[Studies on endocrine therapy of endometriosis].
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)
Terakawa
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Department of Obstetrics and Gynecology, Osaka University Medical School.
D000818:Animals; D002064:Buserelin / Q000627:therapeutic use; D003613:Danazol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004715:Endometriosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004958:Estradiol / Q000096:biosynthesis / Q000097:blood; D005260:Female; D005867:Gestrinone / Q000494:pharmacology / Q000627:therapeutic use; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D016729:Leuprolide; D007986:Luteinizing Hormone / Q000378:metabolism; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D017258:Medroxyprogesterone Acetate; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D011245:Pregnadienes / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D011245:Pregnadienes; D005867:Gestrinone; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone; D017258:Medroxyprogesterone Acetate; D016729:Leuprolide; D008525:Medroxyprogesterone; D003613:Danazol; D002064:Buserelin