Chronic Antiprogestin Therapy Produces a Stable Atrophic Endometrium With Decreased Fibroblast Growth Factor: A 1-Year Primate Study on Contraception and Amenorrhea

Daniel R. Grow, M T Reece, Jeng G. Hsiu, L A Adams, Patricia M. Newcomb, Robert F. Williams, Gary D. Hodgen
In: Fertility and Sterility · 1998 · vol. 69(5) , pp. 936–943 · doi:10.1016/s0015-0282(98)00029-6 · PMID:9591506 · W2061581560
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This 1-year primate study found that chronic antiprogestin therapy induces a stable atrophic endometrium, characterized by reduced fibroblast growth factor levels, offering potential insights into contraception and amenorrhea.

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Abstract

ObjectiveTo describe the efficacy of mifepristone in the prevention of menstrual bleeding and ovulation, with similar observations in comparison groups.DesignProspective experimental study. Thirty-two cynomolgus 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 mifepristone only, group III received GnRH-a only, and group IV received vehicle control.Main outcome measure(s)Serum estradiol and progesterone, menstrual bleeding, endometrial thickness, and endometrial expression of basic fibroblast growth factor (bFGF) as determined by immunohistochemistry.Result(s)Weekly progesterone determinations showed that mifepristone-treated monkeys seldom ovulated (6 ovulations in 8 years), compared with the controls (100 ovulations in 8 years), while maintaining early to midfollicular levels of circulating serum estradiol. The GnRH-a-only group also rarely ovulated, but was chronically and severely hypoestrogenic. The mifepristone-only group showed scant menstrual bleeding (5 days in 8 years) as compared with the menstrual frequency in control animals (422 days in 8 years). Endometrial proliferation, as determined by biopsy, was similarly minimal for both the GnRH-a and mifepristone groups, and statistically less than in control monkeys. 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.

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