Effects of the levonorgestrel-releasing intrauterine system on proliferation and apoptosis in the endometrium

BACKGROUND: The levonorgestrel-releasing intrauterine system (LNg-IUS) has been shown to be effective in the management of menorrhagia. In order to ev aluate the effects of LNg-IUS on endometrial proliferation and apoptosis, p roliferating cell nuclear antigen (PCNA) expression, apoptosis, Fas and Bcl -2 protein expression in the endometrium were determined at the early proli ferative phase of the menstrual cycle before and 3 months after LNg-IUS ins ertion. METHODS: PCNA, Fas and Bcl-2 protein expression were analysed using an avidin-biotin immunoperoxidase method. Apoptosis was assessed by the te rminal deoxynucleotidyl transferase-mediated deoxy-UTP nick-end labelling ( TUNEL) method. RESULTS: PCNA, immunolocalized both in the nuclei of endomet rial glands and stroma was less abundant 3 months after insertion (P < 0.05 ). Bcl-2 protein, immunolocalized in the cytoplasm of endometrial glands bu t not in the stroma, became scanty 3 months after insertion. Fas antigen, i mmunolocalized. only in endometrial glands before insertion, became promine nt in both endometrial glands and stroma 3 months after insertion. The apop tosis-positive rate of the nuclei in both endometrial glands and stroma was significantly higher 3 months after insertion relative to that before inse rtion (P < 0.05). CONCLUSIONS: LNg-IUS resulted in a decrease in endometria l proliferation and an increase in apoptosis in endometrial glands and stro ma. The increase in apoptosis associated with increased Fas antigen express ion and decreased Bcl-2 protein expression in the endometrium may be one of the underlying molecular mechanisms by which LNg-IUS insertion causes the atrophic change of the endometrium.