Title:
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Contraceptive and endometrial aspects of progestins and anti-progestins
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The main focus of the studies undertaken as a part of this thesis was to develop new methods of contraception, while broadening our current understanding of the antifertility potentials of two progesterone receptor modulators: antiprogesterone compound mifepristone, and the synthetic progestin Levonorgestrel (LNG). We suggest that LNG taken immediately before ovulation acts as an emergency contraceptive (EC) by delaying or preventing ovulation. We have demonstrated that the combination of a home-use fertility monitor with once a month administration of mifepristone (especially if mifepristone is administered at the early luteal phase) is an acceptable contraceptive option with minimal side effects. Our investigations have explained some characteristics of non-compliant behaviour. We have shown that the microelectronic monitoring systems provide objective information no other monitoring technique can produce. This information offers the opportunity to make the optimum use of potentially effective treatments while validating research evidence. We have further illustrated, that this microelectronic system of Luteinizing Hormone (LH) detection can replace laboratory assays in monitoring frequently changing hormone levels in contraceptive research because it is easy to use and provides reliable data on compliance. Finally, we conclude that mifepristone induce endometrial-shedding & vaginal bleeding, in the mid-luteal phase by a mechanism involving both Prostaglandin Dehydrogenase (PGDH) and Cyclo-oxygenase - 2 (COX-2) to increase local Prostaglandin (PG) levels in the endometrium. These studies provide information which will be useful in the development of novel methods of contraception involving a "once a month" pill.
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