Effect of levonorgestrel IUD and oral medroxyprogesterone acetate on glandular and stromal progesterone receptors (PRA and PRB), and estrogen receptors (ER-alpha and ER-beta) in human endometrial hyperplasia.
OBJECTIVE
The effect on progesterone and estrogen receptor expression in glands and stroma after two different treatment regimens of endometrial hyperplasia was determined.


METHODS
Pre- and post-treatment paraffin-embedded endometrial hyperplasia specimens from women treated with levonorgestrel (LNG) intrauterine device (n = 21) and women treated with 10 mg medroxyprogesterone acetate (MPA) for 10 days per cycle (n = 29) were examined immunohistochemically and evaluated by H-score (a semi-quantitative microscopical method evaluating staining intensity and number of stained cells, scale 0-3) for changes in expression of PRA (progesterone receptor A), PRB (progesterone receptor B), ER-alpha (estrogen receptor-alpha), ER-beta (estrogen receptor-beta) and AR (androgen receptors) after 3 months of treatment.


RESULTS
All the patients in the LNG IUD group responded to treatment with no sign of hyperplasia after 3 months, while only about half of the patients given MPA orally responded. Expression of PRA, PRB, ER-alpha and ER-beta were markedly reduced after progestin treatment in both treatment groups but the reduction was much more pronounced in the LNG group (H-score for PRA was reduced from 2.61 to 0.11 in glands and from 2.26 to 0.09 in stroma in LNG group. Corresponding reduction for PRB in the LNG group was from 1.96 to 0.11 and from 0.83 to 0.01. PRA was reduced from 2.53 to 1.78 in glands and from 1.93 to 1.30 in stroma in the MPA group. Corresponding reduction for PRB in the MPA group was from 2.02 to 1.25 in glands and from 0.80 to 0.34 in stroma). Weak and focal stromal expression of AR was demonstrated in 22% of the specimens before but not after therapy. There was a statistically significant reduction in both PR and ER among the responders whereas non-responders showed no statistical change after treatment.


CONCLUSIONS
The present study shows that LNG IUD causes an almost complete down-regulation (lack of immunohistochemical expression) of PR expression and a considerable down-regulation of ER expression in both glands and stroma. The changes in receptor expression were markedly less pronounced after treatment with intermittent oral MPA. The differences in receptor expression among responders and non-responders might serve as possible markers for therapy response.
Vereide
Anne Beate
AB
Department of Gynecology and Obstetrics, Institute of Clinical Medicine, Norway.
Kaino
Turid
T
Sager
Georg
G
Arnes
Marit
M
Ørbo
Anne
A
D000328:Adult; D004714:Endometrial Hyperplasia / Q000188:drug therapy* / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D047629:Estrogen Receptor beta / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007436:Intrauterine Devices, Medicated; D016912:Levonorgestrel / Q000008:administration & dosage*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D008875:Middle Aged; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D016912:Levonorgestrel; D017258:Medroxyprogesterone Acetate