Use this URL to cite or link to this record in EThOS:
Title: Towards developing a new contraceptive pill : effects of mifepristone on reproductive tissues and menstrual cycle
Author: Narvekar, N. N.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
The first study investigates the effect of daily low-dose mifepristone on proliferation markers [phospho-histone H3 (pH3) mitosis marker] and steroid receptors [oestrogen receptor, progesterone receptor, androgen receptor (AR)] in the endometrium. There was a significant down-regulation in pH3 and PR expression following mifepristone treatment whereas AR expression was up-regulated. Since androgens antagonize oestrogen-effects on the endometrium, mifepristone-induced AR up-regulation could play a role in its anti-proliferative effects. The second study investigates the effects of daily low-dose mifepristone on endometrial parameters [microvasculature, vascular endothelial growth factor (VEGF) and glucocorticoid receptor (GR)]. The majority (15/16) of subjects were amenorrhoeic, mean oestradiol concentrations remained in the mid-proliferative range and most (9/16 subjects) endometrial samples showed proliferative histology. GR expression was induced in the nuclei of glands and surface (luminal) epithelium and there was a significant increase in micro-vessel density and decrease in stromal VEGF following treatment. Glucocorticoids can modulate angiogenesis and the high incidence of mifepristone-induced amenorrhoea may be related to change in the regulation of vascular function. The third study investigates the effects of daily low-dose mifepristone on vaginal morphology, histology, steroid receptor and Serine Leukocyte Protease Inhibitor (SLPI) content. There was no change in vaginal thickness, steroid receptor and SLPI content and distribution following mifepristone treatment. The absence of changes, in contrast to other oestrogen-free hormonal contraception, is reassuring. The fourth study investigates the effect of three single doses of mifepristone on menstrual cycle and the feasibility of timing administration as a once-month-contraceptive pill based on the length of previous menstrual cycles (calendar). It is not possible to use the calendar approach to identify the correct time of administration of mifepristone and mifepristone disrupts menstruation in a dose-dependent manner.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available