Venous Thromboembolism in Transgender People Undergoing Hormone Feminizing Therapy: A Prevalence Meta-Analysis and Meta-Regression Study.docx

BackgroundAlthough venous thromboembolism (VTE) is a recognized side effect of some formulations of estrogen therapy, its impact in transgender people remains uncertain. The aim of this study was to define pooled prevalence estimate and correlates of VTE in Assigned Males at Birth (AMAB) trans people undergoing gender affirming hormone therapy. MethodsA thorough search of MEDLINE, COCHRANE LIBRARY, SCOPUS and WEB OF SCIENCE databases was carried out to identify suitable studies. Quality of the articles was scored using the Assessment Tool for Prevalence Studies. Data were combined using random effects models and the between-study heterogeneity was assessed by the Cochrane’s Q and I2. ResultsThe eighteen studies included gave information about 11,542 AMAB undergoing gender affirming hormone therapy. The pooled prevalence of VTE was 2% (95%CI:1-3%), with a large heterogeneity (I2 = 89.18%, P<0.0001). Trim-and-fill adjustment for publication bias produced a negligible effect on the pooled estimate. At the meta-regression analysis, a higher prevalence of VTE was significantly associated with an older age (S=0.0063; 95%CI:0.0022,0.0104, P=0.0027) and a longer length of estrogen therapy (S=0.0011; 95%CI:0.0006,0.0016, P<0.0001). When, according to the meta-regression results, the analysis was restricted to series with a mean age ≥37.5 years, the prevalence estimate for VTE increased up to 3% (95%CI:0-5%), but with persistence of a large heterogeneity (I2 = 88,2%, P<0.0001); studies on younger participants (<37.5 years) collectively produced a pooled VTE prevalence estimate of 0% (95%CI:0-2%) with no heterogeneity (I2 = 0%, P=0.97). Prevalence estimate for VTE in series with a mean length of estrogen therapy ≥53 months was 1% (95%CI:0-3%), with persistent significant heterogeneity (I2 = 84,8%, P=0.0006); studies on participants subjected to a shorter length of estrogen therapy (<53 months), collectively produced a pooled VTE prevalence estimate of 0% (95%CI:0-3%) with no heterogeneity (I2 = 0%, P=0.76). ConclusionsThe overall rate of VTE in AMAB trans people undergoing gender affirming hormone therapy was 2%. In AMAB population with <37.5 years undergoing estrogen therapy for less than 53 months, the risk of VTE appears to be negligible. Further studies are warranted to assess whether different types and administration routes of estrogen therapy could decrease the VTE risk in AMAB trans people over 37.5 years subjected to long-term therapy. Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021229916].背景 尽管静脉血栓栓塞症（venous thromboembolism, VTE）是部分雌激素治疗制剂公认的不良反应，但该事件在跨性别人群中的影响仍不明确。本研究旨在明确接受性别确认激素治疗（gender affirming hormone therapy）的出生时被指派为男性（Assigned Males at Birth, AMAB）跨性别者的VTE合并患病率及其相关影响因素。 方法 本研究系统性检索了MEDLINE、考克兰图书馆（Cochrane Library）、Scopus以及科学网（Web of Science）数据库，以筛选符合要求的相关研究。采用《患病率研究评估工具》对纳入文献的质量进行评分。采用随机效应模型（random effects models）合并数据，并通过科克兰Q检验与I²统计量（Cochrane’s Q and I²）评估研究间异质性。 结果 共纳入18项研究，涉及11542名接受性别确认激素治疗的AMAB跨性别者。VTE的合并患病率为2%（95%置信区间：1%~3%），研究间存在显著异质性（I²=89.18%，P<0.0001）。采用修剪填充法（Trim-and-fill adjustment）校正发表偏倚（publication bias）后，合并患病率估计值未发生显著变化。Meta回归（meta-regression）分析显示，较高的VTE患病率与患者年龄更大（S=0.0063；95%CI：0.0022~0.0104，P=0.0027）以及更长的雌激素治疗疗程（S=0.0011；95%CI：0.0006~0.0016，P<0.0001）显著相关。根据Meta回归结果，将分析限定于平均年龄≥37.5岁的研究队列时，VTE的合并患病率升至3%（95%CI：0%~5%），但仍存在显著异质性（I²=88.2%，P<0.0001）；而针对平均年龄<37.5岁的研究队列进行合并分析，VTE的合并患病率为0%（95%CI：0%~2%），无研究间异质性（I²=0%，P=0.97）。针对平均雌激素治疗疗程≥53个月的研究队列，VTE的合并患病率为1%（95%CI：0%~3%），仍存在显著异质性（I²=84.8%，P=0.0006）；而针对雌激素治疗疗程<53个月的研究队列进行合并分析，VTE的合并患病率为0%（95%CI：0%~3%），无研究间异质性（I²=0%，P=0.76）。 结论 接受性别确认激素治疗的AMAB跨性别者总体VTE发生率为2%。在年龄<37.5岁且雌激素治疗疗程<53个月的AMAB人群中，VTE风险可忽略不计。未来仍需开展进一步研究，以明确不同类型及给药途径的雌激素治疗是否可降低37.5岁以上、接受长期激素治疗的AMAB跨性别者的VTE风险。 系统评价注册 [https://www.crd.york.ac.uk/PROSPERO/]，注册号 [CRD42021229916]。