Pharmacokinetics and pharmacodynamics of oral contraceptive steroids: factors influencing steroid metabolism.
The time-dependent alterations in the serum concentrations of ethinyl estradiol, gestodene, and 3-keto-desogestrel during treatment with 30 micrograms of ethinyl estradiol + 75 micrograms of gestodene or 30 micrograms of ethinyl estradiol + 150 micrograms of desogestrel were investigated during 12 months. The levels of gestodene and 3-keto-desogestrel increased between days 1 and 21 of each cycle, reaching maximal levels during the third and sixth cycles. The serum concentrations of gestodene were fourfold to fivefold higher than those of 3-keto-desogestrel. The ethinyl estradiol levels increased significantly between days 1 and 10 during each cycle and were significantly higher by 70% during intake of ethinyl estradiol/gestodene compared with ethinyl estradiol/desogestrel, although the dose was identical. Intake of gestodene, in addition to 35 micrograms of ethinyl estradiol + 2 mg of cyproterone acetate, caused a rise in ethinyl estradiol levels. During treatment with ethinyl estradiol/gestodene and an additional 150 micrograms of levonorgestrel, there was a continuous increase in gestodene levels, although sex hormone-binding globulin level did not change. During treatment with 30 or 35 micrograms of ethinyl estradiol and 75 micrograms of gestodene, 150 micrograms of desogestrel, or 2 mg of cyproterone acetate, there were large intraindividual and interindividual variations in the steroid levels and ratios of estrogen: progestogen levels. There was no correlation with the occurrence of intermenstrual bleedings. It is concluded that ethinyl estradiol and nortestosterone derivatives may inhibit steroid-metabolizing enzymes in the liver, which results in a rise in the serum levels of contraceptive steroids. The cause of the large intraindividual variations is as yet unknown, but it is probably from changes in steroid metabolism.
Jung-Hoffman
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Department of Obstetrics and Gynecology, J. W. Goethe University, Frankfurt, Federal Republic of Germany.
Kuhl
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D000293:Adolescent; D000328:Adult; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003534:Cyproterone / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D017373:Cyproterone Acetate; D017135:Desogestrel; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007700:Kinetics; D016912:Levonorgestrel; D008597:Menstrual Cycle / Q000097:blood; D009644:Norgestrel / Q000493:pharmacokinetics; D009652:Norpregnenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
D003278:Contraceptives, Oral, Hormonal; D009652:Norpregnenes; D012738:Sex Hormone-Binding Globulin; C033273:Gestodene; C044815:etonogestrel; D009644:Norgestrel; D004997:Ethinyl Estradiol; D017373:Cyproterone Acetate; D016912:Levonorgestrel; D017135:Desogestrel; D003534:Cyproterone