Menopausal Hormone Therapy Increase Risk of Autoimmune Diseases: Study

A new Swedish study published in the Rheumatology journal suggests that menopausal hormone therapy (MHT) may increase the risk of developing autoimmune conditions, including systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). 

This nested case-control study investigated the association between MHT and these autoimmune diseases. The study analyzed data collected from Sweden’s National Patient and Prescribed Drug Register, covering women diagnosed with SLE and SSc between 2009 and 2019. A total of 943 women with SLE and 733 women with SSc were identified, along with matched controls from the general population.

This study examined the medical histories of the participants by focusing on MHT use before diagnosis. The analysis considered factors such as education level, income, and sick leave. The findings of this study revealed a marked link between MHT use and a higher risk of developing SLE and SSc. Women who used MHT had a 30% increased risk of developing SLE (odds ratio [OR] = 1.3; 95% confidence interval [CI]: 1.1–1.6) and a 40% increased risk of developing SSc (OR = 1.4; 95% CI: 1.2–1.7) when compared to women who did not use MHT.

Moreover, the risk varied based on the type and route of MHT administration. Women who used a combination of systemic and local MHT medications were at the highest risk, with a nearly 2-fold increase in SLE risk (OR = 1.9; 95% CI: 1.4–2.7) and an 80% increased risk of SSc (OR = 1.8; 95% CI: 1.2–2.5). The research highlighted that the association between MHT and these autoimmune conditions was independent of socioeconomic factors, by suggesting that the use of exogenous female sex hormones might play a role in triggering or exacerbating these diseases.

Autoimmune diseases like SLE and SSc disproportionately affect women, and hormonal differences have long been suspected to contribute to this gender disparity. The findings of this study underline the need for further investigation into how MHT might influence the pathogenesis of these conditions. Women considering or currently using MHT may want to discuss these risks with their clinicians, particularly if they have a family history of autoimmune diseases.

Overall, these findings emphasized the need for further research to explore the underlying mechanisms and confirm causation. The findings are a critical step toward understanding the complex relationship between hormone therapy and autoimmune diseases in women.

Source:

Patasova, K., Dehara, M., Mantel, Ä., Bixo, M., Arkema, E. V., & Holmqvist, M. (2025). Menopausal hormone therapy and the risk of systemic lupus erythematosus and systemic sclerosis: a population-based nested case-control study. Rheumatology (Oxford, England). https://doi.org/10.1093/rheumatology/keaf004