Gestodene and desogestrel do not have a different influence on concentration profiles of ethinylestradiol in women taking oral contraceptives--results of isotope dilution mass spectrometry measurements.
OBJECTIVE
A new method for the quantitative determination of 17alpha-ethinylestradiol-17beta (EE2) in serum is presented here based on the principle of isotope dilution mass spectrometry (IDMS) with [13C]EE2 as internal standard. The technique was used to determine the concentration profiles of EE2 in the serum of female subjects who had taken oral contraceptives with different progestin components. The method has proved to be very reliable with respect to trueness, specificity, precision and detection sensitivity and offers considerable advantages compared with the immunological methods of measurement used to date.


METHODS
Forty-seven female volunteers took two different oral contraceptives containing EE2 combined with different progestins in accordance with a cross-over design. After the administration of 30 microg EE2 combined with 75 microg gestodene (EE2/GSD) or 150 microg desogestrel (EE2/DES), blood samples were taken from the subjects on certain days and in certain previously specified cycles in the course of 12 h after medication.


CONCLUSIONS
The biometric analysis of the results showed that the concentration profiles of EE2 were in their statistics, significantly equivalent after the administration of either of the two oral contraceptives. The sometimes contradictory results found in former studies after the administration of the different contraceptives were presumably due to the methodological shortcomings of the radioimmunological measurement technique. With the use of the highly accurate and specific technique of IDMS it can now be unequivocally established that the different progestins in the tested oral contraceptives have no influence on the bioavailability of EE2 (area under EE2 serum concentration curves, as usually defined in pharmacokinetics).
Siekmann
L
L
Institut für Klinische Biochemie, Universität Bonn, Germany.
Siekmann
A
A
Bidlingmaier
F
F
Brill
K
K
Albring
M
M
D000284:Administration, Oral; D019540:Area Under Curve; D001682:Biological Availability; D002247:Carbon Isotopes; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage*; D018592:Cross-Over Studies; D017135:Desogestrel / Q000008:administration & dosage*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000097:blood*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D008597:Menstrual Cycle / Q000187:drug effects; D009543:Nifedipine / Q000493:pharmacokinetics; D009652:Norpregnenes / Q000008:administration & dosage*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D002247:Carbon Isotopes; D003277:Contraceptives, Oral, Combined; D009652:Norpregnenes; C033273:Gestodene; D004997:Ethinyl Estradiol; D017135:Desogestrel; D009543:Nifedipine