The pharmacokinetics and pharmacodynamics of dehydroepiandrosterone during use of an ethinylestradiol- and drospirenone-containing oral contraceptive

Abstract

Background Combined oral contraceptives (COCs) reduce the levels of ovarian and adrenal androgens. Co-administration of dehydroepiandrosterone (DHEA) may normalise androgen levels during COC use.

Objective To investigate the effect of the addition of DHEA to a COC on the pharmacokinetics (PK) and pharmacodynamics (PD) of DHEA and its sulphate (DHEA-S), and on levels of total and free testosterone (T).

Methods In a prospective, randomised, double-blind, placebo-controlled, cross-over study involving 21 female volunteers, the PK and PD of DHEA and DHEA-S were investigated during the use of one cycle of a COC containing 30 μg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) with and without daily co-administration of 50 mg DHEA.

Results Treatment during one cycle with a COC containing EE and DRSP reduces the exposure to DHEA and DHEA-S by at least 20%. This loss of adrenal androgens can be fully compensated by daily oral co-administration of 50 mg DHEA. With DHEA co-administration total T levels rise significantly (1.44 nmol/L with DHEA vs. 0.82 nmol/L with placebo; p < 0.001). Free T levels decrease significantly with both DHEA and placebo treatment, but significantly less during co-administration of DHEA (6.34 pmol/L with DHEA vs. 3.96 pmol/L with placebo; p < 0.001).

Conclusion By adding DHEA to a COC the loss of adrenal and ovarian androgens can be restored.

Keywords:

• Oral contraception
• Androgens
• DHEA
• DHEA-S
• Testosterone
• Pharmacokinetics

ACKNOWLEDGEMENTS

We acknowledge the excellent contribution of Louise Beekman in the monitoring of the study.

Declaration of interest: Yvette Zimmerman and Wout Wouters are employed by Pantarhei Bioscience (PRB) developing the ARC concept for contraception. Herjan Coelingh Bennink is CEO of PRB and has equity interests in the company. Frieda Ebes reports no conflict of interest. Bart Fauser has received fees and grant support from the following companies (in alphabetical order): Andromed, Ardana, Auxogyn, Ferring, Genovum, Merck (MSD), Merck Serono, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono, Uteron Pharma, Watson Pharmaceuticals and Wyeth.

After publication of the paper, PRB will make the clinical study report available upon request.

The study was financially supported by Pantarhei Bioscience.