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.
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.


METHODS
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 (B(max) and its equilibrium dissociation constant (K(D)) 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 B(max) and K(D) 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.
Djuro
D
Macut
Ivana
I
Božić Antić
Jelena
J
Nestorov
Vladanka
V
Topalović
Jelica
J
Bjekić Macut
Dimitrios
D
Panidis
Biljana
B
Kastratović Kotlica
Efstathios
E
Papadakis
Gordana
G
Matić
Danijela
D
Vojnović Milutinović
D000328:Adult; D000736:Androstenes / Q000494:pharmacology*; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011085:Polycystic Ovary Syndrome / Q000378:metabolism / Q000503:physiopathology*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D055815:Young Adult
D000736:Androstenes; D003277:Contraceptives, Oral, Combined; D000451:Mineralocorticoid Receptor Antagonists; D011965:Receptors, Glucocorticoid; D012738:Sex Hormone-Binding Globulin; C534342:drospirenone and ethinyl estradiol combination; D013739:Testosterone; D004997:Ethinyl Estradiol; D019314:Dehydroepiandrosterone Sulfate; D006854:Hydrocortisone