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

Abstract

Objectives: 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.

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 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.

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 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).

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.

Keywords: SSc; lupus; menopausal hormone therapy.

Figure 1.

Associations with menopausal hormone therapy according to time between the first dispensation and the index date. Forest plot of odds ratios and their respective 95% CI distributions according to time since first menopausal hormone therapy dispensation. The vertical dashed line denotes odds ratio of 1.0. Conditional logistic models were adjusted for years of education and gross yearly income during the calendar year before index date, sick leave (yes vs no) during 2005

Figure 2.

Associations between menopausal hormone therapy and SLE and SSc according to the age at first dispensation of menopausal hormone therapy. MHT, menopausal hormone therapy. Forest plot of odds ratios and their respective 95% CI distributions according to age at first dispensation of menopausal hormone therapy dispensation. The vertical dashed line denotes odds ratio of 1.0. Conditional logistic models were adjusted for years of education and gross yearly income during the calendar year before index date, sick leave (yes vs no) during 2005