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. Design: A prospective, randomized, placebo-controlled trial. Setting: Reproductive research center. Patient(s): Fifty healthy women with regular menstrual cycle. Intervention(s): 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. Main Outcome Measure(s): The expression of estrogen receptor sub-types alpha and- beta (ER alpha and ER beta), progesterone receptors A and B (PRAB and, PRB), and androgen receptor messenger RNA and protein was, detected by real-time polymerase chain reaction and. immumohistochemist, respectively. Steroid receptor coactivator proliferation (SRC-1), silencing mediator for retinoid and thyroid-1 hormone receptors, and cell proliferation were evaluated by immumohistochemistry. Result(s): The expression of endometrial ER alpha, PRAB, PRB and SRC-1 wa increaseds significantly after 1 week of mifepristone, but the increase was no longer seen after 10 weeks. A positive correlation between endometrial ER alpha PRAB, PRB, and SRC-1 production and proliferation was demonstrated. Conclusion(s): Short-term exposure of mifepristone in new starters of, DMPA increases the expression of, endometrial ER alpha, PRAB, PRB, and SRC-1 and promotes cell proliferation. Prolonged exposure to,mifepristone does not alter the suppression of these receptors that are ca sed by DMPA and continuea to result in endometrial atrophy.