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Abstract

Effects of the levonorgestrel-releasing intrauterine system on proliferation and apoptosis in the endometrium 
Maruo,Takeshi; Laoag-Fernandez,Jovelle B.; Pakarinen,Paivi; Murakoshi,H.; Spitz,Irving M.; Johansson,Elof D.B.
Human Reproduction 16(10): 2103-2108
Publication date: 2001

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Background
The levonorgestrel-releasing intrauterine system(LNg-IUS) has been shown to be effective in the management ofmenorrhagia. In order to evaluate the effects of LNg-IUS onendometrial proliferation and apoptosis, proliferating cellnuclear antigen (PCNA) expression, apoptosis, Fas and Bcl-2protein expression in the endometrium were determined at theearly proliferative phase of the menstrual cycle before and3 months after LNg-IUS insertion.

Methods
PCNA, Fas and Bcl-2protein expression were analysed using an avidin-biotinimmunoperoxidase method. Apoptosis was assessed by the terminaldeoxynucleotidyl transferase-mediated deoxy-UTP nick-end labelling(TUNEL) method.

Results
PCNA, immunolocalized both in the nucleiof endometrial glands and stroma was less abundant 3 monthsafter insertion (P < 0.05). Bcl-2 protein, immunolocalizedin the cytoplasm of endometrial glands but not in the stroma,became scanty 3 months after insertion. Fas antigen, immunolocalizedonly in endometrial glands before insertion, became prominentin both endometrial glands and stroma 3 months after insertion.The apoptosis-positive rate of the nuclei in both endometrialglands and stroma was significantly higher 3 months after insertionrelative to that before insertion (P < 0.05).

Conclusions
LNg-IUS resulted in a decrease in endometrial proliferationand an increase in apoptosis in endometrial glands and stroma.The increase in apoptosis associated with increased Fas antigenexpression and decreased Bcl-2 protein expression in the endometriummay be one of the underlying molecular mechanisms by which LNg-IUSinsertion causes the atrophic change of the endometrium.

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