Do reproductive women have a higher prevalence of autoimmune diseases?

From the Guidelines

Reproductive women do have a higher prevalence of autoimmune diseases compared to men, with women of reproductive age being approximately 2-10 times more likely to develop autoimmune conditions such as multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and Hashimoto's thyroiditis. This gender disparity is primarily attributed to the effects of sex hormones, particularly estrogen, which can enhance immune responses and potentially trigger autoimmune reactions in genetically susceptible individuals, as noted in a study published in the Journal of the American College of Cardiology 1. Estrogen can increase B cell survival and antibody production while affecting T cell function, creating an environment more conducive to autoimmunity. Additionally, the X chromosome contains numerous immune-related genes, and the incomplete inactivation of one X chromosome in women may contribute to immune dysregulation.

Some key points to consider in the management of reproductive health in women with autoimmune diseases include:

• The importance of effective contraception to avoid unplanned pregnancies, which can worsen disease activity and increase the risk of adverse pregnancy outcomes, as emphasized in the 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases 1.
• The need for early involvement of the rheumatologist in reproductive health discussions involving patients with rheumatic and musculoskeletal diseases, to ensure that patients receive appropriate counseling and care.
• The use of hormonal contraceptives, such as estrogen-progestin pills or progestin-only pills, which can be safe and effective for women with stable autoimmune diseases, but may require careful consideration in women with a history of thrombosis or other complications, as noted in a study published in Arthritis and Rheumatology 1.
• The importance of monitoring disease activity and adjusting treatment as needed during pregnancy, to minimize the risk of adverse outcomes and ensure the best possible outcomes for both mother and baby.

Overall, the management of reproductive health in women with autoimmune diseases requires a comprehensive and multidisciplinary approach, taking into account the complex interplay between sex hormones, immune function, and disease activity. By prioritizing early diagnosis, effective treatment, and careful monitoring, healthcare providers can help women with autoimmune diseases to achieve the best possible outcomes and improve their overall quality of life.

From the Research

Autoimmune Disease Prevalence in Reproductive Women

• Reproductive women have a higher prevalence of autoimmune disease, with women having up to a fourfold increase in risk for autoimmune disease compared to men 2.
• The mechanism for this autoimmune sex bias remains obscure, but several factors have been proposed, including sex hormones, the X chromosome, microchimerism, environmental factors, and the microbiome 2.
• Studies have shown that women have higher absolute levels of antibodies than men, and (auto)antibodies are also associated with most autoimmune diseases, which may contribute to the increased prevalence of autoimmune disease in women 2.

Factors Contributing to Autoimmune Disease in Women

• The association between increased quantities of serum antibodies and increased prevalence of autoimmunity is found not only in women, but also in men with Klinefelter syndrome 2.
• Serum antibody levels and autoimmunity spike in the postpartum period, and a dose-response effect exists between parity and both serum antibodies and prevalence of autoimmune disease 2.
• Biological plausible mechanisms, such as T cell-dependent activation of B cells and/or VGLL3, may explain the association between increased antibodies and autoimmune disease in women 2.

Specific Autoimmune Diseases Affecting Women

• Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease that predominantly affects women of childbearing age 3.
• SLE is one of the many autoimmune diseases that affect women, with 80% of characterized conditions being diagnosed in women 4.
• Other autoimmune diseases that affect women include type 1 diabetes mellitus, Hashimoto's thyroiditis, and rheumatoid arthritis 4, 5.

Research and Clinical Implications

• Research should focus on optimizing the use of current therapy and improving the quality of care of patients with autoimmune diseases, particularly women 3.
• An inclusive approach to addressing disparities for women living with autoimmune diseases is necessary, recognizing and incorporating intersectional experiences of diverse populations of women into biomedical research, clinical practice, and policy solutions 4.
• Clinical trials for autoimmune diseases, such as SLE, should be designed to improve the potential success rate of future trials, including the use of more realistic sample size calculations and the consideration of concomitant pharmacotherapy 6.