Long-term mifepristone (RU486) therapy resulting in massive benign endometrial hyperplasia

Mifepristone (RU486) is a potent antiprogestagen, and at high doses it also acts as an antiglucocorticoid drug. Mifepristone, administered as a single 600 mg dose, is commonly employed to induce medical abortion in conjunctio n with prostaglandins. The long-term safety profile of mifepristone, especi ally at high doses, is less well-established. Long-term mifepristone is con sidered efficacious in treating uterine myomas, endometriosis (25-100 mg/da y), and possibly in inoperable meningiomas (200 mg/day), as well as inopera ble Cushing's syndrome. Many animal studies document an antiproliferative e ffect (antioestrogenic), as do some reports in humans. However, there are a lso data to suggest that, as an antiprogestagen, mifepristone may promote a n unopposed oestrogen milieu, and thus have a proliferative effect upon the endometrium. We hereby describe the first reported case of an adolescent female with Cus hingoid features and morbid osteoporosis who was treated with mifepristone for its antiglucocorticoid effect (400 mg/day) in an attempt to prevent fur ther bone loss. The patient's striae, weight gain, and buffalo hump markedl y improved, and further bone loss was halted. However, with each of the two 6-month courses of mifepristone (9 months apart) she developed massive sim ple endometrial hyperplasia and a markedly enlarged uterus, This reversed t o normal after cessation of mifepristone treatment. In conclusion, High doses of the antiprogestagen mifepristone over a prolon ged period of time may promote an unopposed oestrogen milieu leading to end ometrial hyperplasia, Therefore, interval pelvic imaging in women who recei ve long-term mifepristone may be prudent.