Plasma levels of ethinylestradiol (EE) during cyclic treatment with combined oral contraceptives.

The purpose of the present study was to extend the still limited data concerning ethinylestradiol (EE) plasma levels after repeated daily ingestion of a combination pill during the course of classical cyclic treatment. Plasma EE levels were followed in 13 volunteers throughout, in total, 19 treatment cycles with either a 50 ug EE (+ 125ug d-norgestrel) or a 30 ug (+ 150ug d-norgestrel) containing oral contraceptive. In addition, single plasma EE determinations were performed in 110 chronic oral contraceptive users. Whereas different patterns in plasma EE levels (sampling 24 hours following last pill ingestion) were observed among the different volunteers, the mean levels increased progressively during treatment and reflected closely the differences in dosage. The values obtained in the volunteers at the end of the treatment cycle showed important interindividual variations. The findings during a first treatment cycle or during the following ones were similar and for different treatment cycles in the same patient, the patterns in plasma EE levels were consistent. The results for single plasma determinations in chronic contraceptive users (sampling between 8th and 21st day of treatment cycle, 9 to 24 hours since last pill ingestion) showed more pronounced interindividual variations, the individual EE levels being not correlated to parameters such as body weight, body surface, months of oral contraception prior to the study, sex hormone binding capacity or day of the cycle. However, significant differences in mean plasma EE levels were noticed for patients treated with different commercial preparations with identical EE content, suggesting the existence of differences in bioavailability. The relevancy of plasma EE determinations is discussed and from the results of the present study, it is concluded that a strictly standardized time of sampling is an absolute condition for obtaining interpretable results.