Mifepristone alters expression of endometrial steroid receptors and their cofactors in new users of medroxyprogesterone acetate.
OBJECTIVE
To evaluate the effect of mifepristone on the expression of endometrial steroid receptors and their co-factors in depot medroxyprogesterone acetate (DMPA) users.


METHODS
A prospective, randomized, placebo-controlled trial.


METHODS
Reproductive research center.


METHODS
Fifty healthy women with regular menstrual cycle.


METHODS
One hundred fifty milligrams of DMPA were given every 3 months. Two pills (25 mg each) of placebo or mifepristone were administered every 14 days during the DMPA therapy. Four endometrial biopsy specimens were obtained from each patient.


METHODS
The expression of estrogen receptor subtypes alpha and beta (ERalpha and ERbeta), progesterone receptors A and B (PRAB and PRB), and androgen receptor messenger RNA and protein was detected by real-time polymerase chain reaction and immunohistochemistry, respectively. Steroid receptor coactivator 1 (SRC-1), silencing mediator for retinoid and thyroid-hormone receptors, and cell proliferation were evaluated by immunohistochemistry.


RESULTS
The expression of endometrial ERalpha, PRAB, PRB, and SRC-1 was increased significantly after 1 week of mifepristone, but the increase was no longer seen after 10 weeks. A positive correlation between endometrial ERalpha, PRAB, PRB, and SRC-1 production and proliferation was demonstrated.


CONCLUSIONS
Short-term exposure of mifepristone in new starters of DMPA increases the expression of endometrial ERalpha, PRAB, PRB, and SRC-1 and promotes cell proliferation. Prolonged exposure to mifepristone does not alter the suppression of these receptors that are caused by DMPA and continues to result in endometrial atrophy.
Jain
John K
JK
Department of Obstetrics and Gynecology, The Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. jjain@usc.edu
Li
Aimin
A
Yang
Wangrong
W
Minoo
Parviz
P
Felix
Juan C
JC
D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage; D004311:Double-Blind Method; D004338:Drug Combinations; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D015735:Mifepristone / Q000008:administration & dosage*; D015990:Placebo Effect; D020033:Protein Isoforms / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*
D003280:Contraceptives, Oral, Synthetic; D004338:Drug Combinations; D020033:Protein Isoforms; D011987:Receptors, Steroid; D015735:Mifepristone; D017258:Medroxyprogesterone Acetate