Patasova Karina, Dehara Marina, Mantel Ängla, Bixo Marie, Arkema Elizabeth V, Holmqvist Marie
Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital T2, Stockholm, Sweden.
Department of Women's Health, Division of Obstetrics, Karolinska University Hospital, Stockholm, Sweden.
Rheumatology (Oxford). 2025 Jun 1;64(6):3563-3570. doi: 10.1093/rheumatology/keaf004.
SLE and SSc are more common in women, partly due to differences in female sex hormones. Menopausal hormone therapy (MHT) is widely used to alleviate climacteric symptoms. Here, the relationship between MHT and SLE/SSc was investigated in a nested case-control study.
Women with SLE or SSc and controls, matched 1 up to 10 on sex, birth year and region, from the general population of Sweden. Data on exposures and potential confounders were obtained from the National Patient and Prescribed Drug Register as well as the Longitudinal Integration Database for Health Insurance and Labour Market Studies. Exposure was defined as the dispensation of any MHT medication prior to the diagnosis/matching. The association between MHT and SLE/SSc, and whether the strength of the association, expressed as odds ratios (OR) and 95% CI, varied by type, route of administration, and duration of use, was assessed using conditional logistic regression, adjusted for education, income and sick leave.
In total, 943 women with SLE and 733 women with SSc were identified between 2009 and 2019. We detected a significant association between MHT use and risk of SLE (OR = 1.3; 95% CI: 1.1-1.6), and SSc (OR = 1.4; 95% CI: 1.2-1.7). Women who had both systemic and local MHT medications dispensed exhibited the highest risk of SLE (OR = 1.9; 95% CI: 1.4-2.7) and SSc (OR = 1.8; 95% CI: 1.2-2.5).
These findings indicate an association between MHT and SLE/SSc, independent of socioeconomic factors, warranting further investigation into the role of exogenous female sex hormones in SLE/SSc pathogenesis.
系统性红斑狼疮（SLE）和系统性硬化症（SSc）在女性中更为常见，部分原因是女性性激素存在差异。绝经激素治疗（MHT）被广泛用于缓解更年期症状。在此，我们在一项巢式病例对照研究中调查了MHT与SLE/SSc之间的关系。
从瑞典普通人群中选取患有SLE或SSc的女性以及对照，根据性别、出生年份和地区进行1至10的匹配。暴露情况和潜在混杂因素的数据来自国家患者和处方药登记册以及健康保险和劳动力市场研究纵向整合数据库。暴露定义为在诊断/匹配之前使用任何MHT药物。使用条件逻辑回归评估MHT与SLE/SSc之间的关联，以及关联强度（以比值比（OR）和95%置信区间表示）是否因类型、给药途径和使用持续时间而有所不同，并对教育程度、收入和病假进行了调整。
在2009年至2019年期间，共识别出943例SLE女性患者和733例SSc女性患者。我们检测到使用MHT与SLE风险（OR = 1.3；95%置信区间：1.1 - 1.6）以及SSc风险（OR = 1.4；95%置信区间：1.2 - 1.7）之间存在显著关联。同时使用全身和局部MHT药物的女性患SLE（OR = 1.9；95%置信区间：1.4 - 2.7）和SSc（OR = 1.8；95%置信区间：1.2 - 2.5）的风险最高。
这些发现表明MHT与SLE/SSc之间存在关联，且独立于社会经济因素，这值得进一步研究外源性女性性激素在SLE/SSc发病机制中的作用。
