Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats

Y Katsuki, Yukio Katsuki, Yuko Takano, Y Takano, Yoshihiro Futamura, Y Futamura, Yasunori Shibutani, Y Shibutani, Dai Aoki, D Aoki, Yasuhiro Udagawa, Y Udagawa, S Nozawa
European journal of endocrinology · 1998 · vol. 138(2) , pp. 216–226 · doi:10.1530/eje.0.1380216 · PMID:9506869 · W2115466905
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Dienogest reduced endometrial implant volume and modulated immune responses in rats, demonstrating antiproliferative and progestational effects distinct from danazol and GnRH agonists.

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Abstract

OBJECTIVE: Dienogest, a synthetic steroid with progestational activity, is used as a component of oral contraceptives and is currently being evaluated clinically for the treatment of endometriosis. The present study was conducted to confirm the effects of dienogest on experimental endometriosis in rats and to elucidate its mechanism of action. DESIGN: Experimental endometriosis induced by autotransplantation of endometrium in rats. METHODS: Endometrial implants, immune system, and bone mineral were investigated after 3 weeks of medication. RESULTS: Dienogest (0.1-1 mg/kg per day, p.o.) reduced the endometrial implant volume to the same extent as danazol (100 mg/kg per day, p.o.). Simultaneously, dienogest ameliorated the endometrial implant-induced alterations of the immune system: i.e. it increased the natural killer activity of peritoneal fluid cells and splenic cells, decreased the number of peritoneal fluid cells, and decreased interleukin-1beta production by peritoneal macrophages. In contrast, danazol (100 mg/kg per day, p.o.) and buserelin (30 microg/kg per day, s.c.) had none of these immunologic effects. Additionally, combined administration of dienogest (0.1 mg/kg per day) plus buserelin (0.3 microg/kg per day) suppressed the bone mineral loss induced by buserelin alone, with no reduction of the effect on endometrial implants. In vitro studies on dienogest revealed an antiproliferative effect on rat endometrial cells due to inhibition of protein kinase C activity plus a partial progestational effect. CONCLUSIONS: Dienogest appears to be a potent agent with mechanisms of action different from those of danazol and GnRH agonists currently available for the treatment of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Nandrolone Progesterone Congeners Animals Buserelin Buserelin Cell Division Cell Division Cyclic AMP Cyclic AMP Cyclic AMP-Dependent Protein Kinases Cyclic AMP-Dependent Protein Kinases Cytotoxicity, Immunologic Cytotoxicity, Immunologic Danazol Danazol Disease Models, Animal Endometriosis Enzyme Inhibitors Enzyme Inhibitors

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