APPROACHES TO THE REPLACEMENT OF ETHINYLESTRADIOL BY NATURAL 17-BETA-ESTRADIOL IN COMBINED ORAL-CONTRACEPTIVES

The strong hepatic estrogenic actions of ethinylestradiol (EE) are ver y likely to be the cause of the cardiovascular morbidity related to th e use of combined oral contraceptives (COCs). This survey presents res ults of EE replacement in COCs with natural 171 beta-estradiol (E2) in the following stages: reduction of EE to daily doses of 0.01 mg and c oncomitant replacement with E2 las valerate, EV), complete replacement of EE with E2 using a novel multiphasic combination containing EV and the progestin dienogest (DNG), and the use of natural E2 to develop e strogen sulfamates (J 995) showing sufficient dissociation of uterine from liver estrogenicity. Recent data from preclinical and clinical st udies show that these approaches seem to be promising.