The bioequivalence of the contraceptive steroids ethinylestradiol and drospirenone is not affected by co-administration of dehydroepiandrosterone

ABSTRACT

Objectives To study the effect of co-administration of 50 mg dehydroepiandrosterone (DHEA) on the bioequivalence of ethinylestradiol (EE) and drospirenone (DRSP) in women who were using a combined oral contraceptive (COC) containing 30 μg EE and 3 mg DRSP, and to estimate whether the addition of DHEA to this COC affects the serum levels and the bioequivalence of the synthetic contraceptive steroids.

Methods This was a randomised, double-blind, two-period crossover study. Participants received two EE/DRSP COC treatment cycles in random order, one with and one without daily 50 mg DHEA , separated by a 28-day wash-out cycle during which the subjects used an EE/levonorgestrel (LNG) COC without DHEA. Serum levels of EE and DRSP were measured according to a sampling scheme allowing pharmacokinetic evaluations.

Results Addition of DHEA to an EE/DRSP COC had no effect on serum levels of EE and DRSP. The COC regimens with and without DHEA were bioequivalent. Oestradiol levels were equally suppressed during pill intake, whether with placebo or DHEA.

Conclusion Adding DHEA to a COC containing EE and DRSP does not affect the pharmacokinetic properties of EE and DRSP. Therefore, it will most likely not affect its contraceptive efficacy.

Keywords:

• Oral contraception
• DHEA administration
• Bioequivalence
• Ethinylestradiol
• Drospirenone

ACKNOWLEDGEMENTS

We acknowledge the excellent contribution of Frieda Ebes and Louise Beekman in the preparation and conduct of the study. We would also like to thank Prof. Dr B. C. J. M. Fauser for his review of the manuscript.

Declaration of interest: All three authors have a potential conflict of interest due to their relationship with the company Pantarhei Bioscience (PRB), developing the ARC concept for contraception. Yvette Zimmerman is an employee of PRB, Wout Wouters is a paid consultant of PRB, and Herjan Coelingh Bennink is the CEO and a shareholder of PRB. The authors have done their utmost to avoid being influenced. After publication of the paper, PRB will make the clinical study report available upon request. The authors alone are responsible for the content and the writing of the paper.

Source of funding: The study was financed by Pantarhei Bioscience.