Antiuterotrophic effects of the pure antioestrogen ICI 182,780 in adult female monkeys (Macaca nemestrina): quantitative magnetic resonance imaging.
The antiuterotrophic efficacy of the pure antioestrogen ICI 182,780 has been demonstrated previously by magnetic resonance imaging (MRI) in ovariectomized oestrogen-treated monkeys (Macaca nemestrina). Further characterization of the effects of ICI 182,780 in intact adult female monkeys with normal menstrual cycles was undertaken to provide an indication of its potential actions in premenopausal women. Changes in the volume of uterine tissues were measured by MRI in early, mid and late cycle. The volume of the uterus varied up to fivefold between individual monkeys but serial observations in individuals provided sufficient precision to allow accurate assessments to be made of changes in the endometrium and myometrium during the course of the menstrual cycle and following ICI 182,780 administration. In comparison with its initial size in untreated monkeys, the endometrium increased in volume by 60% and 125% in the mid and late cycle respectively. In contrast, the size of the myometrium decreased significantly, by 16% from early to mid cycle and then recovered to near its initial volume in the late cycle. Treatment with ICI 182,780 beginning in the early part of the menstrual cycle prevented the growth of the uterus. The magnitude and duration of the response was dependent on whether or not ovulation occurred during treatment with ICI 182,780. In animals rendered anovulatory, growth of the endometrium was blocked completely by ICI 182,780 and the volume of the tissue declined below that present at the start of the menstrual cycle. Antiuterotrophic efficacy was significantly less in monkeys which ovulated during treatment with ICI 182,780.(ABSTRACT TRUNCATED AT 250 WORDS)
Dukes
M
M
Cancer Research Department, ZENECA Pharmaceuticals, Macclesfield, Cheshire, U.K.
Waterton
J C
JC
Wakeling
A E
AE
D000818:Animals; D004717:Endometrium / Q000033:anatomy & histology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D008254:Macaca nemestrina; D008279:Magnetic Resonance Imaging; D008597:Menstrual Cycle; D009215:Myometrium / Q000033:anatomy & histology; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects*
D004965:Estrogen Antagonists; D000077267:Fulvestrant; D004958:Estradiol