The use of anti-progesterones as a medical IUD
Nieman, L.K.; Loriaux, D.L.
Bailliere's Clinical Obstetrics and Gynaecology 2(3): 609-616
1988
ISSN/ISBN: 0950-3552 PMID: 3233821 DOI: 10.1016/s0950-3552(88)80047-6Document Number: 368891
Preliminary studies on the use of mifepristone (RU-486, Roussel-Uclaf) as a luteolytic contraceptive have entailed dose response, cycle control, contraceptive efficacy and toxicity studies in women and men. Mifepristone is a 19-nor-steroid with an affinity for the progesterone receptor 3 times that of progesterone, and an affinity for the glucocorticoid receptor 2 times that of dexamethasone. 9 small studies have confirmed that mifepristone will induce endometrial shedding when given orally to women after the 6th luteal day, but not before the 5th day. It has no effect on non-ovulatory cycles, since it acts by competing with progesterone on the secretory epithelium. Generally across various dose studies there is a dose response effect: Mifepristone at 1 mg/kg, about 50 mg daily, brings on bleeding in most women. Luteolysis occurs on about Day 26 of the cycle normally, so it is not possible to prove that the drug caused luteolysis. It is likely, however, that if luteolysis were complete, the next cycle will be normal. In case of incomplete luteolysis in a cycle treated with Mifepristone, the subsequent cycle will be prolonged. Studies on the mechanism of action of Mifepristone as a luteolytic have shown that menses will occur even if exogenous hCG is given to sustain progesterone levels. Another bleeding occurs when progesterone levels fall below 2.5 ng/ml. It has been reported that mifepristone disrupts the amplitude and frequency of the LH pulse, suggesting that it has mixed agonist- antagonist actions on the pituitary. Results are still mixed on whether Mifepristone consistently prevents pregnancy in fertile cycles. No adverse or toxic effects have been observed in women given as much as 200 mg/kg for breast cancer, except for moderate hypokalemia. Non-oral administration routes are being investigated to lower the dose and avoid the 1st pass effect. Mifepristone may prove to be an effective luteolytic, but may have to be taken with sophisticated cycle monitoring.