Uncovering immune signatures of the endometrium in heavy menstrual bleeding: a cross-sectional study

Dysregulation of leukocyte cell number as a cause of heavy menstrual bleeding (HMB) has not been investigated much. The present study compares the changes in the number of uterine natural killer (uNK) cells, T cells, and macrophages in endometrial samples from women with normal menstrual cycles versus those with HMB.

We analyzed endometrial tissue from 98 patients (73 with HMB; 25 with normal cycles) using immunohistochemistry to semi-quantitatively estimate the degree of cluster of differentiation (CD)56+, CD8+, CD4+, and CD68+ cell infiltration.

No statistically significant differences were observed in the CD4+, CD8+, CD56+, or CD68+ cell counts between women with HMB and controls during either the proliferative or secretory phases of the menstrual cycle. CD56+ natural killer cells were relatively reduced in the HMB group during the proliferative phase, with higher counts in the control group (P=0.071). CD68+ macrophages/high-power field (hpf) showed a strong positive correlation with CD4+ T cells (r, 0.481; P<0.001), CD8+ T cells (r, 0.641; P<0.001), and CD56+ uNK cells (r, 0.404; P<0.001). CD8+ cells/hpf demonstrated a significant positive correlation with uterine volume, CD4+ cells/hpf, CD68+ cells/hpf, and CD56+ cells/hpf.

Although no single immune cell type was independently associated with HMB compared with controls, the observed significant correlations among CD4+, CD8+, CD56+, and CD68+ highlight the interconnected nature of endometrial immune activity.