, Volume 14, Issue 1, pp 109–117 | Cite as

The influence of combined oral contraceptives containing drospirenone on hypothalamic-pituitary-adrenocortical axis activity and glucocorticoid receptor expression and function in women with polycystic ovary syndrome

  • Djuro Macut
  • Ivana Božić Antić
  • Jelena Nestorov
  • Vladanka Topalović
  • Jelica Bjekić Macut
  • Dimitrios Panidis
  • Biljana Kastratović Kotlica
  • Efstathios Papadakis
  • Gordana Matić
  • Danijela Vojnović MilutinovićEmail author
Research paper


OBJECTIVE: Most women with PCOS have increased adrenal androgen production, enhanced peripheral metabolism of Cortisol and elevation in urinary excretion of its metabolites. Increased Cortisol clearance in PCOS is followed by a compensatory overdrive of the hypothalamic-pituitary-adrenocortical (HPA) axis. We hypothesized that oral contraceptives containing ethinylestradiol and drospirenone (EE-DRSP) could modulate glucocorticoid receptor (GR) expression and function and thus affect HPA axis activity in PCOS patients. DESIGN: We analyzed 12 women with PCOS (age 24.17±4.88 years; body mass index 22.05±3.97 kg/m2) treated for 12 months with EE-DRSP and 20 BMI-matched controls. In all subjects testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), Cortisol (basal and after dexamethasone), concentrations of GR protein, phospo-GR211 protein, number of GR per cell (Bmax) and its equilibrium dissociation constant (KD) were measured. RESULTS: Before treatment, increased concentrations of testosterone and DHEAS (p<0.001, respectively), unaltered basal Cortisol and an increased sensitivity (p<0.05) of the HPA axis to dexamethasone were observed in PCOS women in comparison to controls. After treatment, testosterone (p<0.01), DHEAS (p<0.05) and Cortisol suppression after dexamethasone (p<0.01) were decreased in PCOS women. There were no changes in GR protein concentration, GR phosphorylation nor in the receptor functional parameters Bmax and KD in women with PCOS before and after the therapy, and in comparison to controls. CONCLUSIONS: Prolonged treatment with EE-DRSP in PCOS women decreased serum androgens and increased Cortisol in the presence of decreased sensitivity of the HPA axis and did not exert changes in GR expression and function.

Key terms

Combined oral contraceptives Cortisol Drospirenone Glucocorticoid receptor HPA axis Polycystic ovary syndrome 


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Copyright information

© Hellenic Endocrine Society 2015

Authors and Affiliations

  • Djuro Macut
    • 1
  • Ivana Božić Antić
    • 1
  • Jelena Nestorov
    • 2
  • Vladanka Topalović
    • 2
  • Jelica Bjekić Macut
    • 3
  • Dimitrios Panidis
    • 4
  • Biljana Kastratović Kotlica
    • 5
  • Efstathios Papadakis
    • 4
  • Gordana Matić
    • 2
  • Danijela Vojnović Milutinović
    • 2
    Email author
  1. 1.Institute of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia and School of MedicineUniversity of BelgradeBelgradeSerbia
  2. 2.Department of Biochemistry, Institute for Biological Research “Siniša Stanković”University of BelgradeBelgradeSerbia
  3. 3.CHC Bežanijska kosaBelgradeSerbia
  4. 4.Division of Endocrinology and Human Reproduction, 2nd Department of Obstetrics and GynecologyAristotle University of ThessalonikiThessalonikiGreece
  5. 5.Clinic of Obstetrics and Gynecology, Faculty of MedicineUniversity of BelgradeBelgradeSerbia

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