Sex bias in autoimmunity: a life-course perspective and practical guidance for the field

Sex differences in autoimmunity are among the most striking in human disease, yet they are often presented as fixed biological constants. A life course perspective reveals that sex bias emerges, intensifies or attenuates across developmental stages, shaped by interactions between sex chromosomes, hormonal transitions, immune maturation, environmental exposures and structural biases in research and clinical practice. We aimed to synthesise current evidence on sex bias in autoimmunity across the life course and to provide practical guidance for improving terminology, study design, reporting and interpretation in sex-aware autoimmune research. This narrative review integrates findings from immunology, endocrinology, epidemiology and methodological literature. Particular emphasis was placed on developmental transitions, including prepubertal, pubertal, reproductive, postpartum, menopausal and ageing stages and on identifying modifiable sources of bias in research practice.

Sex differences in autoimmunity vary substantially across the lifespan. Early life immune programming, puberty-related hormonal shifts, reproductive transitions, pregnancy and postpartum immune modulation and menopause all contribute to dynamic patterns of disease susceptibility and expression. Structural factors, including diagnostic bias, sampling bias and insufficient sex stratified analyses, frequently distort interpretation of biological differences. Current research practices often conflate sex and gender, underpower sex-specific analyses and fail to report sex-disaggregated outcomes, limiting scientific rigour and clinical applicability.

Sex bias in autoimmunity is not static but evolves with developmental and hormonal transitions. Addressing this complexity requires deliberate changes in research practice. Embedding a life course framework is essential for improving the accuracy, relevance and translational value of autoimmune research.