EFFECTS OF DIENOGEST, A SYNTHETIC STEROID, ON EXPERIMENTAL ENDOMETRIOSIS IN RATS

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. Thee present study was conducted to confirm the effects of dienogest on experiment al endometriosis in rats and to elucidate its mechanism of action. Des ign: Experimental endometriosis induced by autotransplantation of endo metrium in rats. Methods: Endometrial implants, immune system, and bon e mineral were investigated after 3 weeks of medication. Results: Dien ogest (0.1-1mg/kg per day, p.o.) reduced the endometrial implant volum e to the same extent as danazol (100 mg/kg per day, p.o.). Simultaneou sly, dienogest ameliorated the endometrial implant-induced alterations of the immune system: i.e. it increased the natural killer activity o f peritoneal fluid cells and splenic cells, decreased the number of pe ritoneal fluid cells, and decreased interleukin-1 beta production by p eritoneal macrophages. In contrast, danazol (100 mg/kg per day, p.o.) and buserelin (30 mu g/kg per day, s.c.) had none of these immunologic effects. Additionally, combined administration of dienogest (0.1 mg/k g per day) plus buserelin (0.3 mu g/kg per day) suppressed the bone mi neral loss induced by buserelin alone, with no reduction of the effect on endometrial implants. In vitro studies on dienogest revealed an an tiproliferative effect on rat endometrial cells due to inhibition of p rotein kinase C activity plus a partial progestational effect. Conclus ions: 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.