Endometrial effects of a single early luteal dose of the selective progesterone receptor modulator CDB-2914

Fertil Steril. 2010 Apr;93(6):2035-41. doi: 10.1016/j.fertnstert.2008.12.057. Epub 2009 Feb 6.

Abstract

Objective: To test potential contraceptive mechanisms of the selective P receptor modulator CDB-2914 in the early luteal phase.

Design: Prospective randomized clinical trial.

Setting: Clinical research center.

Patient(s): Fifty-six women with regular cycles.

Intervention(s): Women received a single dose of CDB-2914 (10, 50, or 100 mg) or placebo given after ovulation and within 2 days of the LH surge. Four to 6 days later, a transvaginal ultrasound scan measured endometrial thickness, and an endometrial biopsy specimen was obtained.

Main outcome measure(s): The endometrium was evaluated by thickness and by immunohistochemical analysis for P-dependent markers; safety laboratory tests were performed, and E(2) and P levels were obtained.

Result(s): CDB-2914 caused a significant dose-dependent decrease in endometrial thickness, an increase in glandular P receptors, and a decrease in peripheral node addressins. Estradiol and P levels and menstrual cycle timing were not altered. No adverse effects were observed.

Conclusion(s): The alteration in endometrial thickness and P-dependent markers of implantation in the absence of changes in hormone levels and cycle length suggests that CDB-2914 may have contraceptive properties.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Dose-Response Relationship, Drug
  • Endometrium / anatomy & histology
  • Endometrium / diagnostic imaging
  • Endometrium / drug effects*
  • Endometrium / physiology
  • Female
  • Gonadal Steroid Hormones / blood
  • Hormone Antagonists / administration & dosage
  • Hormone Antagonists / adverse effects
  • Humans
  • Luteal Phase / blood
  • Luteal Phase / drug effects*
  • Luteal Phase / physiology
  • Norpregnadienes / administration & dosage*
  • Norpregnadienes / adverse effects
  • Organ Size / drug effects
  • Placebos
  • Progesterone Congeners / administration & dosage
  • Progesterone Congeners / adverse effects
  • Receptors, Progesterone / antagonists & inhibitors*
  • Receptors, Progesterone / metabolism
  • Substrate Specificity
  • Time Factors
  • Ultrasonography
  • Young Adult

Substances

  • Gonadal Steroid Hormones
  • Hormone Antagonists
  • Norpregnadienes
  • Placebos
  • Progesterone Congeners
  • Receptors, Progesterone
  • ulipristal