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

• Published in: Acta Obstetricia et Gynecologica Scandinavica
• Main Authors: Ørbo, Anne, Arnes, Marit, Pettersen, Inger, Larsen, Kurt, Hanssen, Karin, Moe, Bjorn
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2010
• Subjects: Obstetrics and Gynecology; General Medicine; Norway; Northern Norway
• Online Access: http://dx.doi.org/10.3109/00016349.2010.512068; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.3109%2F00016349.2010.512068; https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.3109/00016349.2010.512068

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.