Preoperative treatment of uterine leiomyomas: clinical findings and expression of transforming growth factor-beta3 and connective tissue growth factor.
OBJECTIVE
To evaluate the clinical features and the expression of transforming growth factor-beta3 (TGF-beta3) 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 patients 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-beta3 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-beta3 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.


CONCLUSIONS
This study focuses on the effects of GnRH-a and tibolone on TGF-beta3 and CTGF expression in myometrium and myomas and supports the hypothesis of a pathogenetic role of these growth factors in uterine fibromatosis.
De Falco
Marianna
M
Dipartimento di Scienze Ostetrico-Ginecologiche, Urologiche e Medicina della Riproduzione, Universitá degli Studi di Napoli Federico II, Napoli, Italia.
Staibano
Stefania
S
D'Armiento
Francesco Paolo
FP
Mascolo
Massimo
M
Salvatore
Gaetano
G
Busiello
Anna
A
Carbone
Ilma Floriana
IF
Pollio
Fabrizio
F
Di Lieto
Andrea
A
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D055513:Connective Tissue Growth Factor; D004359:Drug Therapy, Combination; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D019584:Hot Flashes / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000378:metabolism*; D007501:Iron / Q000097:blood; D007889:Leiomyoma / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D016729:Leuprolide / Q000627:therapeutic use*; D009215:Myometrium / Q000378:metabolism; D020360:Neoadjuvant Therapy; D009652:Norpregnenes / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D053782:Transforming Growth Factor beta3; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery
D018931:Antineoplastic Agents, Hormonal; C526317:CCN2 protein, human; D006454:Hemoglobins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009652:Norpregnenes; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D055513:Connective Tissue Growth Factor; D007501:Iron; D016729:Leuprolide; C027385:tibolone