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A combination therapy of danazol and GnRH agonist for endometriosis

Research Project

Project/Area Number 04454420
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionTottori University, Faculty of Medicine

Principal Investigator

TERAKAWA Naoki  Tottori Uni. Dept. Obstet. Gynecol., Professor, 医学部, 教授 (90163906)

Co-Investigator(Kenkyū-buntansha) HARADA Tasuku  Tottori Uni. Dept. Obstet. Gynecol., Assistant Professor, 医学部・附属病院, 助手 (40218649)
MIO Yasuyuki  Tottori Uni. Dept. Obstet. Gynecol., Assistant Professor, 医学部, 講師 (10135882)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1992: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsEndometriosis / Danazol / GnRH agonist / Combination therapy / Laparoscopy / 腹腔鏡検査
Research Abstract

Autocrine growth mechanism of endometriosis and inhibitory effects of danazol and GnRH agonist on the growth of endometriosis were investigated Danazol treatment did not show suppressive effects on hypothalamic-pituitary-pvarian axis in patients whih endometriosis. Danazol also did not inhibit estrogen production by the ovary through its direct action on the ovary. It is suggested that the inhibitory effect of danazol on the growth of endometriosis is mediated through progestin and androgen receptors in the cells. In contrast, the mechanism of action of GnRH agonist-induced resorption of endometriosis is estrogen deprivation and subsequent atrophy. GnRH agonist administration resulted in a significant suppression of the serum level of bioactive LH, of the pulsatility of LH release, and of the pituitary response to GnRH (Endocrinol Japon 39 : 615, 1992, In Vivo 7 : 127, 1993, Fertil Steril, in press).
Human endometrial adenocarcinoma cells produce angiogenic factors such as TGF-beta and … More FGF.Progestin MPA inhibited neovascularization induced by the angiogenic factors that were secreted by adenocarcinoma cells. It is possible that progestins suppress the angiogenesis in endometriosis and inhibit the progressive growth of the disease (Am J Obstet Gynecol 167 : 207, 1992, Int J Cancer 54 : 862, 1993).
Effects of Danazol, GnRH agonist, and a combination of danazol and GnRH agonist on endometriosis were evaluated in randomly assigned 66 patients. Pretreatment and post-treatment laparoscopies were compared by means of the American Fertility Society's scoring system. The mean laparoscopic scores significantly decreased with either danazol or GnRH agonist buserelin. However, the beneficial effects of the treatments in patients with Stage III or disease were not prominent. There was no statistically significant improvement with the combination therapy because the group consisted of patients with high score. It is concluded that the potential application of a combination therapy of danazol and Gnrh agonist, which shows different modes of action, in treatment of patients with advanced endometriosis should be evaluated with large scale clinical trials (Am J Obstet Gynecol 167 : 271, 1992, Fertil, in press). Less

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Jikihara H: "Inhibitory effect of medroxyprogesterone acetate on angiogenesis induced by human endometrial cancer" Am J Obstet Gynecol. 167. 207-211 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mio Y: "Luteinized unruptured follicle in the early stages of endometriosis as a cause of unexplained infertility" Am J Obstet Gynecol. 167. 271-273 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizutani T: "No inhibitory effects of gestrinone and medroxyprogesterone acetate on the estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins" Endocrinol Japon. 39. 615-621 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizutani T: "No inhibitory effects of danazol on estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins" In Vivo. 7. 127-130 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakata M: "Autocrine growth mechanism by transforming growth factor (TGF)-β_1 and TGF-β_1-receptor regulation by epidermal growth factor in a human endometrial cancer cell line IK-90" Int J Cancer. 54. 862-867 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakata M: "The hypothalamic-pituitary-ovarian axis in patients with endometriosis is suppressed by leuprolide acetate but not by danazol" Fertil Steril. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Jikihara H: "Inhibitory effect of medroxyprogesterone acetate on angiogenesis induced by human endometrial cancer" Am J Obstet Gynecol. 167(1). 207-211 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mio Y: "Luteinized unruptured follicle in the early stages of unexplained infertility" Am J Obstet Gynecol. 167(1). 271-273 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizutani T: "No inhibitory effects of gestrinone and medroxy-progesterone acetate on the estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins" Endocrinol Japon. 39(6). 615-621 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mizutani T: "No inhibitory effects of danazol on estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins" in Vivo. 7(2). 127-130 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakata M: "Autocrine growth mechanism by transforming growth factor (TGF)-beta_1 and TGF-beta_1-receptor regulation by epidermal growth factor in a human endometrial cancer cell line IK-90" Int J Cancer. 54(5). 862-867 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakata M: "The hypothalamic-pituitary-ovarian axis in patients with endometriosis is suppressed by leuprolide acetate but not by danazol" Fertil Steril. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] TAKAHIRO MIZUTANI: "No inhibitory effects of gestrinone and medroxyprogesterone acetate on the estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins" ENDOCRINOLOGIA JAPONICA. 39. 615-621 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] TAKAHIRO MIZUTANI: "No inhibitory effects of danazol on estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins" In Vivo(in press).

    • Related Report
      1992 Annual Research Report
  • [Publications] 寺川 直樹: "子宮内膜症とホルモン療法" 産婦人科治療. 64. 822-826 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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