THE EFFECTS OF ICI-182,780, A PURE ANTIESTROGEN, ON THE HYPOTHALAMIC-PITUITARY-GONADAL AXIS AND ON ENDOMETRIAL PROLIFERATION IN PREMENOPAUSAL WOMEN

ICI 182,780 has shown pure oestrogen antagonism in vitro and in vivo i n animals. A total of 17 women with normal menstrual cycles were admin istered ICI 182,780, 12 mg daily for 7 days in the follicular phase pr ior to hysterectomy; 11 normal women were used as controls. Of the 17 patients, three (18%) experienced a luteinizing hormone (LH) surge in the treatment group compared with five (45%) in the controls (P = 0.24 ), and these patients were only included up to the surge. There were n o differences in the daily mean plasma LH and follicle stimulating hor mone concentrations between the treatment (n = 17) and control (n = 10 ) groups. The mean plasma oestradiol was higher in the treatment group than controls (P < 0.05) on days 5, 6 and 7. However, there was no in crease in endometrial thickness in the treatment group throughout the study. In the control group, endometrial thickness increased during th e study and was significantly higher (P < 0.05) on day 7. There was no ultrasonic evidence of ovarian hyperstimulation and no serious advers e events reported. This study shows that treatment for 7 days with ICI 182,780 does not cause ovarian hyperstimulation and has a potent anti -oestrogenic action on the endometrium. We conclude that ICI 182,780 m ay be a useful compound in the treatment of oestrogen-dependent gynaec ological disease.