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


METHODS
Retrospective population-based observational study.


METHODS
Six local hospitals and one university hospital in northern Norway.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Orbo
Anne
A
Institute of Medical Biology, University of Tromsø, Norway. anne.orbo@uit.no
Arnes
Marit
M
Pettersen
Inger
I
Larsen
Kurt
K
Hanssen
Karin
K
Moe
Bjorn
B
D000328:Adult; D053143:Caspase 2 / Q000378:metabolism; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage*; D015536:Down-Regulation; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007436:Intrauterine Devices, Medicated; D016912:Levonorgestrel / Q000008:administration & dosage*; D008668:Metallothionein / Q000378:metabolism; D008875:Middle Aged; D009664:Norway; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D003280:Contraceptives, Oral, Synthetic; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019253:Proto-Oncogene Proteins c-bcl-2; D011980:Receptors, Progesterone; D051028:bcl-2-Associated X Protein; C101118:progesterone receptor A; C097314:progesterone receptor B; D016912:Levonorgestrel; D008668:Metallothionein; D053143:Caspase 2