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 comparison groups.


METHODS
Prospective experimental study. Thirty-two cynomolgus monkeys were divided equally into four treatment groups (n = 8). Treatment lasted for 1 year.


METHODS
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.


METHODS
Serum estradiol and progesterone, menstrual bleeding, endometrial thickness, and endometrial expression of basic fibroblast growth factor (bFGF) as determined by immunohistochemistry.


RESULTS
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.


CONCLUSIONS
Chronic mifepristone induced anovulation along with virtual amenorrhea, which suggests the worth of this novel hormonal contraceptive.
Grow
D R
DR
Department of Obstetrics and Gynecology, Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts 01199, USA.
Reece
M T
MT
Hsiu
J G
JG
Adams
L
L
Newcomb
P M
PM
Williams
R F
RF
Hodgen
G D
GD
D000568:Amenorrhea / Q000139:chemically induced*; D000818:Animals; D003267:Contraception; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis*; D006727:Hormone Antagonists / Q000494:pharmacology*; D016729:Leuprolide / Q000494:pharmacology; D008252:Macaca fascicularis; D015735:Mifepristone / Q000494:pharmacology*; D010060:Ovulation / Q000187:drug effects
D006727:Hormone Antagonists; D016222:Fibroblast Growth Factor 2; D015735:Mifepristone; D016729:Leuprolide