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1.
Eur J Obstet Gynecol Reprod Biol ; 135(1): 94-103, 2007 Nov.
Article in English | MEDLINE | ID: mdl-16973256

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.


Subject(s)
Antineoplastic Agents, Hormonal/pharmacology , Goserelin/pharmacology , Leiomyoma/drug therapy , Raloxifene Hydrochloride/pharmacology , Selective Estrogen Receptor Modulators/pharmacology , Uterine Neoplasms/drug therapy , Adult , Female , Genes, bcl-2/drug effects , Humans , Leiomyoma/metabolism , Middle Aged , Proto-Oncogene Proteins c-bcl-2/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , Receptors, Estrogen/drug effects , Receptors, Estrogen/metabolism , Receptors, Progesterone/drug effects , Receptors, Progesterone/metabolism , Tumor Suppressor Protein p53/drug effects , Tumor Suppressor Protein p53/metabolism , Uterine Neoplasms/metabolism
2.
Gynecol Obstet Invest ; 61(1): 24-8, 2006.
Article in English | MEDLINE | ID: mdl-16141722

ABSTRACT

BACKGROUND/AIMS: Endometrial polyps are quite common in the general population, they have a significant role in postmenopausal bleeding, and the pathogenesis is unclear. The aim of this study was to investigate proliferation markers and expression of estrogen and progesterone receptors in endometrial polyps in postmenopausal women. METHODS: Endometrial polyps were removed by hysteroscopy from 36 women who presented with postmenopausal bleeding. None were using hormonal therapy. The control group consisted of 16 inactive-atrophic postmenopausal endometrial specimens removed at hysterectomy. Immunohistochemistry was used to demonstrate expression of estrogen and progesterone receptors and the cell growth and apoptosis markers, Ki67, bcl-2, c-erbB-2. RESULTS: In both the glandular epithelium and stroma of endometrial polyps, estrogen and progesterone receptors, Ki67 and bcl-2 showed significantly more positive staining than the inactive endometrium from the control group. There was no difference in expression of c-erbB-2 between the two groups. CONCLUSIONS: Estrogen may have a role in the development of postmenopausal endometrial polyps, either by direct stimulation of localized proliferation or by stimulation of proliferation via other pathways, such as activation of Ki67 or through inhibition of apoptosis via bcl-2. c- erbB-2 is unlikely to play any role in development of these lesions.


Subject(s)
Biomarkers, Tumor/analysis , Endometrium/metabolism , Polyps/metabolism , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Uterine Diseases/metabolism , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Middle Aged , Polyps/pathology , Postmenopause , Proto-Oncogene Proteins c-bcl-2/analysis , Receptor, ErbB-2/analysis , Treatment Outcome , Uterine Diseases/pathology
3.
J Reprod Med ; 49(7): 575-7, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15305833

ABSTRACT

BACKGROUND: Different types of fibroids may affect reproductive outcome to a different extent, causing infertility and pregnancy wastage. Rectosigmoid compression, prolapse of a pedunculated submucous tumor through the cervix, venous stasis, polycythemia and ascites are infrequently associated with leiomyomas. Uterine leiomyomas arefound in approximately 2% of pregnant women; 1 in 10 causes complications during pregnancy. CASE: A 37-year-old woman, gravida 3, para 2, abortion 0, at 18 weeks of pregnancy, arrived at our outpatient clinic with a complaint of leaking vaginal fluid. On examination, a prolapsed, pedunculated myoma, measuring 5 x 6 x 7 cm, and pooling of amniotic fluid in the vaginal fornix were detected. Antibiotics were started, but the amniotic fluid leak continued, and the fetal heart beat became undetectable after 12 hours of hospitalization. We tried to excise the myoma from the vagina but because it was very large, we could not reach the proximal point it originatedfrom. We dissected the posterior cervical channel, removed the myoma and performed a total abdominal hysterectomy. CONCLUSION: Vaginal myomectomy is recommended as the initial treatment of choicefor a prolapsed, pedunculated submucous myoma except when other indications necessitate an abdominal approach. Use of Laminaria and hysteroscopic resection has been mentioned as other treatment choices. In our case a prolapsed, pedunculated cervical myoma was detected along with pregnancy complications, preterm premature rupture of membranes and fetal death. The cause-and-effect relationship between the prolapsed myoma and membrane rupture is unknown. We were unable to perform a vaginal or abdominal myomectomy because the myoma originated in the posterior cervical region, so we had to perform an abdominal hysterectomy.


Subject(s)
Fetal Death/etiology , Fetal Membranes, Premature Rupture/complications , Myoma/surgery , Pregnancy Complications, Neoplastic , Uterine Cervical Neoplasms/surgery , Abortion, Induced/methods , Adult , Female , Fetal Death/surgery , Humans , Hysterectomy/methods , Myoma/complications , Pregnancy , Prolapse , Uterine Cervical Neoplasms/complications
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