楊順發YANG, SHUN-FA陳劭嘉CHEN, SHAO-CHIASHAO-CHIACHEN醫學研究所碩士班2026-10-292025-07-2120252025-06-24https://handle.ncl.edu.tw/11296/whmr6rhttps://scholars.csmu.edu.tw/handle/123456789/36738研究背景：透納氏症（Turner Syndrome, TS）為女性常見的性染色體異常疾病，患者除生長遲緩與第二性徵發育不全外，亦面臨心血管、代謝、內分泌與生殖系統等多重共病風險。生長激素替代療法（Growth Hormone Replacement Therapy, GHRT）與雌激素替代療法（Estrogen Replacement Therapy, ERT）為臨床主要治療方式，然而針對其長期健康影響的實證研究仍有限，且族群與年齡異質性對治療反應的潛在影響亦尚未明確。研究方法：本研究使用美國與全球多中心電子病歷資料庫 TriNetX，納入診斷為透納氏症的患者，依是否接受 GHRT 或 ERT 分組。採傾向分數配對（Propensity Score Matching, PSM）控制潛在混雜因子，進行 Cox 比例風險回歸模型分析，以比較各組在主要共病發生風險上的差異。主分析針對美國地區資料進行，並進一步進行全球敏感性分析，及按年齡與種族分層之次分析。研究結果：在 GHRT 分析中，美國地區接受 GHRT 者，心肌病與第二型糖尿病風險顯著降低；然而甲狀腺炎、腦下垂體功能低下、卵巢功能障礙與青春期障礙風險則顯著上升。全球資料分析結果方向與主分析一致，僅有 GHRT 在第二型糖尿病的結果有所不同；而ERT 的結果則在腦下垂體功能及青春期障礙有所不同。種族分層次分析顯示，接受 GHRT 者及 ERT 的白人患者，均在心肌病風險上具有顯著保護效果，而黑人患者則是均在卵巢功能障礙的風險上升顯著。年齡分層次分析則顯示內分泌與發育相關共病風險於青春期年齡組最為顯著。在 GHRT 分析中，卵巢功能障礙、青春期障礙、甲狀腺炎與腦下垂體功能低下的風險均顯著增加；在 ERT 分析中，觀察到卵巢功能障礙與甲狀腺相關共病風險增加，且在40 歲以上族群中首次觀察到心肌病與第二型糖尿病風險下降的趨勢。討論：本研究顯示 GHRT 與 ERT可能帶來代謝與心血管保護，但也伴隨內分泌與發育軸相關風險上升。GHRT 與 ERT 的風險效益於不同年齡層與族群間存在差異，反映出臨床上應更精準考量患者特性。部分結果可能受限於資料異質性、樣本數與「健康使用者偏倚」影響。由於 TriNetX 無基因型資訊，無法探討不同染色體型態對療效的影響，未來研究可進一步整合遺傳資料與長期追蹤，以優化治療決策與照護策略。Background: Turner syndrome (TS) is a common sex chromosome disorder in females, characterized not only by short stature and insufficient secondary sexual development but also by increased risk for multiple comorbidities involving cardiovascular, metabolic, endocrine, and reproductive systems. Growth Hormone Replacement Therapy (GHRT) and Estrogen Replacement Therapy (ERT) are the cornerstone treatments for TS. However, empirical evidence regarding their long-term health impacts remains limited, and the potential influence of demographic and age-related heterogeneity on treatment response is yet to be clarified.Methods: This study utilized data from the TriNetX global and U.S. multicenter electronic health record databases to identify patients diagnosed with TS. Patients were stratified based on whether they received GHRT or ERT. Propensity score matching (PSM) was applied to control for confounding variables, and Cox proportional hazards models were used to assess differences in the risk of major comorbidities. The primary analysis focused on the U.S. cohort, followed by global sensitivity analyses and stratified subgroup analyses by age and race.Results: In the GHRT analysis, U.S. patients receiving GHRT demonstrated significantly lower risks of cardiomyopathy and type 2 diabetes mellitus, while increased risks were observed for thyroiditis, hypopituitarism, ovarian dysfunction, and pubertal disorders. Global data generally corroborated these findings, with the exception of the diabetes outcome. ERT analysis revealed similar patterns across U.S. and global datasets, with consistent reductions in the risks of cardiomyopathy and type 2 diabetes, and increased risks of ovarian dysfunction and thyroid-related comorbidities. Subgroup analyses showed that White patients benefited more from GHRT in terms of cardioprotective effects, whereas Black patients had a higher risk of ovarian and pubertal disorders. Age-stratified analyses indicated that endocrine and developmental comorbidity risks were most prominent during adolescence (11–30 years). Notably, patients aged ≥ 40 years receiving ERT exhibited significant reductions in cardiomyopathy and diabetes risk for the first time.Discussion: This study highlights the dual nature of GHRT and ERT in TS—while offering potential cardiometabolic benefits, they may concurrently increase the risk of endocrine and developmental dysfunctions. The risk-benefit profiles of GHRT and ERT appear to vary by age and race, underscoring the need for precision medicine approaches in clinical decision-making. Certain findings may be influenced by data heterogeneity, limited sample sizes, or the “healthy user bias.” Furthermore, due to the absence of genotype information in the TriNetX database, this study could not assess the differential effects of specific karyotypes. Future research integrating genetic data with long-term follow-up is warranted to refine therapeutic strategies and optimize care in this population.透納氏症生長激素替代療法雌激素替代療法大型資料庫世代研究Turner SyndromeGrowth Hormone Replacement TherapyEstrogen Replacement TherapyLarge-Scale Cohort Studythesis