Mifepristone: Where do we come from and where are we going? Clinical development over a quarter of a century

Contraception

Volumn 82, Issue 5, 2010, Pages 442-452

  Spitz, Irving M ^a  

^a BEN GURION UNIVERSITY OF THE NEGEV   (Israel)

Author keywords

Contraception; Endometriosis; Fibroids; Mifepristone; Pregnancy termination; Progesterone receptor antagonists; Progesterone receptor modulators

Indexed keywords

17ALPHA ACETOXY 11BETA (4 DIMETHYLAMINOPHENYL) 21 METHOXY 19 NORPREGNA 4,9 DIENE 3,20 DIONE; ASOPRISNIL; ESTRADIOL; ESTROGEN; GESTAGEN; JNJ 17072341; LEUPRORELIN; MIFEPRISTONE; ONAPRISTONE; PLACEBO; PROGESTERONE RECEPTOR; SEX HORMONE; ULIPRISNIL ACETATE; UNCLASSIFIED DRUG; ZK 137316;

AMENORRHEA; BLEEDING; BREAST CANCER; CONTRACEPTION; DISTRESS SYNDROME; DRUG ACTIVITY; DRUG EFFICACY; DRUG MECHANISM; EMERGENCY CONTRACEPTION; ENDOMETRIAL DISEASE; ENDOMETRIAL THICKENING; ENDOMETRIOSIS; ESTRADIOL BLOOD LEVEL; FETUS DEATH; FOLLICULAR PHASE; GENE EXPRESSION; HUMAN; LABOR INDUCTION; LEIOMYOMA; LIVER FUNCTION; LONG TERM CARE; LOW DRUG DOSE; LUTEINIZING HORMONE RELEASE; MENSTRUATION; NONHUMAN; OVULATION; PAIN; PREGNANCY TERMINATION; QUALITY OF LIFE; REPRODUCTIVE HEALTH; REVIEW; TRANSGENE; UTERUS BLEEDING; UTERUS MYOMA;

ABORTIFACIENT AGENTS, STEROIDAL; ABORTION, LEGAL; ANIMALS; ANTINEOPLASTIC AGENTS, HORMONAL; CONTRACEPTIVES, POSTCOITAL, SYNTHETIC; FEMALE; GENITAL DISEASES, FEMALE; HUMANS; MIFEPRISTONE; PREGNANCY; RECEPTORS, PROGESTERONE; WOMEN'S HEALTH;

EID: 77957748919     PISSN: 00107824     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.contraception.2009.12.012     Document Type: Review

References (135)

1. Spitz I.M. Progestins, progesterone antagonists and progesterone receptor modulators Steroids 65 2000 543 544
2. Philibert D., Deraedt R., and Teutsch G. RU 38486: a potent antiglucocorticoid in vivo The VII International Congress of Pharmacology; 1981 1981 Tokyo Japan
3. Berrodin T.J., Jelinsky S.A., and Graciani N. Novel progesterone receptor modulators with gene selective and context-dependent partial agonism Biochem Pharmacol 77 2009 204 215
4. Winneker R.C., Fensome A., Zhang P., Yudt M.R., McComas C.C., and Unwalla R.J. A new generation of progesterone receptor modulators Steroids 73 2008 689 701
5. Giangrande P.H., and McDonnell D.P. The A and B isoforms of the human progesterone receptor: two functionally different transcription factors encoded by a single gene Recent Prog Horm Res 54 1999 291 313 [discussion-4]
6. Kastner P., Krust A., and Turcotte B. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B EMBO J 9 1990 1603 1614
7. Wei L.L., Hawkins P., Baker C., Norris B., Sheridan P.L., and Quinn P.G. An amino-terminal truncated progesterone receptor isoform, PRc, enhances progestin-induced transcriptional activity Mol Endocrinol 10 1996 1379 1387
8. Condon J.C., Hardy D.B., Kovaric K., and Mendelson C.R. Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-kappaB may contribute to the onset of labor through inhibition of PR function Mol Endocrinol 20 4 2006 764 775
9. Mulac-Jericevic B., and Conneely O.M. Reproductive tissue selective actions of progesterone receptors Reproduction 128 2004 139 146
10. Vegeto E., Allan G.F., Schrader W.T., Tsai M.J., McDonnell D.P., and O'Malley B.W. The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor Cell 69 1992 703 713
11. Smith C.L., and O'Malley B.W. Coregulator function: a key to understanding tissue specificity of selective receptor modulators Endocr Rev 25 2004 45 71
12. Wagner B.L., Norris J.D., Knotts T.A., Weigel N.L., and McDonnell D.P. The nuclear corepressors NCoR and SMRT are key regulators of both ligand-and 8-bromo-cyclic AMP-dependent transcriptional activity of the human progesterone receptor Mol Cell Biol 18 1998 1369 1378
13. Madauss K.P., Grygielko E.T., and Deng S.J. A structural and in vitro characterization of asoprisnil: a selective progesterone receptor modulator Mol Endocrinol 21 2007 1066 1081
14. Spitz I.M., and Bardin C.W. Mifepristone (RU 486)-a modulator of progestin and glucocorticoid action N Engl J Med 329 1993 404 412
15. Johannisson E., Oberholzer M., Swahn M.L., and Bygdeman M. Vascular changes in the human endometrium following the administration of the progesterone antagonist RU 486 Contraception 39 1989 103 117
16. Garfield R.E., Blennerhassett M.G., and Miller S.M. Control of myometrial contractility: role and regulation of gap junctions Oxf Rev Reprod Biol 10 1988 436 490
17. Bygdeman M., and Swahn M.L. Progesterone receptor blockage. Effect on uterine contractility and early pregnancy Contraception 32 1985 45 51
18. Cheng L., Kelly R.W., Thong K.J., Hume R., and Baird D.T. The effects of mifepristone (RU486) on prostaglandin dehydrogenase in decidual and chorionic tissue in early pregnancy Hum Reprod 8 1993 705 709
19. Cheng L., Kelly R.W., Thong K.J., Hume R., and Baird D.T. 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 77 1993 873 877
20. Chwalisz K., and Garfield R.E. New molecular challenges in the induction on cervical ripening Hum Reprod 13 1998 245 252
21. Vaisanen-Tommiska M., Butzow R., Ylikorkala O., and Mikkola T.S. Mifepristone-induced nitric oxide release and expression of nitric oxide synthases in the human cervix during early pregnancy Hum Reprod 21 2006 2180 2184
22. Hodgen G.D., van Uem J.F., and Chillik C.F. Non-competitive anti-oestrogenic activity of progesterone antagonists in primate models Hum Reprod 9 Suppl 1 1994 77 81
23. Neulen J., Williams R.F., Breckwoldt M., Chwalisz K., Baulieu E.E., and Hodgen G.D. Non-competitive anti-oestrogenic actions of progesterone antagonists in primate endometrium: enhancement of oestrogen and progesterone receptors with blockade of post-receptor proliferative mechanisms Hum Reprod 11 1996 1533 1537
24. Slayden O.D., and Brenner R.M. RU 486 action after estrogen priming in the endometrium and oviducts of rhesus monkeys (Macaca mulatta) J Clin Endocrinol Metab 78 1994 440 448
25. Brenner R.M., Slayden O.D., and Critchley H.O. Anti-proliferative effects of progesterone antagonists in the primate endometrium: a potential role for the androgen receptor Reproduction 124 2002 167 172
26. Slayden O.D., Zelinski-Wooten M.B., Chwalisz K., Stouffer R.L., and Brenner R.M. Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137 316: morphometric assessment of the uterus and oviduct Hum Reprod 13 1998 269 277
27. Slayden O.D., Carroll R., Mah K., and Brenner R.M Exogenous androgen blocks endometrial growth in primates: relevance to the antiproliferative effects of progesterone antagonists SGI 53rd Annual Meeting; 2006; Toronto, Ontario, Canada: Elsevier 2006 851
28. Slayden O.D., and Brenner R.M Flutamide counteracts the antiproliferative effects of antiprogestins in the primate endometrium J Clin Endocrinol Metab 88 2003 946 949
29. Spitz I.M. Progesterone receptor antagonists E. Ottow, H. Weinmann, Nuclear receptors as drug targets 2008 WILEY-VCH Verlag GmbH and Co. KgaA Weinheim
30. Narvekar N, Critchley HO, Cheng L, and Baird DT Mifepristone-induced amenorrhoea is associated with an increase in microvessel density and glucocorticoid receptor and a decrease in stromal vascular endothelial growth factor Hum Reprod 21 2006 2312 2318
31. Shoupe D., Mishell D.R. Jr., Page M.A., Madkour H., Spitz I.M., and Lobo R.A. Effects of the antiprogesterone RU 486 in normal women. II. Administration in the late follicular phase Am J Obstet Gynecol 157 1987 1421 1426 (Pubitemid 18022869)
32. Cameron S.T., Critchley H.O., Thong K.J., Buckley C.H., Williams A.R., and Baird D.T. Effects of daily low dose mifepristone on endometrial maturation and proliferation Hum Reprod 11 1996 2518 2526
33. Christin-Maitre S., Bouchard P., and Spitz I.M. Medical termination of pregnancy New Engl J Med 342 2000 946 956
34. Fjerstad M., Sivin I., Lichtenberg E.S., Trussell J., Cleland K., and Cullins V. Effectiveness of medical abortion with mifepristone and buccal misoprostol through 59 gestational days Contraception 80 2009 282 286
35. Winikoff B., Dzuba I.G., and Creinin M.D. Two distinct oral routes of misoprostol in mifepristone medical abortion: a randomized controlled trial Obstet Gynecol 112 2008 1303 1310
36. Spitz I.M. Mifepristone for the medical termination of pregnancy DS Basow, UpToDate 2009 UpToDate Waltham, MA
37. Bartz D., and Goldberg A. Medication abortion Clin Obstet Gynecol 52 2009 140 150
38. Spitz I.M. Progesterone receptor antagonists and selective progesterone receptor modulators; proven and potential clinical indications Expert Rev Obstet Gynecol 2 2007 227 242
39. Fischer M., Bhatnagar J., and Guarner J. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion N Engl J Med 353 2005 2352 2360
40. Sinave C., Le Templier G., Blouin D., Leveille F., and Deland E. Toxic shock syndrome due to Clostridium sordellii: a dramatic postpartum and postabortion disease Clin Infect Dis 35 2002 1441 1443
41. van der Schoot P. Treatment with mifepristone (RU486) and oestradiol facilitates the development of genital septic disease after copulation in female rats Hum Reprod 7 1992 601 605
42. Miech R.P. Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii Ann Pharmacother 39 2005 1483 1488
43. Tait A.S., Dalton M., Geny B., D'Agnillo F., Popoff M.R., and Sternberg E.M. The large clostridial toxins from Clostridium sordellii and C. difficile repress glucocorticoid receptor activity Infect Immun 75 2007 3935 3940
44. Aronoff D.M., Hao Y., and Chung J. Misoprostol impairs female reproductive tract innate immunity against Clostridium sordellii J Immunol 180 2008 8222 8230
45. Fiala C., and Gemzel-Danielsson K. Review of medical abortion using mifepristone in combination with a prostaglandin analogue Contraception 74 2006 66 86
46. Fjerstad M., Trussell J., Sivin I., Lichtenberg E.S., and Cullins V. Rates of serious infection after changes in regimens for medical abortion N Engl J Med 361 2009 145 151
47. Lievre M., and Sitruk-Ware R. Meta-analysis of 200 or 600 mg mifepristone in association with two prostaglandins for termination of early pregnancy Contraception 80 2009 95 100
48. Ashok P.W., and Templeton A. Nonsurgical mid-trimester termination of pregnancy: a review of 500 consecutive cases Br J Obstet Gynaecol 106 1999 706 710
49. Bartley J., and Baird D.T. A randomised study of misoprostol and gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy BJOG 109 2002 1290 1294
50. Asch R.H., Weckstein L.N., Balmaceda J.P., Rojas F., Spitz I.M., and Tadir Y. Non-surgical expulsion of non-viable early pregnancy: a new application of RU 486 Hum Reprod 5 1990 481 483
51. Lelaidier C., Baton Saint Mleux C., Fernandez H., Bourget P., and Frydman R. Mifepristone (RU 486) induces embryo expulsion in first trimester non-developing pregnancies: a prospective randomized trial Hum Reprod 8 1993 492 495
52. Schaff E.A., Fielding S.L., Eisinger S., and Stadalius L. Mifepristone and misoprostol for early abortion when no gestational sac is present Contraception 63 2001 251 254
53. el Refaey H., Hinshaw K., Henshaw R., Smith N., and Templeton A. Medical management of missed abortion and anembryonic pregnancy BMJ 305 1992 1399
54. Wagaarachchi P.T., Ashok P.W., Narvekar N., Smith N.C., and Templeton A. Medical management of early fetal demise using a combination of mifepristone and misoprostol Hum Reprod 16 2001 1849 1853
55. Wagaarachchi P.T., Ashok P.W., Smith N.C., and Templeton A. Medical management of early fetal demise using sublingual misoprostol BJOG 109 2002 462 465
56. Nielsen S., and Hahlin M. Expectant management of first-trimester spontaneous abortion Lancet 345 1995 84 86
57. Nielsen S., Hahlin M., and Platz Christensen J. Randomised trial comparing expectant with medical management for first trimester miscarriages Br J Obstet Gynaecol 106 1999 804 807
58. Elati A., and Weeks A.D. The use of misoprostol in obstetrics and gynaecology BJOG 116 Suppl 1 2009 61 69
59. Cabrol D., Dubois C., and Cronje H. Induction of labor with mifepristone (RU 486) in intrauterine fetal death Am J Obstet Gynecol 163 1990 540 542
60. Wagaarachchi P.T., Ashok P.W., Narvekar N.N., Smith N.C., and Templeton A. Medical management of late intrauterine death using a combination of mifepristone and misoprostol BJOG 109 4 2002 443 447
61. Hapangama D., and Neilson J.P. Mifepristone for induction of labour Cochrane Database Syst Rev 2009 CD002865
62. Gronlund A., Gronlund L., Clevin L., Andersen B., Palmgren N., and Lidegaard O. Management of missed abortion: comparison of medical treatment with either mifepristone+misoprostol or misoprostol alone with surgical evacuation. A multi-center trial in Copenhagen county, Denmark Acta Obstet Gynecol Scand 81 2002 1060 1065
63. Goldberg A.B., Greenberg M.B., and Darney P.D. Misoprostol and pregnancy N Engl J Med 344 2001 38 47
64. 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 10 1995 308 314
65. Xiao B., von Hertzen H., Zhao H., and Piaggio G. Menstrual induction with mifepristone and misoprostol Contraception 68 2003 489 494
66. 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 353 1999 697 702
67. Xiao B.L., von Hertzen H., Zhao H., and Piaggio G. A randomized double-blind comparison of two single doses of mifepristone for emergency contraception Hum Reprod 17 2002 3084 3089
68. von Hertzen H., Piaggio G., and Ding J. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial Lancet 360 2002 1803 1810
69. Cheng L., Gulmezoglu A.M., Piaggio G., Ezcurra E., and Van Look P.F. Interventions for emergency contraception Cochrane Database Syst Rev 2008 CD001324
70. Steinauer J., Pritts E.A., Jackson R., and Jacoby A.F. Systematic review of mifepristone for the treatment of uterine leiomyomata Obstet Gynecol 103 2004 1331 1336
71. Eisinger S.H., Bonfiglio T., Fiscella K., Meldrum S., and Guzick D.S. Twelve-month safety and efficacy of low-dose mifepristone for uterine myomas J Minim Invasive Gynecol 12 2005 227 233
72. Eisinger S.H., Meldrum S., Fiscella K., le Roux H.D., and Guzick D.S. Low-dose mifepristone for uterine leiomyomata Obstet Gynecol 101 2003 243 250
73. Fiscella K., Eisinger S.H., Meldrum S., Feng C., Fisher S.G., and Guzick D.S. Effect of mifepristone for symptomatic leiomyomata on quality of life and uterine size: a randomized controlled trial Obstet Gynecol 108 2006 1381 1387
74. Wiehle R.D., Goldberg J., Brodniewicz T., Jarus-Dziedzic K., and Jabiry-Zieniewicz Z. Effects of a new progesterone receptor modulator, CDB-4124, on fibroid size and uterine bleeding US Obstetrics and Gynaecology 3 1 2008 17 20
75. Chwalisz K., Larsen L., Mattia-Goldberg C., Edmonds A., Elger W., and Winkel C.A. A randomized, controlled trial of asoprisnil, a novel selective progesterone receptor modulator, in women with uterine leiomyomata Fertil Steril 87 6 2007 1399 1412
76. Levens E.D., Potlog-Nahari C., and Armstrong A.Y. CDB-2914 for uterine leiomyomata treatment: a randomized controlled trial Obstet Gynecol 111 2008 1129 1136
77. Bagaria M., Suneja A., Vaid N.B., Guleria K., and Mishra K. Low-dose mifepristone in treatment of uterine leiomyoma: a randomised double-blind placebo-controlled clinical trial Aust N Z J Obstet Gynaecol 49 2009 77 83
78. Engman M., Granberg S., Williams A.R., Meng C.X., Lalitkumar P.G., and Gemzell-Danielsson K. Mifepristone for treatment of uterine leiomyoma. A prospective randomized placebo controlled trial Hum Reprod 24 8 2009 1870 1879
79. Eisinger S.H., Fiscella J., Bonfiglio T., Meldrum S., and Fiscella K. Open-label study of ultra low-dose mifepristone for the treatment of uterine leiomyomata Eur J Obstet Gynecol Reprod Biol 146 2 2009 215 218
80. Kettel L.M., Murphy A.A., Mortola J.F., Liu J.H., Ulmann A., and Yen S.S. Endocrine responses to long-term administration of the antiprogesterone RU486 in patients with pelvic endometriosis Fertil Steril 56 1991 402 407
81. Kettel L.M., Murphy A.A., Morales A.J., and Yen S.S. Preliminary report on the treatment of endometriosis with low-dose mifepristone (RU 486) Am J Obstet Gynecol 178 1998 1151 1156
82. Kettel L.M., Murphy A.A., Morales A.J., Ulmann A., Baulieu E.E., and Yen S.S. Treatment of endometriosis with the antiprogesterone mifepristone (RU486) Fertil Steril 65 1996 23 28
83. Spitz IM, Wiehle RD, and van As A. Progesterone receptor modulators in endometriosis: a new therapeutic option J. Garcia Velasco, B. Kizk, Textbook of endometriosis 2009 Jaypee Brothers Medical Publishers Ltd. India 225 234
84. Batista M.C., Cartledge T.P., Zallmer A.W., Nieman L.K., Merriam G.R., and Loriaux D.L. Evidence for a critical role of progesterone in the regulation of the midcyle gonadotropin surge and ovulation J Clin Endocrinol Metab 74 1992 565 570
85. Croxatto H.B., Kovacs L., and Massai R. Effects of long-term low-dose mifepristone on reproductive function in women Hum Reprod 13 1998 793 798
86. Croxatto H.B., Salvatierra A.M., Croxatto H.D., and Fuentealba B. Effects of continuous treatment with low dose mifepristone throughout one menstrual cycle Hum Reprod 8 1993 201 207
87. Brown A., Cheng L., Lin S., and Baird D.T. Daily low-dose mifepristone has contraceptive potential by suppressing ovulation and menstruation: a double-blind randomized control trial of 2 and 5 mg per day for 120 days J Clin Endocrinol Metab 87 2002 63 70
88. Lakha F., Ho P.C., and Van der Spuy Z.M. A novel estrogen-free oral contraceptive pill for women: multicentre, double-blind, randomized controlled trial of mifepristone and progestogen-only pill (levonorgestrel) Hum Reprod 22 2007 2428 2436
89. Gemzell Danielsson K., Swahn M.L., Svalander P., and Bygdeman M. Early luteal phase treatment with mifepristone (RU 486) for fertility regulation Hum Reprod 8 1993 870 873
90. Hapangama D.K., Brown A., Glasier A.F., and Baird D.T. Feasibility of administering mifepristone as a once a month contraceptive pill Hum Reprod 16 2001 1145 1150
91. Agarwal M., Das V., Agarwal A., Pandey A., and Srivastava D. Evaluation of mifepristone as a once a month contraceptive pill Am J Obstet Gynecol 200 5 2009 e27 9
92. Spitz I.M., Croxatto H.B., Salvatierra A.M., and Heikinheimo O. Response to intermittent RU486 in women Fertil Steril 59 1993 971 975
93. Chen X., and Xiao B. Effect of once weekly administration of mifepristone on ovarian function in normal women Contraception 56 1997 175 180
94. Pei K., Xiao B., Jing X., Lu S., Wei L., and Zhao H. Weekly contraception with mifepristone Contraception 75 2007 40 44
95. Croxatto H.B., Salvatierra A.M., Fuentealba B., and Massai R. Contraceptive potential of a mifepristone-nomegestrol acetate sequential regimen in women Hum Reprod 13 1998 3297 3302
96. Massai R., Forcelledo M.L., Quinteros E., Fuentealba B., and Croxatto H. Anticoncepcion oral libre de estrogenos: Regimen secuencial antiprogestina- progestina Cuban J Public Health 29 Suppl 1 2003 R104
97. Critchley H, Williams A, and Cameron I Effects of asoprisnil, a selective progesterone receptor modulator (SPRM), in women with treatment resistant heavy menstrual bleeding SGI Annual Scientific Meeting; 2007; Reno, Nevada 2007 588
98. Cheng L., Zhu H., Wang A., Ren F., Chen J., and Glasier A. Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel Hum Reprod 15 2000 1969 1972
99. Massai M.R., Pavez M., Fuentealba B., Croxatto H.B., and d'Arcangues C. Effect of intermittent treatment with mifepristone on bleeding patterns in Norplant implant users Contraception 70 2004 47 54
100. Jain J.K., Nicosia A.F., Nucatola D.L., Lu J.J., Kuo J., and Felix J.C. Mifepristone for the prevention of breakthrough bleeding in new starters of depo-medroxyprogesterone acetate Steroids 68 2003 1115 1119
101. Weisberg E., Hickey M., and Palmer D. A pilot study to assess the effect of three short-term treatments on frequent and/or prolonged bleeding compared to placebo in women using Implanon Hum Reprod 21 2006 295 302
102. Weisberg E., Hickey M., and Palmer D. A randomized controlled trial of treatment options for troublesome uterine bleeding in Implanon users Hum Reprod 24 2009 1852 1861
103. Morison N.B., Kaitu'u-Lino T.J., Fraser I.S., and Salamonsen L.A. Stimulation of epithelial repair is a likely mechanism for the action of mifepristone in reducing duration of bleeding in users of progestogen-only contraceptives Reproduction 136 2008 267 274
104. Klijn J.G., Setyono Han B., and Foekens J.A. Progesterone antagonists and progesterone receptor modulators in the treatment of breast cancer Steroids 65 2000 825 830
105. Taplin M.E., Manola J., and Oh W.K. A phase II study of mifepristone (RU-486) in castration-resistant prostate cancer, with a correlative assessment of androgen-related hormones BJU Int 101 2008 1084 1089
106. Wiehle R.D., Christov K., and Mehta R. Anti-progestins suppress the growth of established tumors induced by 7,12-dimethylbenz(a)anthracene: comparison between RU486 and a new 21-substituted-19-nor-progestin Oncol Rep 18 2007 167 174
107. Robertson J.F., Willsher P.C., Winterbottom L., Blamey R.W., and Thorpe S. Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer Eur J Cancer 35 1999 214 218
108. Attardi B.J., Burgenson J., Hild S.A., and Reel J.R. In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone J Steroid Biochem Mol Biol 88 2004 277 288
109. Engman M., Skoog L., Soderqvist G., and Gemzell-Danielsson K. The effect of mifepristone on breast cell proliferation in premenopausal women evaluated through fine needle aspiration cytology Hum Reprod 23 2008 2072 2079
110. Poole A.J., Li Y., Kim Y., Lin S.C., Lee W.H., and Lee E.Y. Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist Science 314 2006 1467 1470
111. Rocereto T.F., Saul H.M., Aikins J.A. Jr., and Paulson J. Phase II study of mifepristone (RU486) in refractory ovarian cancer Gynecol Oncol 77 2000 429 432
112. Koivisto-Korander R., Leminen A., and Heikinheimo O. Mifepristone as treatment of recurrent progesterone receptor-positive uterine leiomyosarcoma Obstet Gynecol 109 2 Pt2 2007 512 514
113. Ramondetta L.M., Johnson A.J., and Sun C.C. Phase 2 trial of mifepristone (RU-486) in advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma Cancer 2009
114. Arnett-Mansfield R.L., DeFazio A., Mote P.A., and Clarke C.L. Subnuclear distribution of progesterone receptors A and B in normal and malignant endometrium J Clin Endocrinol Metab 89 2004 1429 1442
115. McGowan E.M., Saad S., Bendall L.J., Bradstock K.F., and Clarke C.L. Effect of progesterone receptor a predominance on breast cancer cell migration into bone marrow fibroblasts Breast Cancer Res Treat 83 2004 211 220
116. Shyamala G., Yang X., Silberstein G., Barcellos-Hoff M.H., and Dale E. Transgenic mice carrying an imbalance in the native ratio of A to B forms of progesterone receptor exhibit developmental abnormalities in mammary glands Proc Natl Acad Sci U S A 95 1998 696 701
117. Fleisch M.C., Chou Y.C., Cardiff R.D., Asaithambi A., and Shyamala G. Overexpression of progesterone receptor A isoform in mice leads to endometrial hyperproliferation, hyperplasia and atypia Mol Hum Reprod 15 2009 241 249
118. Check J.H., Dix E., and Sansoucie L. Support for the hypothesis that successful immunotherapy of various cancers can be achieved by inhibiting a progesterone associated immunomodulatory protein Med Hypotheses 72 2009 87 90
119. Check J.H., Dix E., Sansoucie L., and Check D. Mifepristone may halt progression of extensively metastatic human adenocarcinoma of the colon-case report Anticancer Res 29 2009 1611 1613
120. Srivastava M.D., Thomas A., Srivastava B.I., and Check J.H. Expression and modulation of progesterone induced blocking factor (PIBF) and innate immune factors in human leukemia cell lines by progesterone and mifepristone Leuk Lymphoma 48 2007 1610 1617
121. Check J.H., Sansoucie L., Chern J., Amadi N., and Katz Y. Mifepristone treatment improves length and quality of survival of mice with spontaneous leukemia Anticancer Res 29 2009 2977 2980
122. Wang X.J., Liefer K.M., Tsai S., O'Malley B.W., and Roop D.R. Development of gene-switch transgenic mice that inducibly express transforming growth factor beta1 in the epidermis Proc Natl Acad Sci U S A 96 1999 8483 8488
123. Nordstrom J.L. The antiprogestin-dependent GeneSwitch system for regulated gene therapy Steroids 68 2003 1085 1094
124. Unniappan S., Wideman R.D., and Donald C. Treatment of diabetes by transplantation of drug-inducible insulin-producing gut cells J Mol Med 87 2009 703 712
125. Oosman S.N., Lam A.W., and Harb G. Treatment of obesity and diabetes in mice by transplant of gut cells engineered to produce leptin Mol Ther 16 2008 1138 1145
126. Spitz I.M., Grunberg S., Chabbert-Buffet N., Lindenberg T., Gelber H., and Sitruk-Ware R. Management of patients receiving long term treatment with mifepristone Fertil Steril 84 2005 1719 1726
127. Heikinheimo O., Ranta S., Grunberg S., Lahteenmaki P., and Spitz I.M. Alterations in the pituitary-thyroid and pituitary-adrenal axes-consequences of long-term mifepristone treatment Metabolism 46 1997 292 296
128. Horne F.M., and Blithe D.L. Progesterone receptor modulators and the endometrium: changes and consequences Hum Reprod Update 13 2007 567 580
129. Mutter G.L., Bergeron C., and Deligdisch L. The spectrum of endometrial pathology induced by progesterone receptor modulators Mod Pathol 2008
130. Baird D.T., Brown A., Critchley H.O., Williams A.R., Lin S., and Cheng L. Effect of long-term treatment with low-dose mifepristone on the endometrium Hum Reprod 18 2003 61 68
131. Williams A.R., Critchley H.O., and Osei J. The effects of the selective progesterone receptor modulator asoprisnil on the morphology of uterine tissues after 3 months treatment in patients with symptomatic uterine leiomyomata Hum Reprod 22 2007 1696 1704
132. Newfield R.S., Spitz I.M., Isacson C., and New M.I. Long-term mifepristone (RU486) therapy resulting in massive benign endometrial hyperplasia Clin Endocrinol (Oxf) 54 2001 399 404
133. Carbonell Esteve J.L., Acosta R., Heredia B., Perez Y., Castaneda M.C., and Hernandez A.V. Mifepristone for the treatment of uterine leiomyomas: a randomized controlled trial Obstet Gynecol 112 2008 1029 1036
134. Ioffe O.B., Zaino R.J., and Mutter G.L. Endometrial changes from short-term therapy with CDB-4124, a selective progesterone receptor modulator Mod Pathol 2009
135. Nieman L.K. The proof of evidence: ulipristal acetate phase 2 clinical trials 8th Congress of the European Society of Gynecology 2009 [Abstract: Rome, 9-13 September]