Proven and potential clinical applications of mifpristone (RU486)

Reviews in Endocrine and Metabolic Disorders

Volumn 3, Issue 3, 2002, Pages 267-275

  Spitz, Irving M ^a  

^a SHAARE ZEDEK MEDICAL CENTER   (Israel)

Author keywords

Antiprogestins; Cervical dilation; Endometriosis; Mifepristone; Myoma; Pregnancy termination; Progesterone antagonists; Progesterone receptor modulators

Indexed keywords

11BETA (4 ACETYLPHENYL) 17BETA HYDROXY 17ALPHA (1,1,2,2,2 PENTAFLUOROETHYL)ESTRA 4,9 DIEN 3 ONE; ANTIGESTAGEN; ASOPRISNIL; J 956; MIFEPRISTONE; ONAPRISTONE; PROGESTERONE; PROGESTERONE RECEPTOR MODULATOR; UNCLASSIFIED DRUG; ZK 200211; ZK200211;

ANOREXIA; BREAST CARCINOMA; CONGENITAL DISORDER; CONTRACEPTION; CUSHING DISEASE; DRUG MECHANISM; ENDOCRINE DISEASE; ENDOMETRIOSIS; FATIGUE; FERTILIZATION IN VITRO; FETUS DEATH; GYNECOMASTIA; HORMONE SUBSTITUTION; HUMAN; HYPOADRENALISM; HYPOTHYROIDISM; LABOR INDUCTION; LIBIDO; MENINGIOMA; NAUSEA; PREGNANCY TERMINATION; REVIEW; UTERINE CERVIX DILATATION; UTERUS BLEEDING; UTERUS MYOMA; VOMITING;

FEMALE; HUMANS; MIFEPRISTONE; UTERINE CONTRACTION;

EID: 0036746736     PISSN: 13899155     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1020032711706     Document Type: Review

References (75)

1. Philibert D, Deraedt R, Teutsch G. RU38486: A potent antiglucortoid in vivo. In: 8th International Congress of Pharmacology. Tokyo, Japan, 1981.
2. Philibert D. RU38486: An original multifaceted antihormone in vivo. In: Agarwal M, eds. Adrenal Steroid Antagonism. Berlin: Walter de Gruyter 1984;77-101.
3. Baulieu E. Contragestion and other clinical applications of RU486, an antiprogesterone at the receptor. Science 1989;245:1351-1357.
4. Spitz IM, Bardin CW. Mifepristone (RU486) - a modulator of progestin and glucocorticoid action. N Engl J Med 1993;329(6):404-412.
5. Spitz IM, Croxatto HB, Robbins A. Antiprogestins: Mechanism of action and contraceptive potential. Annu Rev Pharmacol Toxicol 1996;36:47-81.
6. Spitz IM. Preface: Progestins, progesterone receptor modulators and progesterone antagonists. Steroids 2000;65(10/11):543-544.
7. Elger W, Bartley J, Schneider B, Kaufmann G, Schubert G, Chwalisz K. Endocrine pharmacological characterization of progesterone antagonistic and progesterone receptor modulators with respect to PR-agonistic and antagonistic activity. Steroids 2000;65(10/11):713-723.
8. Chwalisz K, Brenner RM, Fuhrmann U, Hess-Stumpp H, Elger W. Antiproliferative effects of progesterone antagonists and progesterone receptor modulators on the endometrium. Steroids 2000;65(10/11):741-751.
9. Spitz IM, Chwalisz K. Progesterone receptor modulators in women's health. Steroids 2000;65(10/11):807-816.
10. Garfield RE, Blennerhassett MG, Miller SM. Control of myometrial contractility: Role and regulation of gap junctions. Oxf Rev Reprod Biol 1988;10:436-490.
11. Bygdeman M, Swahn ML. Progesterone receptor blockage. Effect on uterine contractility and early pregnancy. Contraception 1985;32(1):45-51.
12. Cheng L, Kelly RW, Thong KJ, Hume R, Baird DT. The effect of mifepristone (RU486) on the immunohistochemical distribution of prostaglandin E and its metabolite in decidual and chorionic tissue in early pregnancy. J Clin Endocrinol Metab 1993;77(3):873-877.
13. Cheng L, Kelly RW, Thong KJ, Hume R, Baird DT. The effects of mifepristone (RU486) on prostaglandin dehydrogenase in decidual and chorionic tissue in early pregnancy. Hum Reprod 1993;8(5):705-709.
14. Gravanis A, Schaison G, George M, de Brux J, Satyaswaroop PG, Baulieu EE, Robel P. Endometrial and pituitary responses to the steroidal antiprogestin RU486 in postmenopausal women. J Clin Endocrinol Metab 1985;60(1):156-163.
15. Hodgen GD, van Uem JF, Chillik CF, Danforth DR, Wolf JP, Neulen J, Williams RF, Chwalisz K. Non-competitive antioestrogenic activity of progesterone antagonists in primate models. Hum Reprod 1994;9(Suppl. 1):77-81.
16. Slayden OD, Zelinski Wooten MB, Chwalisz K, Stouffer RL, Brenner RM. Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137316: morphometric assessment of the uterus and oviduct. Hum Reprod 1998;13(2):269-277.
17. Chwalisz K, Stockemann K, Fritzemeier KH, Fuhrmann U. Modulation of oestrogenic effects by progesterone antagonists in the rat uterus. Hum Reprod Update 1998;4(5):570-583.
18. Newfield RS, Spitz IM, Isacson C, New MI. Long-term mifepristone (RU486) therapy resulting in massive benign endometrial hyperplasia. Clin Endocrinol (Oxf) 2001;54(3):399-404.
19. Grunberg SM, Rankin C, Townsend J, Ahamadi L. Phase III double blind randomized placebo-controlled study of mifepristone (RU) for the treatment of unresectable meningioma. Proceeding of ASCO, Thirty-Seventh Annual Meeting 2001;20:56a.
20. Herrmann W, Wyss R, Riondel A, Philibert D, Teutsch G, Sakiz E, Baulieu EE. Effet d'un steroide antiprogesterone chezla femme: interruption du cycle menstruel et de la grossesse au debut. CR Acad Sc Paris 1982;294:933-938.
21. Bygdeman M, Danielsson KG, Marions L, Swahn ML. Contraceptive use of antiprogestin. Eur J Contracept Reprod Health Care 1999;4(2):103-107.
22. Batista MC, Cartledge TP, Zellmer AW, Nieman LK, Loriaux DL, Merriam GR. The antiprogestin RU486 delays the midcycle gonadotropin surge and ovulation in gonadotropin-releasing hormone-induced cycles. Fertil Steril 1994;62(1):28-34.
23. Shoupe D, Mishell DR, Jr., Lahteenmaki P, Heikinheimo O, Birgerson L, Madkour H, Spitz IM. Effects of the antiprogesterone RU486 in normal women. I. Single-dose administration in the midluteal phase. Am J Obstet Gynecol 1987;157(6):1415-20.
24. Christin-Maitre S, Bouchard P, Spitz IM. Medical termination of pregnancy. New Engl J Med 2000;342(13):946-956.
25. Spitz IM, Bardin CW. Clinical pharmacology of RU486-an antiprogestin and antiglucocorticoid. Contraception 1993;48(5): 403-444.
26. Couzinet B, Le Strat N, Ulmann A, Baulieu EE, Schaison G. Termination of early pregnancy by the progesterone antagonist RU486 (Mifepristone). N Engl J Med 1986;315(25):1565-1570.
27. World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation. Termination of pregnancy with reduced doses of mifepristone. BMJ 1993;307(6903):532-537.
28. Robbins A, Spitz IM. Mifepristone: clinical pharmacology. Clin Obstet Gynecol 1996;39(2):436-450.
29. Prasad RN, Choolani M. Termination of early human pregnancy with either 50mg or 200mg single oral dose of mifepristone (RU486) in combination with either 0.5mg or 1.0mg vaginal gemeprost. Aust N Z J Obstet Gynaecol 1996;36(1):20-23.
30. Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med 1998;338(18):1241-1247.
31. Aubeny E, Peyron R, Larquier Turpin C, Renault M, Targosz V, Silvestre L, et al. Termination of early pregnancy (up to 63 days of amenorrhea) with mifepristone and increasing doses of misoprostol. Int J Fertil 1995;40(Suppl. 2):85-91.
32. World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation. Comparison of two doses of mifepristone in combinaton with misoprostol for early medical abortion: a randomised trial. Brit J Obstet Gynecol 2000;107:524-530.
33. Ashok PW, Penney GC, Flett GM, Templeton A. An effective regimen for early medical abortion: a report of 2000 consecutive cases. Hum Reprod 1998;13(10):2962-2965.
34. el Refaey H, Rajasekar D, Abdalla M, Calder L, Templeton A. Induction of abortion with mifepristone (RU486) and oral or vaginal misoprostol. N Engl J Med 1995;332(15):983-987.
35. Baird DT, Sukcharoen N, Thong KJ. Randomized trial of misoprostol and cervagem in combination with a reduced dose of mifepristone for induction of abortion. Hum Reprod 1995;10(6):1521-1527.
36. Urquhart D, Templeton A, Shinwei F, Chapman M, Hawkins K, McGarry J, Rodger M, Baird D, Bjornsson S. The efficacy and tolerance of mifepristone and prostaglandin in termination of pregnancy of less than 63 days gestation; UK multicentre study-final results. Contraception 1997;55:1-5.
37. Schaff EA, Fielding SL, Westhoff C, Ellertson C, Eisinger SH, Stadalius LS, Fuller L. Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: A randomized trial. JAMA 2000;284(15):1948-1953.
38. Creinin MD, Schwartz JL, Pymar HC, Fink W. Efficacy of mifepristone followed on the same day by misoprostol for early termination of pregnancy: report of a randomised trial. BJOG 2001;108(5):469-473.
39. Rodger MW, Baird DT. Blood loss following induction of early abortion using mifepristone (RU486) and a prostaglandin analogue (gemeprost). Contraception 1989;40(4):439-447.
40. Cohn M, Stewart P. Pretreatment of the primigravid uterine cervix with mifepristone 30 h prior to termination of pregnancy: a double blind study. Br J Obstet Gynaecol 1991;98(8):778-782.
41. Urquhart DR, Templeton AA. Mifepristone (RU486) for cervical priming prior to surgically induced abortion in the late first trimester. Contraception 1990;42(2):191-199.
42. Urquhart DR, Templeton AA. The use of mifepristone prior to prostaglandin-induced mid-trimester abortion. Hum Reprod 1990;5(7):883-886.
43. Ashok PW, Templeton AA. Nonsurgical mid-trimester termination of pregnancy: a review of 500 consecutive cases. Br J Obstet Gynaecol 1999;106(7):706-710.
44. Cabrol D, Dubois C, Cronje H, Gonnet JM, Guillot M, Maria B, Moodley J, Oury JF, Thoulon JM, Treisser A. Induction of labor with mifepristone (RU486) in intrauterine fetal death. Am J Obstet Gynecol 1990;163(2):540-542.
45. Elliott CL, Brennand JE, Calder AA. The effects of mifepristone on cervical ripening and labor induction in primigravidae. Obstet Gynecol 1998;92(5):804-809.
46. Frydman R, Lelaidier C, Baton Saint Mleux C, Fernandez H, Vial M, Bourget P. Labor induction in women at term with mifepristone (RU486): a double-blind, randomized, placebo-controlled study. Obstet Gynecol 1992;80(6):972-975.
47. Hill NC, Selinger M, Ferguson J, MacKenzie IZ. The placental transfer of mifepristone (RU486) during the second trimester and its influence upon maternal and fetal steroid concentrations. Br J Obstet Gynaecol 1990;97(5):406-411.
48. Kettel LM, Murphy AA, Morales AJ, Rivier J, Vale W, Yen SS. Rapid regression of uterine leiomyomas in response to daily administration of gonadotropin-releasing hormone antagonist [see comments]. Fertil Steril 1993;60(4):642-646.
49. Kettel LM, Murphy AA, Morales AJ, Ulmann A, Baulieu EE, Yen SS. Treatment of endometriosis with the antiprogesterone mifepristone (RU486). Fertil Steril 1996;65(1):23-28.
50. Kettel LM, Murphy AA, Morales AJ, Yen SS. Preliminary report on the treatment of endometriosis with low-dose mifepristone (RU486). Am J Obstet Gynecol 1998;178(6):1151-1156.
51. Yen SSC. Use of antiprogestins in the management of endometriosis and leiomyoma. In: Donaldson, MS, Dorflinger, L, Brown, SS, Benet, LZ eds. Clinical Applications of Mifepristone (RU496) and other Antiprogestins. Washington DC: National Academy Press, 1993;189-209.
52. Murphy AA, Castellano PZ. RU486: pharmacology and potential use in the treatment of endometriosis and leiomyomata uteri. Curr Opin Obstet Gynecol 1994;6(3):269-278.
53. Yang Y, Zheng S, Li K. Treatment of Uterine Leimyoma by two different doses of mifepristone. Chin J Obstet Gynecol 1996;31(10):624-626.
54. Spitz IM, Van Look PF, Coelingh Bennink HJ. The use of progesterone antagonists and progesterone receptor modulators in contraception. Steroids 2000;65(10/11):817-824.
55. Croxatto HB, Salvatierra AM, Croxatto HD, Fuentealba B. Effects of continuous treatment with low dose mifepristone throughout one menstrual cycle. Hum Reprod 1993;8(2):201-207.
56. Cameron ST, Critchley HO, Thong KJ, Buckley CH, Williams AR, Baird DT. Effects of daily low dose mifepristone on endometrial maturation and proliferation. Hum Reprod 1996;11(11):2518-2526.
57. Brown A, Mayo A, Smith KB, Cheng L, Lin S, Baird DT. Daily low dose mifepristone has contraceptive potential by suppressing ovulation and menstruation: a study over 4 months in Edinburgh and Shanghai. Int Jnl Obstets Gynec 2000;70(Suppl. 1):22.
58. Marions L, Danielsson KG, Swahn ML, Bygdeman M. Contraceptive efficacy of low doses of mifepristone. Fertil Steril 1998;70(5):813-816.
59. Marions L, Viski S, Gemzell-Danielsson K, Resch BA, Swahn ML, Bygdeman M, Kovacs L. Contraceptive efficacy of daily administration of 0.5 mg mifepristone. Hum Reprod 1999;14(11):2788-2790.
60. Gemzell Danielsson K, Swahn ML, Svalander P, Bygdeman M. Early luteal phase treatment with mifepristone (RU486) for fertility regulation. Hum Reprod 1993;8(6):870-873.
61. Swahn ML, Bygdeman M, Chen JK, Gemzell Danielsson K, Song S, Yang QY, Yang PJ, Qian ML, Chang WF. Once-a-month treatment with a combination of mifepristone and the prostaglandin analogue misoprostol. Hum Reprod 1999;14(2):485-488.
62. World Health Organization Task Force on Post-Ovulatory Methods of Fertility Regulation. Menstrual regulation by mifepristone plus prostaglandin: Results from a multicentre trial. Hum Reprod 1995;10(2):308-314.
63. World Health Organization Task Force on Postovulatory Methods of Fertility Regulation. Comparison of three single doses of mifepristone as emergency contraception: a randomised trial. Lancet 1999;353(9154):697-702.
64. Messinis IE, Krishnan M, Kazem R, Khadilkar S, Templeton AA. Effect of mifepristone on folliculogenesis in women treated with recombinant FSH. Clin Endocrinol Oxf 1997;46(3):309-314.
65. Hegele Hartung C, Mootz U, Beier HM. Luteal control of endometrial receptivity and its modification by progesterone antagonists. Endocrinology 1992;131(5):2446-2460.
66. Paulson RJ, Sauer MV, Lobo RA. Potential enhancement of endometrial receptivity in cycles using controlled ovarian hyperstimulation with antiprogestins: a hypothesis. Fertil Steril 1997;67(2):321-325.
67. Nieman LK, Chrousos GP, Kellner C, Spitz IM, Nisula BC, Cutler GB, et al. Successful treatment of Cushing's syndrome with the glucocorticoid antagonist RU486. J Clin Endocrinol Metab 1985;61(3):536-540.
68. Regelson W, Loria R, Kalimi M. Beyond 'abortion': RU-486 and the needs of the crisis constituency. JAMA 1990;264(8):1026- 1027.
69. Klijn JG, Setyono Han B, Foekens JA. Progesterone antagonists and progesterone receptor modulators in the treatment of breast cancer. Steroids 2000;65(10-11):825-830.
70. Grunberg SM, Weiss MH, Spitz IM, Ahamadi J, Sadun A, Russell CA, et al. Treatment of unresectable meningiomas with the antiprogesterone agent mifepristone. J Neurosurg 1991;74:861-864.
71. Takiyama Y, Tanaka H, Takiyama Y, Makino I. The effects of hydrocortisone and RU486 (Mifepristone) on iodide uptake in porcine thyroid cells in primary culture. Endocrinology 1994:1972-1979.
72. Gonzalez CH, Marques Dias MJ, Kim CA, Sugayama SM, Da Paz JA, Huson SM, Holmes LB. Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy. Lancet 1998;351(9116):1624-1627.
73. Gonzalez CH, Vargas FR, Perez AB, Kim CA, Brunoni D, Marques Dias MJ, Leone CR, Correa Neto J, Llerena Junior JC, de Almeida JC. Limb deficiency with or without Mobius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy. Am J Med Genet 1993;47(1):59-64.
74. Fonseca W, Alencar AJ, Mota FS, Coelho HL. Misoprostol and congenital malformations. Lancet 1991;338(8758):56.
75. Coelingh Bennink HJT. The Jerusalem Declaration. Steroids 2000;65:839-840.