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 journalArticle

60 Citations (Scopus)

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 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
Volume138
Issue number2
DOIs
Publication statusPublished - 1998 Feb

Fingerprint

dienogest
Endometriosis
Steroids
Buserelin
Danazol
Ascitic Fluid
Minerals
Immune System
Bone and Bones
Autologous Transplantation
Peritoneal Macrophages
Oral Contraceptives
Endometrium
Interleukin-1
Gonadotropin-Releasing Hormone
Protein Kinase C

ASJC Scopus subject areas

  • Endocrinology

Cite this

Katsuki, Y., Takano, Y., Futamura, Y., Shibutani, Y., Aoki, D., Udagawa, Y., & Nozawa, S. (1998). Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats. European Journal of Endocrinology, 138(2), 216-226. https://doi.org/10.1530/eje.0.1380216

Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats. / Katsuki, Yukio; Takano, Yukiko; Futamura, Yoshihiro; Shibutani, Yasunori; Aoki, Daisuke; Udagawa, Yasuhiro; Nozawa, Shiro.

In: European Journal of Endocrinology, Vol. 138, No. 2, 02.1998, p. 216-226.

Research output: Contribution to journalArticle

Katsuki, Y, Takano, Y, Futamura, Y, Shibutani, Y, Aoki, D, Udagawa, Y & Nozawa, S 1998, 'Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats', European Journal of Endocrinology, vol. 138, no. 2, pp. 216-226. https://doi.org/10.1530/eje.0.1380216
Katsuki, Yukio ; Takano, Yukiko ; Futamura, Yoshihiro ; Shibutani, Yasunori ; Aoki, Daisuke ; Udagawa, Yasuhiro ; Nozawa, Shiro. / Effects of dienogest, a synthetic steroid, on experimental endometriosis in rats. In: European Journal of Endocrinology. 1998 ; Vol. 138, No. 2. pp. 216-226.
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