甲状腺自身免疫/甲状腺球蛋白抗体与卵巢储备功能减退之间的双向关联：观察性研究的系统综述与荟萃分析。
完整摘要 · 中文译文
背景：有证据提示甲状腺自身免疫（TAI）可能与卵巢功能障碍相关；然而，大多数研究主要关注甲状腺过氧化物酶抗体（TPOAb），而关于甲状腺球蛋白抗体（TgAb）的证据仍然有限且不一致。本研究旨在评估TAI/TgAb与卵巢储备之间的关联。 方法：在PubMed、Embase、Web of Science、CNKI数据库中对2014年1月至2025年1月发表的英文和中文文献进行了系统性文献检索。采用双向验证设计：（1）正向分析，使用标准化均数差（SMD）量化TAI阳性女性与健康对照之间血清抗苗勒管激素（AMH）水平的组间差异；（2）反向分析，量化卵巢储备功能减退（DOR）女性与健康对照之间TgAb水平差异（连续变量的SMD）和TgAb阳性率差异（二分类变量的比值比OR）。本研究前瞻性注册于PROSPERO（CRD420251207428），并按照PRISMA 2020指南开展。反向分析指反向的横断面比较，即分组变量与结局变量互换；其不意味着时间或因果关系的反转。 结果：共纳入13项研究（总n = 4,286）。正向分析（4项研究，n = 870）显示，与对照相比，TAI阳性女性的血清AMH水平显著降低（SMD=-0.20，95% CI [-0.34, -0.06]，P = 0.005，I2 = 0%）。对连续变量的反向分析（5项研究，n = 1,496）显示，与对照组相比，卵巢储备功能减退（DOR）女性的甲状腺球蛋白抗体（TgAb）水平显著升高（SMD=0.93，95% CI [0.36, 1.50]，P = 0.001，I2 = 94%）；然而，鉴于存在显著异质性，该估计值应谨慎解读。对二分类变量的反向分析（7项研究，n = 2,568）证实，与对照组相比，DOR女性TgAb阳性的几率显著更高（OR=1.65，95% CI [1.29, 2.11]，P < 0.0001，I2 = 32%）。 结论：卵巢储备功能减退与TgAb/自身免疫性甲状腺炎（TAI）阳性之间存在显著的双向关联。TAI可能损害卵巢储备，而卵巢功能不全女性的甲状腺球蛋白自身抗体负担更高。这些发现凸显了在育龄女性卵巢功能评估中进行TgAb筛查的临床重要性。 系统综述注册：https://www.crd.york.ac.uk/PROSPERO/view/CRD420251207428，注册号CRD420251207428。
完整摘要 · 英文原文
BACKGROUND: Evidence suggests that thyroid autoimmunity (TAI) may be associated with ovarian dysfunction; however, most studies have focused primarily on thyroid peroxidase antibodies (TPOAb), while evidence regarding thyroglobulin antibodies (TgAb) remains limited and inconsistent. This study aimed to evaluate the association between TAI/TgAb and ovarian reserve. METHODS: A systematic literature search was conducted in PubMed, Embase, Web of Science, CNKI databases for Chinese- and English-language articles published from January 2014 to January 2025. A bidirectional validation design was employed: (1) forward analysis, quantifying between-group differences in serum anti-Müllerian hormone (AMH) levels between TAI-positive women and healthy controls using standardized mean differences (SMD); and (2) reverse analysis, quantifying differences in TgAb levels (SMD for continuous variables) and TgAb positivity rates (odds ratios OR for dichotomous variables) between women with diminished ovarian reserve (DOR) and healthy controls. This study was prospectively registered with PROSPERO (CRD420251207428) and conducted in accordance with the PRISMA 2020 guidelines. The reverse analysis denotes a reverse-direction cross-sectional comparison in which the grouping and outcome variables are exchanged; it does not imply temporal or causal reversal. RESULTS: Thirteen studies (total n = 4,286) were included. Forward analysis (4 studies, n = 870) demonstrated significantly lower serum AMH levels in TAI-positive women compared with controls (SMD=-0.20, 95% CI [-0.34, -0.06], P = 0.005, I2 = 0%). Reverse analysis of continuous variables (5 studies, n = 1,496) revealed significantly elevated TgAb levels in women with DOR compared with controls (SMD=0.93, 95% CI [0.36, 1.50], P = 0.001, I2 = 94%); however, this estimate should be interpreted with caution given the substantial heterogeneity. Reverse analysis of dichotomous variables (7 studies, n = 2,568) confirmed that women with DOR had significantly higher odds of TgAb positivity compared with controls (OR=1.65, 95% CI [1.29, 2.11], P < 0.0001, I2 = 32%). CONCLUSIONS: A significant bidirectional association exists between diminished ovarian reserve and TgAb/TAI positivity. TAI may impair ovarian reserve, while women with ovarian insufficiency exhibit a higher burden of thyroglobulin autoantibodies. These findings highlight the clinical importance of TgAb screening in the evaluation of ovarian function among reproductive-age women. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251207428, identifier CRD420251207428.