Down-regulated progesterone receptor A and B coinciding with successful treatment of endometrial hyperplasia by the levonorgestrel impregnated intrauterine system

Abstract

Objective: To investigate whether regression of endometrial hyperplasia observed after 3 months of treatment with levonorgestrel impregnated intrauterine system device (LNG-IUS) was sustained after 6 months and whether these effects were still occurring synchronously with extinguished expression of progesterone receptors and increased apoptosis.

Design: Retrospective population-based observational study.

Setting: Six local hospitals and one university hospital in northern Norway.

Population: Patients (n = 41) with low and medium risk endometrial hyperplasia.

Methods: Histopathological treatment response comparing LNG-IUS (n = 25) and standard per oral medroxyprogesterone (n = 16). Expression of progesterone receptor A (PR-A), progesterone receptor B (PR-B), ER-alpha, ER-beta, Bcl-2, BAX, Caspase-3 and metallothionein (MT) were investigated by immunohistochemistry; results were evaluated by a semi-quantitative H-score.

Main outcome measures: Response to progestin treatment.

Results: All the LNG-IUS treated patients had therapy response after 6 months. PR-A and PR-B in glands were almost extinguished for IUD users compared to the oral group. Estrogen receptors were also reduced. Co-existent changes in apoptosis were differently modulated in glands and stroma in the two treatment groups. Bcl-2 was different in glands and stroma in responders and non-responders to oral therapy.

Conclusion: The study confirms that LNG-IUS can be safely used for 6 months as treatment for endometrial hyperplasia. The clinical effect is accompanied by almost extinguished PR-receptors in glands coinciding with modulation of apoptosis. The results strongly indicate that progestins activate non-classical initiated signaling pathways.