Since the introduction of the first contraceptive pill in 1959, the development of new hormonal contraceptives has focused on maintaining the benefits of oral contraceptives while reducing their... Show moreSince the introduction of the first contraceptive pill in 1959, the development of new hormonal contraceptives has focused on maintaining the benefits of oral contraceptives while reducing their adverse effects. Four approaches have been used to optimize the risk-benefit profile: (i) lowering of the steroid dose; (ii) development of new formulas and schedules of administration; (iii) development of new steroids and (iv) development of new routes of administration. The first objective of this thesis was to compare the multiphasic schedule of administration of oral contraceptives with the classic monophasic schedule of administration in terms of contraceptive effectiveness, bleeding pattern and discontinuation. The second objective was to predict the thrombotic risk of oral contraceptives containing the new steroid drospirenone by comparing the thrombin generation-based APC-resistance in users of pills containing drospirenone with the APC-resistance in users of pills containing other progestogens. We also focused on the biological basis of acquired APC-resistance in oral contraceptive users by studying the two main determinants of the thrombin generation-based APC-resistance test, free protein S and tissue factor pathway inhibitor free antigen. In addition, we tested the usefulness of sex hormone binding globulin as a new marker for the thrombotic risk of a hormonal contraceptive. The third objective was to estimate the thrombotic risk of contraceptives which administer steroids vaginally, transdermally or intrauterine by assessing the effect of these contraceptives on thrombin generation-based APC-resistance. At last we evaluated whether varying levels of estradiol and progesterone during a natural menstrual cycle are associated with differences in APC-resistance. Show less
