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

Yukio Katsuki, Yukiko Takano, Yoshihiro Futamura, Yasunori Shibutani, Daisuke Aoki, Yasuhiro Udagawa, Shiro Nozawa

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)


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 fluids cells, and decreased interleukin-1β production by peritoneal macrophages. In contrast, danazol (100 mg/kg per day, p.o.) and buserelin (30 μg/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 μg/kg per day) suppressed the bone mineral loss induced by buserelin alone, with no reduction of the effect of 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.

Original languageEnglish
Pages (from-to)216-226
Number of pages11
JournalEuropean journal of endocrinology
Issue number2
Publication statusPublished - 1998 Feb

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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