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Preoperative Treatment of Uterine Leiomyomas: Clinical Findings and Expression of Transforming Growth Factor-ß3 and Connective Tissue Growth Factor

Stefania Staibano, MD

Francesco Paolo D'Armiento, MD

Massimo Mascolo, MD

Gaetano Salvatore, MD

Anna Busiello, MD

Ilma Floriana Carbone, MD

Fabrizio Pollio, MD

Dipartimento di Scienze Osterico-Ginecologiche, Urologiche e Medicina della Riproduzione, and the Dipartimento di Scienze Biomorfologiche e Funzionali, Universitá degli Studi di Napoli "Federico II," Napoli, Italia

Andrea Di Lieto, MD,PhD

Dipartimento di Scienze Osterico-Ginecologiche, Urologiche e Medicina della Riproduzione, and the Dipartimento di Scienze Biomorfologiche e Funzionali, Universitá degli Studi di Napoli "Federico II," Napoli, Italia; dilieto{at}unina.it

Objective: To evaluate the clinical features and the expression of transforming grwoth factor-ß3 (TGF-ß3) and connective tissue growth factor (CTGF) in myometrium and uterine leiomyomas after preoperative treatment with gonadotropin-releasing hormone-analogs (GnRH-a) and tibolone.

Methods: Twenty-three patients received 3.75 mg leuprolide acetate depot for 4 months. Twenty-two ptients received the same therapy plus 2.5 mg tibolone daily. Patients underwent uterine surgery after therapy. Twenty-two untreated patients underwent surgery directly. Hematologic tests, bone mineral density (BMD) measurement, and ultrasonographic evaluation of uterine volume were performed before and after treatment. Menorrhagia and pelvic pain were evaluated with a visual analog scale. Hot flushes were recorded in daily diaries. Immunohistochemical expression of TGF-ß3 and CTGF in myometrium and myoma samples was evaluated semiquantitatively.

Results: After therapy, hemoglobin and iron levels similarly increased in both groups. BMD significantly decreased only in the GnRH-a group. Uterine volume similarly decreased in both groups. No patient had menorrhagia or pelvic pain at the end of therapy. The number of hot flushes increased after the first month in the GnRH-a group; in the GnRH-a plus tibolone group, it remained constant and was lower. In untreated cases, TGF-ß3 and CTGF smooth muscle cell immunoexpression was lower in myometrium than in leiomyomas. After medical treatment, growth factor immunoexpression remained unchanged in myometrial samples and was reduced in leiomyomas. Endothelial cells showed strong immunopositivity, both in untreated and in treated cases.

Conclusion: This study focuses on the effects of GnRH-a and tibolone on TGF-ß3 and CTGF expression in myometrium and myomas and supports the hypothesis of a pathogenetic role of these growth factors in uterine fibromatosis.

Key Words: Uterine leiomyomas • GnRH-analog • Tibolone • TGF-ß3 • CTGF

Journal of the Society for Gynecologic Investigation, Vol. 13, No. 4, 297-303 (2006)
DOI: 10.1016/j.jsgi.2006.02.008


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