Terakawa N
Department of Obstetrics and Gynecology, Osaka University Medical School.
Nihon Sanka Fujinka Gakkai Zasshi. 1989 Aug;41(8):981-9; discussion 1000-7.
GnRH agonist and synthetic steroid such as Danazol, Medroxyprogesterone acetate (MPA) and Gestrinone are useful for the treatment of patients with endometriosis. These compounds induce atrophy and regression of endometriotic tissue, but the action mechanisms are still unclear. The present study, therefore, was undertaken to elucidate the mechanisms of these compounds in the treatment of endometriosis. In addition, a combination therapy with these compounds for endometriosis was also evaluated with an experimental animal model. Effects of GnRH agonist, Danazol and GnRH/Danazol combination on experimental endometriosis were evaluated in female rats. Endometrium autotransplanted under the renal capsule markedly decreased in size following castration. Histologic examination indicated atrophy and regression of the endometrial explant. The changes of endometrial explant were also induced by GnRH agonist, Danazol and combination treatment. However, a combination therapy with GnRH agonist and Danazol (93%) was shown to be superior to GnRH agonist (65%) and Danazol alone (45%) to induce atrophy and regression of experimental endometriosis. As expected, GnRH agonist significantly decreased serum E2, but Danazol did not at all. It is suggested that a combination therapy with GnRH agonist and Danazol may be a potential modality in the treatment of endometriosis. In order to evaluate whether Danazol, MPA, and Gestrinone has a direct inhibitory effect to synthesize estrogen, immature female rats were hypophysectomized and the ovaries were stimulated by a daily PMS injection. Administration of Danazol to the rats for two weeks stimulated the synthesis of 17, 20-lyase, 17 beta-HSD and aromatase activity, but did not inhibit any enzyme activities.(ABSTRACT TRUNCATED AT 250 WORDS)
促性腺激素释放激素(GnRH)激动剂以及合成类固醇,如达那唑、醋酸甲羟孕酮(MPA)和孕三烯酮,对子宫内膜异位症患者的治疗有效。这些化合物可诱导异位内膜组织萎缩和消退,但其作用机制仍不清楚。因此,本研究旨在阐明这些化合物治疗子宫内膜异位症的机制。此外,还利用实验动物模型评估了这些化合物联合治疗子宫内膜异位症的效果。在雌性大鼠中评估了GnRH激动剂、达那唑以及GnRH/达那唑联合用药对实验性子宫内膜异位症的影响。肾被膜下自体移植的子宫内膜在去势后体积明显减小。组织学检查显示子宫内膜外植体萎缩和消退。GnRH激动剂、达那唑及联合治疗也可诱导子宫内膜外植体发生上述变化。然而,GnRH激动剂与达那唑联合治疗(93%)在诱导实验性子宫内膜异位症萎缩和消退方面优于单独使用GnRH激动剂(65%)和达那唑(45%)。正如预期的那样,GnRH激动剂可显著降低血清雌二醇(E2)水平,但达那唑对其无影响。提示GnRH激动剂与达那唑联合治疗可能是治疗子宫内膜异位症的一种潜在方式。为了评估达那唑、MPA和孕三烯酮是否对雌激素合成具有直接抑制作用,对未成熟雌性大鼠进行垂体切除,并每日注射促卵泡成熟素(PMS)刺激卵巢。给大鼠连续两周注射达那唑可刺激17,20-裂解酶、17β-羟类固醇脱氢酶(17β-HSD)和芳香化酶活性的合成,但不抑制任何酶活性。(摘要截取自250词)