Menopausal hormone therapy and the risk of systemic lupus erythematosus and systemic sclerosis: a population-based nested case-control study

Abstract Objectives Systemic lupus erythematosus (SLE) and systemic sclerosis (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. Methods 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 National Patient and Prescribed Drug Register as well as Longitudinal Integration Database for Health Insurance and Labour Market Studies. Exposure was defined as 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% confidence intervals (CI), varied by type, route of administration, and duration of use, was assessed using conditional logistic regression, adjusted for education, income, and sick leave. Results 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 highest risk of SLE (OR = 1.9; 95% CI: 1.4–2.7) and SSc (OR = 1.8; 95% CI: 1.2–2.5). Conclusion 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.