Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive

Abstract

Introduction: The objective of this open-label randomized study was to directly compare the pharmacokinetics of ethinylestradiol (EE) released from three hormonal contraceptive methods that use different routes of administration. Such a three-way pharmacokinetic comparison has not been previously reported; the goal of this study was to gain insight into EE exposure with these contraceptive formulations.Materials and Methods: After 2���8 weeks of synchronization by combined oral contraceptive (COC) treatment, subjects were randomized to 21 days of treatment with the contraceptive vaginal ring, NuvaRing��, the transdermal patch or a COC containing 30-��g EE (Levlen��/Microgynon��).Results: Analysis of the area under the EE concentration���time curve during the 21-day treatment showed the following pattern of results: exposure to EE was lowest in the NuvaRing�� group (15-��g EE/day), followed by that in the COC group (30-��g EE/day; p<.05), and was highest in the patch group (20-��g EE/day; p<.05). Exposure to EE in the NuvaRing�� group was 3.4 times lower than that in the patch group and 2.1 times lower than that in the COC group. In addition, subjects' serum EE levels showed much lower variations with NuvaRing�� than with either the patch or the COC.Conclusion: This study demonstrates that EE exposure in women using combined contraception is significantly affected not only by the daily dosage of EE, which was to be expected, but also by the route of administration of the contraceptive method. Introduction: The objective of this open-label randomized study was to directly compare the pharmacokinetics of ethinylestradiol (EE) released from three hormonal contraceptive methods that use different routes of administration. Such a three-way pharmacokinetic comparison has not been previously reported; the goal of this study was to gain insight into EE exposure with these contraceptive formulations. Materials and Methods: After 2���8 weeks of synchronization by combined oral contraceptive (COC) treatment, subjects were randomized to 21 days of treatment with the contraceptive vaginal ring, NuvaRing��, the transdermal patch or a COC containing 30-��g EE (Levlen��/Microgynon��). Results: Analysis of the area under the EE concentration���time curve during the 21-day treatment showed the following pattern of results: exposure to EE was lowest in the NuvaRing�� group (15-��g EE/day), followed by that in the COC group (30-��g EE/day; p<.05), and was highest in the patch group (20-��g EE/day; p<.05). Exposure to EE in the NuvaRing�� group was 3.4 times lower than that in the patch group and 2.1 times lower than that in the COC group. In addition, subjects' serum EE levels showed much lower variations with NuvaRing�� than with either the patch or the COC. Conclusion: This study demonstrates that EE exposure in women using combined contraception is significantly affected not only by the daily dosage of EE, which was to be expected, but also by the route of administration of the contraceptive method.