Tskhakaia Irakli, Gonzalez Moret Yurilu, Palmer Anna-Kay, Lema Diego, Musri M Carolina, Tsibadze Nanuka, Lau Arthur
Jefferson Einstein Hospital, Philadelphia, Pennsylvania.
Johns Hopkins Bayview Medical Center and Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland.
ACR Open Rheumatol. 2025 Jan;7(1):e11774. doi: 10.1002/acr2.11774. Epub 2024 Dec 10.
The aim of this study was to investigate the impact of estrogen and progesterone analog supplementation on the development of autoimmune conditions.
This retrospective observational study used data from the TriNetX network, which comprised over 100 million patients from 89 health care organizations. We compared patients exposed to estrogen and progesterone analogs to those exposed to progesterone-only therapy, using 1:1 propensity score matching based on age, ethnicity, and additional criteria. The primary outcomes were incidences of various autoimmune conditions.
We included 3,338,925 patients in the group who received estrogen and progesterone and 2,090,758 patients in the group who received progesterone only. Prematching, the group who received combined therapy showed increased risks for Sjögren disease (risk ratio [RR] 1.46), rheumatoid arthritis (RR 1.1), and other autoimmune conditions. Postmatching, significant associations persisted for most conditions, with increased risks for systemic sclerosis, systemic lupus erythematosus, giant cell arteritis, Behcet disease, psoriatic arthritis, reactive arthritis, and ankylosing spondylitis. The group who received combination therapy appeared to have lower risks of developing antiphospholipid syndrome (RR 0.7).
Combined estrogen and progesterone therapy is associated with an increased risk of several autoimmune conditions. The role of estrogen, despite its protective effects against some conditions, underscores the complex interplay of sex hormones in autoimmunity. Further prospective studies are needed to elucidate underlying mechanisms and evaluate causality.
本研究旨在探讨补充雌激素和孕激素类似物对自身免疫性疾病发展的影响。
这项回顾性观察性研究使用了TriNetX网络的数据，该网络包含来自89个医疗机构的超过1亿患者。我们使用基于年龄、种族和其他标准的1:1倾向评分匹配，将暴露于雌激素和孕激素类似物的患者与仅接受孕激素治疗的患者进行比较。主要结局是各种自身免疫性疾病的发病率。
我们纳入了3338925例接受雌激素和孕激素治疗的患者以及2090758例仅接受孕激素治疗的患者。在匹配前，接受联合治疗的组患干燥综合征（风险比[RR] 1.46）、类风湿性关节炎（RR 1.1）和其他自身免疫性疾病的风险增加。匹配后，大多数疾病仍存在显著关联，系统性硬化症、系统性红斑狼疮、巨细胞动脉炎、白塞病、银屑病关节炎、反应性关节炎和强直性脊柱炎的风险增加。接受联合治疗的组患抗磷脂综合征的风险似乎较低（RR 0.7）。
雌激素和孕激素联合治疗与几种自身免疫性疾病的风险增加有关。雌激素尽管对某些疾病有保护作用，但其作用凸显了性激素在自身免疫中的复杂相互作用。需要进一步的前瞻性研究来阐明潜在机制并评估因果关系。
