Dynamic Shifts in Lymphocyte Subsets During the Menopausal Transition and Sexual Dimorphism in Immunosenescence

Immunosenescence demonstrates marked sexual dimorphism, yet the dynamic changes in lymphocyte subsets across the female menopausal transition are poorly defined. This study characterized these age- and sex-related immune variations in a large Chinese cohort.

In this cross-sectional study, we analyzed 4209 healthy adults using flow cytometry to quantify lymphocyte subsets and PD-1 expression. Females were stratified by age and reproductive stage. Sex comparisons were performed after propensity score age-matching.

Analysis of the female cohort revealed dynamic immune shifts during the menopausal transition, characterized by a "scissor-like" pattern: CD3⁺CD4⁺ T cells (%) and the CD4/CD8 ratio peaked at 55-59 years, while CD3⁺CD8⁺ T cells (%) declined continuously (all p < 0.001). Notably, CD19⁺ B cells (%) increased with age in females but decreased in males. After age-matching, pronounced sexual dimorphism was confirmed: females exhibited significantly higher levels of CD3⁺ T cells, CD3⁺CD4⁺ T cells, CD19⁺ B cells, NK cells, and CD4/CD8 ratio, alongside lower PD-1 expression on CD4⁺ T cells and NK cells (all p < 0.001). In contrast, PD-1 expression on CD8⁺ T cells was higher in females (p < 0.001).

These findings suggest that the perimenopausal period represents a key phase of immune remodeling in women, and support the integration of sex and reproductive stage into future immunosenescence research and clinical strategies.