Menopause is an inflection point of age-related immune changes in women

Elevated proinflammatory cytokines in postmenopausal women is considered as one of the causes increasing the incidence of chronic inflammatory diseases. However, the details of postmenopausal immune changes have not yet been fully revealed. Thus, we investigated age-related immune changes in women and compared immune responses in postmenopausal and reproductive-age women. A total of 34 postmenopausal women and 91 reproductive-age women were included in the study. After isolating peripheral blood mononuclear cells, analysis of immunophenotypes and intracellular cytokine profiles were done. The proportion of natural killer (NK) cells was significantly higher, and the ratio of TNF-α- to IL-10-producing CD3+CD4 + T cells (Th1 to Th2) and the ratio of Th17 cells to CD4+CD25+Foxp3+ regulatory T (Treg) cells (Th17 to Treg) were higher, in postmenopausal women than in reproductive-age women. The Treg cell proportion was negatively correlated with the Th1 and Th2 cell proportions in reproductive-age women but not in postmenopausal women. As age increased, the proportion of Tregs was increased in reproductive-age women (r = 0.302, p = 0.004), whereas the proportion of Th1 cells was increased in postmenopausal women (r = 0.466, p = 0.005). FSH levels showed a positive correlation with Fopx3+ T cell and Treg cell (p = 0.04, 0.053, respectively), whereas Th17/Treg ratio and Th1 cell showed negative correlation with FSH.(p = 0.045, 0.024, respectively). In conclusion, postmenopausal women have higher proinflammatory immune statuses, as demonstrated by increased proportions of NK, Th1, and Th17 cells, altered correlations among NK and T cell subsets, and compromised balances between effector T cell subsets.