2025/01/01 by Toitou, Melpomeni, Iacovantuono, Maria, Sauer, Gesa +5
Medicine · #610 Medicine & #Inflammatory Myopathies and Dermatomyositis #Multiple Sclerosis Research Studies #Systemic Sclerosis and Related Diseases #epidemiology #gender #health #pathogenesis #prognosis #sex #sex differences #systemic sclerosis #treatment response
paper · doi:10.5167/uzh-280988
openalex publication_date 2025/01/01 · openalex created_date 2025/12/11 · openalex updated_date 2026/07/28
Systemic sclerosis (SSc) exhibits sex-related disparities in prevalence, clinical features, and outcomes. While women are more frequently affected, men often experience a more severe disease course, including diffuse cutaneous involvement, interstitial lung disease, and reduced survival. These differences are shaped by biological factors such as sex hormones and genetic influences. Estrogens and androgens differentially influence immune and fibrotic pathways, while life stages such as menopause further modulate disease expression. Genetic mechanisms, including X chromosome inactivation, regulation of immune-related genes, and cell signaling pathways, vary between sexes and also play an important role in the sex bias seen in SSc. In addition to these biological aspects, gender, as a sociocultural factor involving roles, behaviors, and access to care, may further modify disease perception, healthcare engagement, and outcomes, though it remains underexplored in SSc research. Treatment responses may also vary by sex, as suggested by emerging studies, but sex-specific clinical recommendations are still lacking. This review aims to summarize current knowledge on sex-related differences in SSc and highlight implications for clinical management and future research. Understanding how sex influences Systemic Sclerosis: From underlying causes to symptoms and treatment Systemic sclerosis (SSc) is a complex autoimmune disease that affects the skin and internal organs. It is more common in women than in men, but men often experience a more severe disease course. This includes greater organ involvement and poorer overall outcomes. Biological factors, such as sex hormones and genetic differences, are thought to play a central role in these disparities. Estrogens and androgens affect immune responses and the development of fibrosis in different ways. Changes in hormone levels across life stages, such as during menopause, can also influence how the disease appears. Genetic mechanisms, including how genes on the X chromosome are expressed, contribute further to the differences seen between men and women. In addition to these biological influences, gender-related factors, such as differences in social roles, health behaviors, and access to care, may also affect how people experience the disease and respond to treatment. However, these aspects are still poorly studied in SSc. This review outlines the current understanding of how sex shapes the development, clinical presentation, and treatment responses in SSc, and emphasizes the need for more personalized approaches in both research and clinical care.