A comparative study of the effect of raloxifene and gosereline on uterine leiomyoma volume changes and estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically in premenopausal women.
OBJECTIVE
To compare the mechanism of action of raloxifene and gosereline induced shrinkage of leiomyomas via estrogen receptor, progesterone receptor, bcl-2 and p53 expression immunohistochemically.


METHODS
Thirty-two premenopausal women affected by uterine leiomyomas were randomized into two equal groups. Group A was treated with gosereline (3.6 mg subcutaneous injection monthly) and group B was treated with raloxifene (60 mg daily per os) for 3 months before undergoing surgery. At entry and at the end of the treatment the leiomyoma volume was measured ultrasonografically and the volume change was calculated. Immunohistochemical detection of estrogen receptor (ER), progesterone receptor (PR), bcl-2 and p53 were performed on leiomyoma tissue samples from group A, group B and the matched-control group. H-scores for ER, PR, bcl-2 and p53 were calculated. The mean volume changes of leiomyomas and immunohistochemical H-score differences of ER, PR, bcl-2 and p53 were compared between groups.


RESULTS
The leiomyoma volume decreased significantly after treatment in gosereline group from baseline of 65 cm(3) to 35 cm(3), and in raloxifene group from 68 cm(3) to 50 cm(3), p<0.05. The difference between the before and after treatment leiomyoma volumes between the two treatments was not statistically significant. H-score of ER expression was significantly lower in gosereline group compared to control group (54.4 versus 113.2, p = 0.001), whereas H-score of PR expression was significantly lower with both gosereline and raloxifene groups compared to control group (64.8 for gosereline versus 94.6 for control, 73.6 for raloxifene versus 94.6 for control, p = 0.001). The bcl-2 expression was higher in both gosereline and raloxifene groups compared to control group (173.7 for gosereline versus 94.7 for control, 179.7 for raloxifene versus 94.7 for control, p = 0.001). The p53 expression was only lower with gosereline than the control group (169.4 versus 205.6, p = 0.001), whereas there was no significant change between the raloxifene group and the control group (201.9 versus 205.6) (p>0.05).


CONCLUSIONS
Raloxifene was as effective as gosereline in reducing leiomyoma volumes. Decreased PR expression may be a mechanism for tumor growth reduction in raloxifene treatment. In both treatment modalities, the mechanism of shrinkage of leiomyomas could not be increased apoptosis mediated by bcl-2 and p53 expression and should be investigated by further studies.
Baytur
Yesim Bulbul
YB
Celal Bayar University School of Medicine, Department of Obstetrics and Gynecology, Turkey. yesim_bulbul@yahoo.com
Ozbilgin
Kemal
K
Cilaker
Serap
S
Lacin
Selman
S
Kurtul
Ozgur
O
Oruc
Semra
S
Koyuncu
Faik Mumtaz
FM
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D005260:Female; D019254:Genes, bcl-2 / Q000187:drug effects; D017273:Goserelin / Q000494:pharmacology*; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators; D016159:Tumor Suppressor Protein p53; D017273:Goserelin; D020849:Raloxifene Hydrochloride