Reproductive Endocrinology · Apr 18, 2026

Menopause, immunity, and autoimmune rheumatic diseases – pathogenetic intersections and clinical implications

By Yehudіna Y, Trypilka S

Menopause is a physiological stage in a woman’s life characterized by permanent ovarian failure and sustained estrogen deficiency, leading to systemic endocrine, metabolic, and immunological changes. Declining estrogen levels are associated with the development of a pro-inflammatory immune phenotype, immunosenescence, and disruption of the delicate balance between innate and adaptive immunity. These mechanisms are highly relevant to autoimmune and rheumatic diseases, as menopause may modify disease expression, clinical manifestations, and long-term complications rather than acting solely as a chronological event. Estrogens play a central role in regulating macrophage function, T- and B-cell responses, cytokine production, and immune tolerance. Estrogen deficiency promotes a shift toward Th1- and Th17-driven immune responses, reduction of regulatory T cells, and enhanced activity of pro-inflammatory mediators. In parallel, age-related immune remodeling, including epigenetic alterations, may further amplify chronic inflammation and contribute to cumulative organ damage. In patients with rheumatoid arthritis and systemic scleroderma, menopause is more often associated with poorer functional outcomes and an increased risk of vascular complications, whereas postmenopausal lupus erythematosus usually has a milder clinical course. Sjögren’s disease has a peak incidence in the perimenopause, indicating a significant role for estrogen deficiency in exocrine gland damage. Menopause also has a profound impact on the musculoskeletal system, accelerating bone loss and increasing the risk of osteoporosis and fragility fractures, particularly in women with chronic inflammatory conditions. These effects result from the combined influence of estrogen deficiency, immune dysregulation, and persistent low-grade inflammation. Menopausal hormone therapy may be considered in patients with rheumatic diseases to alleviate symptoms related to estrogen deficiency within an individualized risk–benefit framework. In particular, menopausal hormone therapy helps reduce musculoskeletal pain, improve a woman’s well-being and quality of life, alleviate urogenital symptoms in patients with Sjögren’s disease, and reduces the frequency of exacerbations and the risk of developing ACPA-positive rheumatoid arthritis.

doi.org/10.18370/2309-4117.2026.82.74-82Open accessMechanisms