Safety of Hormonal Replacement Therapy and Oral Contraceptives in Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis

BackgroundThere is conflicting data regarding exogenous sex hormones [oral contraceptives (OC) and hormonal replacement therapy (HRT)] exposure and different outcomes on Systemic Lupus Erythematosus (SLE). The aim of this work is to determine, through a systematic review and meta-analysis the risks associated with estrogen use for women with SLE as well as the association of estrogen with developing SLE.Methods and FindingsMEDLINE, EMBASE, SciElo, BIREME and the Cochrane library (1982 to July 2012), were databases from which were selected and reviewed (PRISMA guidelines) randomized controlled trials, cross-sectional, case-control and prospective or retrospective nonrandomized, comparative studies without language restrictions. Those were evaluated by two investigators who extracted information on study characteristics, outcomes of interest, risk of bias and summarized strength of evidence. A total of 6,879 articles were identified; 20 full-text articles were included. Thirty-two meta-analyses were developed. A significant association between HRT exposure (Random model) and an increased risk of developing SLE was found (Rate Ratio: 1.96; 95%-CI: 1.51–2.56; P-valueConclusionAn association between HRT exposure and SLE causality was observed. No association was found when analyzing the risk for SLE among OC users, however since women with high disease activity/Thromboses or antiphospholipid-antibodies were excluded from most of the studies, caution should be exercised in interpreting the present results. To identify risk factors that predispose healthy individuals to the development of SLE who are planning to start HRT or OC is suggested.

背景：目前关于外源性性激素[口服避孕药（oral contraceptives, OC）与激素替代疗法（hormonal replacement therapy, HRT）]暴露与系统性红斑狼疮（Systemic Lupus Erythematosus, SLE）不同预后的相关数据存在争议。本研究旨在通过系统评价与meta分析，明确系统性红斑狼疮患者使用雌激素的相关风险，以及雌激素暴露与系统性红斑狼疮发病的关联。
方法与结果：本研究检索了MEDLINE、EMBASE、SciElo、BIREME及Cochrane图书馆（1982年至2012年7月）的文献，依据PRISMA指南筛选并纳入无语言限制的随机对照试验、横断面研究、病例对照研究，以及前瞻性或回顾性非随机对照比较研究。由两名研究者独立对纳入文献进行评价，提取研究特征、目标结局、偏倚风险及证据总结强度相关信息。本研究共检索到6879篇文献，最终纳入20篇全文文献，共完成32项meta分析。研究发现，激素替代疗法暴露（随机效应模型）与系统性红斑狼疮发病风险升高存在显著关联（率比：1.96；95%置信区间：1.51–2.56；P值未明确给出）。
结论：本研究观察到激素替代疗法暴露与系统性红斑狼疮发病存在因果关联。在分析口服避孕药使用者的系统性红斑狼疮发病风险时未发现显著关联，但由于多数研究均排除了疾病活动度较高、合并血栓形成或抗磷脂抗体阳性的女性群体，因此解读本研究结果时应保持谨慎。建议进一步识别存在系统性红斑狼疮发病易感倾向的健康个体的风险因素，为计划启动激素替代疗法或口服避孕药使用的人群提供临床指导。