Comparative studies of the ethynyl estrogens used in oral contraceptives: II. Antiovulatory potency

Abstract

The occurrence or inhibition of ovulation was inferred from the plasma progestin level measured in the last week of 430 control cycles and of 4,638 cycles from fertile women receiving various antiovulatory steroids, singly and in combination. The substances tested included: mestranol and ethynylestradiol (EE) of homogeneous bioavailability, used alone in a range from 50 to 100 μg per day; these same dose levels combined with various progestins; and finally various proprietary combination and sequential low-dose regimens undergoing clinical trials. Statistical analysis showed ethynylestradiol and mestranol alone to be equipotent over the tested range, although at 50 μg per day superiority of mestranol over EE was suggested. Two preparations of EE at 50 μg per day, one of them a sequential with dimethisterone, showed different potency. At 50 μg per day no estrogen, alone or with a sequential progestin, reached a satisfactory level of effectiveness. However, very small amounts in the range of 20 to 40 μg per day were highly effective when combined with quantities of various 19-nor progestins which by themselves are well below the antiovulatory level. This indicates that a synergism exists between these two classes of compounds insofar as their antiovulatory effect is concerned, thus explaining the high contraceptive effectiveness observed with very-low-dose combination regimens.