Effect of Gonadotropin-Releasing Hormone Agonist Treatment upon Angiogenesis in Uterine Leiomyoma

Objective: To assess the effect of gonadotropin-releasing hormone (GnRH) agonist treatment upon angiogenesis in uterine leiomyomata. Methods: Uterine leiomyomata specimens of 49 consecutive patients who underwent myomectomy or hysterectomy following presurgical treatment with (n = 23) and without (n = 26) GnRH agonist were stained immunohistochemically with antibody to factor VIII-related antigen. For each subject, age, parity, number of Lupron treatments, leiomyoma size (cm), and mean microvessel counts calculated from three fields (×400) were recorded. Differences in patient age, parity, microvessel counts and leiomyoma size between GnRH agonist treated and untreated patients were tested by unpaired Student’s t test. Differences among the various number of doses were tested by one-way ANOVA, with Bonferonni and Neuman-Keuls post hoc tests between specific dose-number groups. The relationship between microvessel counts and leiomyoma size was tested by Pearson correlation test. Multivariate stepwise regression tested the relationship between the number of Lupron doses and microvessel counts, correcting for age, parity, and leiomyoma size. p < 0.05 was considered significant. Results: Patient age and parity were similar in GnRH treated and untreated patients (mean 43.3 ± 6.6 versus 43.9 ± 7.5 years and median 2 (range 0–7) versus 1 (range 0–5), p = 0.78 and p = 0.45, respectively). Microvessel counts of leiomyomata specimens treated presurgically with GnRH agonist therapy (median 22.7, range 6.7–65.7) were not significantly different from microvessel counts of specimens without presurgical GnRH agonist treatment (median 19.8, range 6–53; p = 0.77). No correlation between leiomyoma size and microvessel counts was noted (r = 0.06, P = 0.7). Conclusion: Angiogenesis as assessed by microvessel counts in surgically removed leiomyomata is not affected by presurgical medical management with GnRH agonist therapy.

[1]  B. Mızrak,et al.  GnRH agonist decreases endothelial nitric oxide synthase (eNOS) expression in leiomyoma , 2000, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[2]  N. Terada,et al.  Suppression of cell proliferation and induction of apoptosis in uterine leiomyoma by gonadotropin-releasing hormone agonist (leuprolide acetate). , 1998, The Journal of clinical endocrinology and metabolism.

[3]  R. Tarnuzzer,et al.  Differential expression of matrix metalloproteinases and their tissue inhibitors in leiomyomata: a mechanism for gonadotrophin releasing hormone agonist-induced tumour regression. , 1997, Molecular human reproduction.

[4]  B. Quade,et al.  Expression of the fibroblast growth factor receptor in women with leiomyomas and abnormal uterine bleeding. , 1997, Molecular human reproduction.

[5]  C. H. Liu,et al.  Enhanced deoxyribonucleic acid damage and repair but unchanged apoptosis in uterine leiomyomas treated with gonadotropin-releasing hormone agonist. , 1997, American journal of obstetrics and gynecology.

[6]  E. Vamvakas,et al.  Histology of Leiomyomata in Patients Treated with Leuprolide Acetate , 1997, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[7]  R. Tarnuzzer,et al.  Suppression of transforming growth factor-beta (TGF beta) and TGF beta receptor messenger ribonucleic acid and protein expression in leiomyomata in women receiving gonadotropin-releasing hormone agonist therapy. , 1996, The Journal of clinical endocrinology and metabolism.

[8]  D. Redmer,et al.  Angiogenesis in the ovary. , 1996, Reviews of reproduction.

[9]  C. Chou,et al.  Intratumoral Blood Flow in Uterine Myoma Correlated With a Lower Tumor Size and Volume, but not Correlated With Cell Proliferation or Angiogenesis , 1996, Obstetrics and gynecology.

[10]  C. Spong,et al.  Leuprolide Acetate Treatment and Myoma Arterial Size , 1995, Obstetrics and gynecology.

[11]  J. Crow,et al.  Morphological changes in uterine leiomyomas treated by GnRH agonist goserelin. , 1995, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[12]  R. Barbieri,et al.  Progesterone: A critical role in the pathogenesis of uterine myomas , 1995, American journal of obstetrics and gynecology.

[13]  O. Kletzky,et al.  Absence of a dose-response effect of leuprolide acetate on leiomyomata uteri size. , 1994, Fertility and sterility.

[14]  H. Peterson,et al.  Hysterectomy in the United States, 1988‐1990 , 1994, Obstetrics and gynecology.

[15]  A. Lindenmayer,et al.  Endothelial cell markers CD31, CD34, and BNH9 antibody to H- and Y-antigens--evaluation of their specificity and sensitivity in the diagnosis of vascular tumors and comparison with von Willebrand factor. , 1994, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[16]  T. Colgan,et al.  The histopathology of uterine leiomyomas following treatment with gonadotropin-releasing hormone analogues. , 1993, Human pathology.

[17]  J. D. Miller,et al.  Treatment of leiomyomata uteri with leuprolide acetate depot: A double‐blind, placebo‐controlled, multicenter study , 1991, Obstetrics and gynecology.

[18]  P. Googe,et al.  Histopathological changes in leiomyomata treated with leuprolide acetate. , 1990, Fertility and sterility.

[19]  B. Vollenhoven,et al.  Uterine fibroids: A clinical review , 1990, British journal of obstetrics and gynaecology.

[20]  R. Shaw Mechanism of LHRH analogue action in uterine fibroids. , 1989, Hormone research.

[21]  J. Folkman,et al.  How is blood vessel growth regulated in normal and neoplastic tissue? G.H.A. Clowes memorial Award lecture. , 1986, Cancer research.

[22]  E. Wallach,et al.  Uterine leiomyomata: etiology, symptomatology, and management. , 1981, Fertility and sterility.

[23]  T. K. Hunt,et al.  Regulation of wound-healing angiogenesis-effect of oxygen gradients and inspired oxygen concentration. , 1981, Surgery.

[24]  R. Auerbach,et al.  Lymphocyte-induced angiogenesis: a quantitative and sensitive assay of the graft-vs.-host reaction , 1975, The Journal of experimental medicine.