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


Baytur Y. B., Ozbilgin K., Cilaker S., Lacin S., Kurtul O., Oruc S., ...More

EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY, vol.135, no.1, pp.94-103, 2007 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 135 Issue: 1
  • Publication Date: 2007
  • Doi Number: 10.1016/j.ejogrb.2006.07.042
  • Journal Name: EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.94-103
  • Keywords: raloxifene, gosereline, leiomyoma, estrogen receptor, progesterone receptor, bcl-2 and p53, GONADOTROPIN-RELEASING-HORMONE, RANDOMIZED CLINICAL-TRIAL, MENSTRUAL-CYCLE, POSTMENOPAUSAL WOMEN, OVARIECTOMIZED RATS, GENE-EXPRESSION, BREAST-CANCER, UP-REGULATION, AGONIST, MYOMETRIUM
  • Dokuz Eylül University Affiliated: Yes

Abstract

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. Study design: 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). Conclusion: 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. (c) 2006 Elsevier Ireland Ltd. All rights reserved.