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Title: The effect of antiprogestins on the endometrium and menstrual cycle
Author: Cameron, Sharon Tracey
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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The aim of this thesis was to investigate the effects of antiprogestins on the endometrium and menstrual cycle. When the antiprogestin mifepristone was given to women in a daily dose of 2 mg/day for 30 days, ovulation was either inhibited or delayed. In those women in whom ovulation was suppressed, it would appear that mifepristone prevented the positive feedback effect of oestradiol as no LH surge occurred in spite of preovulatory levels of oestradiol. The main site of action of the antiprogestin in this respect would appear to be the pituitary as there was no significant change in the frequency or amplitude of LH pulses during treatment. Even when ovulation did occur during treatment, the development of a secretory endometrium was delayed. Endometrial biopsies taken from two such subjects, one and four days after a plasma LH surge, were devoid of early secretory changes which would usually be expected at this stage of a normal cycle indicating that during treatment with mifepristone implantation would be unlikely to be successful. In women in whom ovulation was inhibited, follicle growth continued and the persistent follicle developed into a functional or non-functional cyst. Although the endometrium in these cases was exposed to the effects of high levels of unopposed oestrogen, there were no mitoses and no evidence of hyperplasia. Some immunostaining for the cell proliferation markers Ki67 and PCNA could however be detected. Since these markers detect the presence of cells throughout all phases of the cell cycle it is possible that mifepristone affects the entry of cells into the mitotic phase of the cell cycle and may therefore prevent endometrial hyperlasia. Administration of a single dose of the antiprogestin onapristone (400 mg) or mifepristone (200 mg) in the early luteal phase (LH+2) delayed the development of a secretory endometrium.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available