Spatiotemporal single-nuclei analysis of the PCOS-endometrium reveals that 16 weeks of metformin and lifestyle management reverse many dysregulated genes, particularly in epithelial SOX9+LGR5+ and AR+ cells, stromal fibroblasts, SMCs and uNK2 and uM2 subpopulations. Here, LGR5 is linked to polycystic ovary syndrome.