The effects of ICI 182,780, a pure anti-oestrogen, on the hypothalamic-pituitary-gonadal axis and on endometrial proliferation in pre-menopausal women.
ICI 182,780 has shown pure oestrogen antagonism in vitro and in vivo in animals. A total of 17 women with normal menstrual cycles were administered ICI 182,780, 12 mg daily for 7 days in the follicular phase prior 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 no differences in the daily mean plasma LH and follicle stimulating hormone 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 increase in endometrial thickness in the treatment group throughout the study. In the control group, endometrial thickness increased during the study and was significantly higher (P < 0.05) on day 7. There was no ultrasonic evidence of ovarian hyperstimulation and no serious adverse 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 may be a useful compound in the treatment of oestrogen-dependent gynaecological disease.
Thomas
E J
EJ
University of Southampton, Princess Anne Hospital.
Walton
P L
PL
Thomas
N M
NM
Dowsett
M
M
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D004717:Endometrium / Q000166:cytology / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005498:Follicular Phase; D000077267:Fulvestrant; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D006080:Ovarian Follicle / Q000187:drug effects / Q000502:physiology; D010053:Ovary / Q000187:drug effects* / Q000502:physiology; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D017697:Premenopause
D004965:Estrogen Antagonists; D000077267:Fulvestrant; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone