Alterations in the serum levels of gestodene and SHBG during 12 cycles of treatment with 30 micrograms ethinylestradiol and 75 micrograms gestodene.

The serum concentrations of gestodene have been measured radioimmunologically in 11 female volunteers on Day 1, 10, and 21 of the 1st, 3rd, 6th, and 12th cycle of treatment with an oral contraceptive containing 30 micrograms ethinylestradiol and 75 micrograms gestodene during the first 4 hours and 24 hours after intake. During the 1st cycle the maximal gestodene levels increased from 2.1 to 6.2 ng/ml on Day 1 to values between 7.5 and 22.0 ng/ml on Day 21. During the 3rd and 6th treatment cycle the levels were still higher with maxima between 10.1 and 26.3 ng/ml, while during the 12th cycle the gestodene concentrations were slightly lower. The serum levels of SHBG rose significantly during intake of the pill up to values between 210 and 240 nmol/l on Day 21 of each cycle, and were reduced to a certain degree during the pill-free interval. The SHBG concentrations correlated closely with the area under the gestodene concentration-versus-time curves (AUC) indicating a pronounced influence of serum protein binding upon the pharmacokinetics of gestodene. The gestodene levels of the individual women remained relatively constant during the 12 treatment cycles, although great interindividual differences were found. It is concluded that the relatively high serum concentrations of gestodene are not only based on the binding to SHBG, but probably also on an impeded metabolism of gestodene.