The effect of a continuous regimen of drospirenone 3 mg/ethinylestradiol 30 microg on Cox-2 and Ki-67 expression in the endometrium

Eur J Contracept Reprod Health Care. 2010 Feb;15(1):35-40. doi: 10.3109/13625180903383928.

Abstract

Objective: To study Cox-2 expression in relation to bleeding patterns in patients using an oral contraceptive containing 3 mg of drospirenone and 30 microg of ethinylestradiol (DRSP/EE).

Methods: Forty-three patients of reproductive age with symptoms of menorrhagia and dysmenorrhoea, who were submitted to endometrial resection, were enrolled. Twelve patients were in the proliferative phase and the remaining 31 were either currently using DRSP/EE or had discontinued its use four to eight days prior to hysteroscopy. Cox-2 and Ki-67 expression were determined in the endometrium using immunohistochemistry.

Results: Cox-2 expression was significantly inhibited in the glandular epithelium of patients who became amenorrhoeic during DRSP/EE use; however, in patients with breakthrough bleeding and in those who had stopped oral contraceptive use, a significant increase occurred in Cox-2 expression in the endometrium. Ki-67 expression decreased significantly during DRSP/EE use, but returned to proliferative phase values four to eight days after discontinuation of treatment.

Conclusion: These results suggest that endometrial bleeding during DRSP/EE use is associated with an increase in Cox-2 expression in the endometrium. A similar increase was also seen four to eight days following discontinuation of the oral contraceptive.

MeSH terms

  • Adult
  • Androstenes / administration & dosage
  • Androstenes / pharmacology*
  • Contraceptives, Oral, Synthetic / administration & dosage
  • Contraceptives, Oral, Synthetic / pharmacology*
  • Cyclooxygenase 2 / metabolism*
  • Dose-Response Relationship, Drug
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Endometrium / pathology
  • Estrogens / administration & dosage
  • Estrogens / pharmacology*
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / pharmacology*
  • Female
  • Humans
  • Ki-67 Antigen / metabolism*
  • Mineralocorticoid Receptor Antagonists / administration & dosage
  • Mineralocorticoid Receptor Antagonists / pharmacology*
  • Observation
  • Uterine Hemorrhage / drug therapy

Substances

  • Androstenes
  • Contraceptives, Oral, Synthetic
  • Estrogens
  • Ki-67 Antigen
  • Mineralocorticoid Receptor Antagonists
  • Ethinyl Estradiol
  • Cyclooxygenase 2
  • drospirenone