Gonadotropin-releasing hormone agonist and danazol normalize aromatase cytochrome P450 expression in eutopic endometrium from women with endometriosis, adenomyosis, or leiomyomas.
OBJECTIVE
To investigate whether GnRH agonists or danazol therapy normalizes estrogen metabolism in the eutopic endometrium of women with endometriosis, adenomyosis, or leiomyomas.


METHODS
Prospective clinical study.


METHODS
University hospital.


METHODS
Fifty-three women with endometriosis, adenomyosis, or leiomyomas.


METHODS
Patients received GnRH agonist or danazol. Biopsy samples of the endometrium were obtained before and after endocrine therapy. Nontreated endometrial explants were cultured in the presence of either drug.


METHODS
Reverse transcription polymerase chain reaction-Southern blot and immunohistochemical analyses of the endometrial expression of aromatase cytochrome P450, estrogen receptor, progesterone receptor, and Ki-67. Nontreated endometrial explants were cultured in the presence of either drug.


RESULTS
Messenger RNA and protein of aromatase cytochrome P450 were greatly reduced in the eutopic endometrium of patients treated with GnRH agonist for 2 months or more or with danazol for 1 month or more. Culture of endometrial explants with GnRH agonist (10(-9)-10(-7) M) did not change the amount of aromatase cytochrome P450, whereas danazol (10(-7)-10(-6) M) efficiently reduced aromatase cytochrome P450 expression.


CONCLUSIONS
Therapy with GnRH agonist or danazol decreases expression of aromatase cytochrome P450 in diseased eutopic endometrium. Endocrine therapy normalized in part the impaired hormonal expression of the eutopic endometrium. GnRH agonist reduced aromatase cytochrome P450 expression mainly by promoting a hypoestrogenic state, whereas danazol reduced aromatase cytochrome P450 in part by direct action on the eutopic endometrium.
Ishihara
Hiroaki
H
Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kitawaki
Jo
J
Kado
Noriko
N
Koshiba
Hisato
H
Fushiki
Shinji
S
Honjo
Hideo
H
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D002064:Buserelin / Q000494:pharmacology; D003613:Danazol / Q000494:pharmacology*; D004715:Endometriosis / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D066298:In Vitro Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D007889:Leiomyoma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D016729:Leuprolide / Q000494:pharmacology; D008875:Middle Aged; D011446:Prospective Studies; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014591:Uterine Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D004967:Estrogens; D019394:Ki-67 Antigen; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone; D001141:Aromatase; D016729:Leuprolide; D003613:Danazol; D002064:Buserelin