A combination therapy of danazol and GnRH agonist for endometriosis

达那唑与GnRH激动剂联合治疗子宫内膜异位症

• 批准号: 04454420
• 负责人: TERAKAWA Naoki
• 金额: $ 2.82万
• 依托单位: Tottori University, Faculty of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454420/
• 关键词: Endometriosis; Danazol; GnRH agonist; Combination therapy; Laparoscopy; 腹腔鏡検査

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

探讨子宫内膜异位症的自分泌生长机制及达那唑和促性腺激素释放激素激动剂对子宫内膜异位症生长的抑制作用。达那唑对子宫内膜异位症患者的下丘脑-垂体-卵巢轴无抑制作用。丹那唑也不会通过直接作用于卵巢来抑制卵巢产生雌激素。提示达那唑对子宫内膜异位症的抑制作用是通过细胞内孕激素和雄激素受体介导的。相反，促性腺激素释放激素激动剂诱导子宫内膜异位症吸收的作用机制是雌激素剥夺和随后的萎缩。给予促性腺激素释放激素激动剂可显著抑制血清中具有生物活性的促黄体生成素水平、促黄体生成素释放的脉动性以及对促性腺激素释放激素的反应。人子宫内膜腺癌细胞产生血管生成因子，如转化生长因子-β和…更多的FGF、Progestin、MPA抑制由腺癌细胞分泌的血管生成因子诱导的新生血管形成。孕激素有可能抑制子宫内膜异位症的血管生成并抑制疾病的进展(Am J Obstet妇女167：207,1992，Int J癌症54：862,1993)。随机分配66例患者，观察丹那唑、促性腺激素释放激素激动剂及其联合用药对子宫内膜异位症的影响。通过美国生育协会的评分系统对治疗前后的腹腔镜术进行比较。达那唑或促性腺激素释放激素激动剂布塞林均可显著降低腹腔镜术后的平均评分。然而，这些治疗对III期或疾病患者的益处并不显著。联合治疗没有统计学意义的改善，因为这组患者得分很高。结论：达那唑和促性腺激素释放激素激动剂联合治疗晚期子宫内膜异位症的疗效有待大规模临床试验(Am J Obstet Gynecol 167：271,1992，Fertil，正在出版中)进行评估。较少

项目成果

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)

Sakata M：“人子宫内膜癌细胞系 IK-90 中表皮生长因子通过转化生长因子 (TGF)-β_1 和 TGF-β_1 受体调节的自分泌生长机制”Int J Cancer 54. 862-867 (1993)。

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)

Mizutani T：“孕三烯酮和醋酸甲羟孕酮对促性腺激素刺激的垂体切除大鼠卵巢产生雌激素没有抑制作用”Endocrinol Japon。

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)

TAKAHIRO MIZUTANI：“孕三烯酮和醋酸甲羟孕酮对促性腺激素刺激的垂体切除大鼠卵巢产生雌激素没有抑制作用”ENDOCRINOLOGIA JAPONICA。

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

Jikihara H：“醋酸甲羟孕酮对人类子宫内膜癌诱导的血管生成的抑制作用”Am J Obstet Gynecol。

Mizutani T: "No inhibitory effects of danazol on estrogen production by ovaries of hypophysectomized rats stimulated by gonadotropins" In Vivo. 7. 127-130 (1993)

Mizutani T：“达那唑对促性腺激素刺激的垂体切除大鼠的卵巢产生雌激素没有抑制作用”。