Effects of mifepristone on proliferation and apoptosis of human endometrium in new users of medroxyprogesterone acetate.
BACKGROUND
Mifepristone has been demonstrated to decrease breakthrough bleeding (BTB) in users of progestin-only contraceptives.


METHODS
Endometrial biopsies were collected from 50 normal cycling women who were new users of depot medroxyprogesterone acetate (DMPA) randomized to receive either mifepristone or placebo before, during and after treatment. Proliferation, apoptosis and sex steroid receptors were evaluated by either immunohistochemistry or TUNEL assay.


RESULTS
Administration of mifepristone to DMPA-exposed endometrium for 1 week significantly increased endometrial expression of Ki-67 (MKI67), estrogen receptor (ER)alpha and progesterone receptors A and B (PRAB) and decreased the number of TUNEL-positive and caspase-3 (CASP3)-active cells in the endometrial stroma. However, after 10 weeks of mifepristone treatment, no significant difference in proliferation, apoptosis and the expression of ERalpha or PRAB could be detected between the endometrium treated with DMPA alone and endometrium treated with mifepristone and DMPA.


CONCLUSIONS
Administration of mifepristone to DMPA users significantly increases endometrial proliferation and decreases endometrial stromal apoptosis in the short term. Prolonged exposure to mifepristone does not counteract the inhibitory effects of progestin therapy on endometrial proliferation. Estrogen and progesterone receptors may play an important role in these effects.
Jain
John K
JK
Department of Obstetrics and Gynecology, The Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. jjain@usc.edu
Li
Aimin
A
Yang
Wangrong
W
Minoo
Parviz
P
Felix
Juan C
JC
D000814:Aniline Compounds / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003271:Contraceptive Agents, Female / Q000494:pharmacology*; D004311:Double-Blind Method; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*
D000814:Aniline Compounds; D003271:Contraceptive Agents, Female; C050795:N,N-dimethyl-4-anisidine; D017258:Medroxyprogesterone Acetate