Interruption of endometrial maturation without hormonal changes by an antiprogesterone during the first half of luteal phase of the menstrual cycle: a contraceptive potential

Abstract

Objective: To examine hormonal and endometrial responses to intermittent low-dose RU486 administration in the luteal phase of the menstrual cycle.

Design: Prospective open trial in which subjects serve as their own controls.

Patients/participants: Eight normal cycling women.

Interventions: RU486 (10 mg, orally) was administered 5 and 8 days after urinary luteinizing hormone (LH) surge of treatment cycle.

Main outcome measures: Daily serum concentrations of LH, follicle-stimulating hormone, estradiol (E2), and progesterone (P) were determined in control, treatment, and recovery cycles (n = 5) or treatment and recovery cycles (n = 3). Changes in endometrial morphology and immunohistochemical staining for P receptor (PR) and E2 receptor (ER) were determined during control (or recovery) and treatment cycles.

Results: Cycle length and hormonal patterns were unaltered after treatment with RU486. As demonstrated by reduced stromal edema and delayed glandular development, endometrial dyssynchrony occurred in all eight treatment cycles. In addition, seven of eight treatment cycle endometria demonstrated a decrease in PR staining without consistent change in ER staining.

Conclusions: Two low doses of RU486 given 72 hours apart during the luteal phase of the cycle disrupted ongoing endometrial maturation without altering the hormonal and time course of the menstrual cycle. This study provides a basis for the development of a novel form of luteal contraception.

PIP: This study sought to examine hormonal and endometrial responses to intermittent low-dose RU486 administration in the luteal phase of the menstrual cycle. 8 normally cycling women participated in this prospective open trail in which the subjects served as their own controls. RU486 (10 mg, orally) was administered 5 and 8 days after urinary luteinizing hormone (LH) surge of treatment cycle. Daily serum concentrations of LH, follicle stimulating hormone, estradiol (E2), and progesterone (P) were determined in control, treatment, and recovery cycles (n=5) or treatment and recovery cycles (n=3). Changes in endometrial morphology and immunohistochemical staining for P receptor (PR) and E2 receptor (ER) were determined during control (or recovery) and treatment cycles. Cycle length and hormonal patterns were unaltered after treatment with RU486. As demonstrated by reduced stromal edema and delayed glandular development, endometrial dyssynchrony occurred in all 8 treatment cycles. In addition, 7 of 8 treatment cycle endometria demonstrated a decrease in PR staining without consistent change in Er staining. The authors conclude that 2 low doses of RU486 given 72 hours apart during the luteal phase of the cycle disrupt ongoing endometrial maturation without altering the hormonal and time course of the menstrual cycle. This study provides a basis for the development of a novel form of luteal contraception.