Pharmacokinetics and pharmacodynamics of oral contraceptive steroids: factors influencing steroid metabolism

Am J Obstet Gynecol. 1990 Dec;163(6 Pt 2):2183-97. doi: 10.1016/0002-9378(90)90560-t.


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.

MeSH terms

  • Adolescent
  • Adult
  • Contraceptives, Oral, Hormonal / administration & dosage
  • Contraceptives, Oral, Hormonal / blood
  • Contraceptives, Oral, Hormonal / pharmacokinetics*
  • Cyproterone / analogs & derivatives
  • Cyproterone / pharmacokinetics
  • Cyproterone Acetate
  • Desogestrel
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / blood
  • Ethinyl Estradiol / pharmacokinetics
  • Female
  • Humans
  • Kinetics
  • Levonorgestrel
  • Menstrual Cycle / blood
  • Norgestrel / pharmacokinetics
  • Norpregnenes / administration & dosage
  • Norpregnenes / blood
  • Norpregnenes / pharmacokinetics
  • Sex Hormone-Binding Globulin / metabolism


  • Contraceptives, Oral, Hormonal
  • Norpregnenes
  • Sex Hormone-Binding Globulin
  • Gestodene
  • etonogestrel
  • Norgestrel
  • Ethinyl Estradiol
  • Cyproterone Acetate
  • Levonorgestrel
  • Desogestrel
  • Cyproterone