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


CONCLUSIONS
By adding DHEA to a COC the loss of adrenal and ovarian androgens can be restored.
* Pantarhei Bioscience , Zeist , the Netherlands.
Yvette
Y
Zimmerman
Herjan J T
HJ
Coelingh Bennink
Wout
W
Wouters
Frieda
F
Ebes
Bart C J M
BC
Fauser
D000328:Adult; D000704:Analysis of Variance; D000736:Androstenes / Q000494:pharmacology*; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000097:blood / Q000493:pharmacokinetics*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000494:pharmacology*; D011247:Pregnancy; D011446:Prospective Studies; D013739:Testosterone / Q000097:blood*
D000736:Androstenes; D003277:Contraceptives, Oral, Combined; D013739:Testosterone; D004997:Ethinyl Estradiol; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D016912:Levonorgestrel; C035144:drospirenone