CHRONIC ANTIPROGESTIN THERAPY PRODUCES A STABLE ATROPHIC ENDOMETRIUM WITH DECREASED FIBROBLAST GROWTH-FACTOR - A 1-YEAR PRIMATE STUDY ON CONTRACEPTION AND AMENORRHEA

Objective: To describe the efficacy of mifepristone in the prevention of menstrual bleeding and ovulation, with similar observations in comp arison groups. Design: Prospective experimental study. Thirty-two cyno molgus monkeys were divided equally into four treatment groups (n = 8) . Treatment lasted for 1 year. Intervention(s): Group I received GnRH- agonist (GnRH-a) and in-sequence mifepristone, group II received mifep ristone only, group III received GnRH-a only, and group TV received ve hicle control. Main Outcome Measure(s): Serum estradiol and progestero ne, menstrual bleeding, endometrial thickness, and endometrial express ion of basic fibroblast growth factor (bFGF) as determined by immunohi stochemistry. Result(s): Weekly progesterone determinations showed tha t mifepristone-treated monkeys seldom ovulated (6 ovulations in 8 year s), compared with the controls (100 ovulations in 8 years), while main taining early to midfollicular levels of circulating serum estradiol. The GnRH-a-only group also rarely ovulated, but was chronically and se verely hypoestrogenic. The mifepristone-only group showed scant menstr ual bleeding (5 days in 8 years) as compared with the menstrual freque ncy in control animals (422 days in 8 years). Endometrial proliferatio n, as determined by biopsy, was similarly minimal for both the GnRH-a and mifepristone groups, and statistically less than in control monkey s. Both the mifepristone and GnRH-a treatments suppressed endometrial gland expression of the angiogenesis polypeptide bFGF. Conclusion(s): Chronic mifepristone induced anovulation along with virtual amenorrhea , which suggests the worth of this novel hormonal contraceptive, (C) 1 998 by American Society for Reproductive Medicine.