Selective progesterone receptor modulators 1: Use during pregnancy

Expert Opinion on Pharmacotherapy

Volumn 9, Issue 14, 2008, Pages 2459-2472

  Benagiano, Giuseppe ^a   Bastianelli, Carlo ^b   Farris, Manuela ^b  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b POLICLINICO UMBERTO I   (Italy)

Author keywords

Antiprogestins; Induction of labour; Management of miscarriage; Medical termination of pregnancy; Selective progesterone receptor modulators

Indexed keywords

11BETA [4 (DIMETHYLAMINO)PHENYL] 4',5' DIHYDRO 6BETA METHYLSPIRO[ESTRA 4,9 DIENE 17BETA,2'(3'H) FURAN] 3 ONE; 17ALPHA ACETOXY 11BETA (4 DIMETHYLAMINOPHENYL) 21 METHOXY 19 NORPREGNA 4,9 DIENE 3,20 DIONE; ANTIGESTAGEN; ASOPRISNIL; CBD 2914; CBD 4124; GEMEPROST; METHOTREXATE; MIFEPRISTONE; MISOPROSTOL; ONAPRISTONE; ORG 33628; PLACEBO; PROGESTERONE RECEPTOR MODULATOR; PROSTAGLANDIN; PROSTAGLANDIN E; PROSTAGLANDIN F2 ALPHA; STEROID HORMONE RECEPTOR BLOCKING AGENT; ULIPRISNIL ACETATE; UNCLASSIFIED DRUG;

BACTERIAL INFECTION; BREAST CANCER; CANCER HORMONE THERAPY; CLINICAL TRIAL; CONTRACEPTION; CURETTAGE; DIARRHEA; DRUG FATALITY; DRUG INDICATION; DRUG MECHANISM; DRUG METABOLISM; DRUG STRUCTURE; DRUG SYNTHESIS; ECTOPIC PREGNANCY; ENDOMETRIOSIS; FETUS DEATH; GASTROINTESTINAL SYMPTOM; HUMAN; HYPOGLYCEMIA; INDUCED ABORTION; LABOR INDUCTION; LEIOMYOMA; LIVER FUNCTION TEST; LOW DRUG DOSE; MEDICAL ABORTION; MISSED ABORTION; NAUSEA; NONHUMAN; PREGNANCY TERMINATION; PREMATURE LABOR; PROLONGED PREGNANCY; RECOMMENDED DRUG DOSE; REVIEW; SEPSIS; SIDE EFFECT; SINGLE DRUG DOSE; SPONTANEOUS ABORTION; STRUCTURE ACTIVITY RELATION; UTERINE CERVIX RIPENING; UTERUS BLEEDING; UTERUS CONTRACTION; UTERUS MYOMA; VOMITING;

FEMALE; HUMANS; PREGNANCY; RECEPTORS, PROGESTERONE; REPRODUCTIVE MEDICINE;

EID: 54349115902     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656566.9.14.2459     Document Type: Review

References (100)

1. Giangrande PH, McDonnell DP. The A and B isoforms of the human progesterone receptor: two functionally different transcription factors encoded by a single gene. Recent Prog Horm Res 1999;54:291-313
2. Dijkema R, Schoonen WGEJ, Teuwen R, et al. Human progesterone receptor A and B isoforms in CHO cells. 1. Stable transfection of receptor and receptor-responsive reporter genes: transcription modulation by (anti) progestagens. J Steroid Bio Chem Mol Biol 1998;64:147-56
3. Gronemeijer H, Meyer M-E, Bocquel M-TH, et al. Progestin receptors: isoforms and antihormone action. J Steroid Biochem 1991;40:271-8
4. Spitz IM, Bardin CW. Clinical pharmacology of RU 486 - an antiprogestin and antiglucocorticoid. Contraception 1993;48:403-518
5. Ilenchuck TT, Walters MR. Rat uterine progesterone receptor analyzed by tritiated R-5020 photoaffinity labelling; evidence that the A and B subunits are not equimolar. Endocrinology 1987;120:1449-56
6. Christensen K, Estes P, Onate S, et al. Characterization and functional properties of the A and B forms of human progesterone receptors synthesized in a baculovirus system. Mol Endocrinol 1990;24:1465-73
7. Conneely OM, Mulac-Jerevic B, Lydon JP. Progesterone-dependent regulation of female reproductive activity by two distinct progesterone receptor isoforms. Steroids 2003;68:771-8
8. Chabbert-Buffet N, Meduri G, Bouchard P, Spitz IM. Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum Reprod Update 2005;11:293-307
9. Spitz IM, Chwalisz K. Progesterone receptor modulators and progesterone antagonists in women's health. Steroids 2000;65:807-15
10. Benagiano G, Farris M, Primiero FM. Clinical profile of contraceptive progestins. Eur J Contracept Reprod Healthcare 2004;9:182-93
11. Spitz IM. Progesterone antagonists and progesterone receptor modulators: an overview. Steroids 2003;68:981-93
12. Klein-Hitpass L, Cato AC, Henderson D, Ryffel GU. Two types of antiprogestins identified by their differential action in transcriptionally active extracts from T47D cells. Nucleic Acids Res 1991;19:1227-34
13. Liu Z, Auboeuf D, Wang J, et al. Coactivator/Corepressor ratios modulate PR-mediated transcription by the selective receptor modulator RU486. Proc Natl Acad Sci USA 2002;99:7940-4
14. Elger W, Bartley J, Schneider B, et al. Endocrine pharmacological characterization of progesterone antagonists and progesterone receptor modulators with respect to PR-agonistic and antagonistic activity. Steroids 2000;65:713-23
15. Chwalisz K, Perez MC, Demanno D, et al. Selective progesterone receptor modulation: development and use in the treatment of leiomyomata and endometriosis. Endocr Rev 2005;26:423-38
16. Baulieu EE. RU 486 - a decade on, today and tomorrow. In: Donaldson MS, Dorflinger L, Brown SS, et al, editors. Clinical applications of mifespristone RU 486 and other antiprogestins. Washington: National Academy Press; 1993. p. 71-119
17. Spitz IM, Croxatto HB, Robbins A. Antiprogestins: mechanism of action and contraceptive potential. Annu Rev Pharmacol Toxicol 1996;36:47-81
18. Mahajan DK, London SN. Mifepristone (RU486): a review. Fertil Steril 1997;68:967-76
19. Bygdeman M, Swahn ML. Progesterone receptor blockage. Effect on uterine contractility and early pregnancy. Contraception 1985;32:45-51
20. Baird DT. Mode of action of medical methods of abortion. J Am Med Womens Assoc 2000;55(3 Suppl):121-6
21. Cameron ST, Glasier AF, Narvekar N, et al. Effects of onapristone on postmenopausal endometrium. Steroids 2003;68:1053-9
22. Cameron ST, Critchley HO, Thong KJ, et al. Effects of daily low dose mifepristone on endometrial maturation and proliferation. Hum Reprod 1996;11:2518-26
23. Blithe DL, Niemanm LK, Blye RP, et al. Development of the selective progesterone receptor modulator CDB-2914 for clinical indications. Steroids 2003;68:1013-7
24. Attardi BJ, Burgenson J, Hild SA, et al. CDB-4124 and its putative monodemethylated metabolite, CDB-4453, are potent antiprogestins with reduced antiglucocorticoid activity: in vitro comparison to mifepristone and CDB-2914. Mol Cell Endocrinol 2002;188:111-23
25. Kloostenboer HJ, Deckers GH, De Gooyer ME, et al. Pharmacological properties of a new selective antigestagen: ORG 3368. Ann NY Acad Sci 1995;761:192-201
26. Verbost PM, Kloosterboer HI, Schoonen WGJE, et al. Differential antiprogestin potencies: ORG 31710 vs ORG 33628 for menstrual induction in desogestrel-treated monkeys. In: The Endocrine Society: Program and Abstracts of the 80th Annual Meeting; Bethesda: The Endocrine Society; 1998. p. 256
27. Negro-Vilar A. New progestins and potential actions. J Soc Gynecol Invest 2000;7:S53-4
28. Philibert D, Deraedt R, Teutsch G. RU 38486: a potent antiglucocorticoid in vivo. In: Proceedings of the Seventh International Congress of Pharmacology. Tokyo, Japan; 1981
29. Ulmann A, Teutsch G, Philibert D. RU 486. Sci Am 1990;262:42-8
30. Herrmann W, Wyss R, Riondel A, et al. The effects of an antiprogesterone steroid in women: interruption of the menstrual cycle and of early pregnancy. CR Acad Sci Paris 1982;294:933-8
31. Donaldson MS, Dorflinger L, Brown SS, Benet LS, editors. Clinical applications of mifespristone RU 486 and other antiprogestins. Washington: National Academy Press; 1993
32. Van Look PFA, Von Hertzen H. Antiprogestins: perspective from a global research. In: Donaldson MS, Dorflinger L, Brown SS, Benet LS, editors, Clinical applications of mifespristone RU 486 and other antiprogestins. Washington: National Academy Press; 1993. p. 253-77
33. Beier HM, Spitz IM. Progesterone antagonists in reproductive medicine and oncology. Hum Reprod 1994;9(Suppl 1)
34. Benagiano G, Primiero FM. The potential use of antiprogestins in gynaecological disorders. In: Motta M, Serio M, editors, Sex hormones and antihormones in endocrine dependent pathology: basic and clinical aspects. Amsterdam: Elsevier Science; 1994. p. 391-9
35. Agarwal MK. Antihormonal steroids revisited. Drugs Future 1995;20:903-10
36. Tang OS, Ho PC. Clinical applications of mifepristone. Gynecol Endocrinol 2006;22:655-9
37. Chwalisz K. The use of progesterone antagonists for cervical ripening and as an adjunct to labour and delivery. Hum Reprod 1994;9(Suppl 1):131-61
38. Royal College of Obstetricians and Gynaecologists Study Group. Recommendations from the 33rd RCOG Study Group. In: Grudzinkas JG, O'Brien PMS, editors, Problems in early pregnancy: advances in diagnosis and management. London: RCOG Press; 1997. p. 327-31
39. Wagaarachchi PT, Ashok PW, Narvekar N, et al. Medical management of early fetal demise using a combination of mifepristone and misoprostol. Hum Reprod 2001;16:1849-53
40. Hemminki E. Treatment of miscarriage: current practice and rationale. Obstet Gynecol 1998;179:397-8
41. Chen BA, Creinin MD. Contemporary management of early pregnancy failure. Clin Obstet Gynecol 2007;50:67-88
42. Nielsen S, Hahlin M. Expectant management of first-trimester spontaneous abortion. Lancet 1995;345:84-6
43. Jurkovic D, Ross JA, Nicolaides KH. Expectant management of missed miscarriage. Br J Obstet Gynaecol 1998;105:670-1
44. Bagratee JS, Khullar V, Regan L, et al. Randomised-controlled trial comparing medical and expectant management of first trimester miscarriage. Hum Reprod 2004;19:266-71
45. El-Rafeay H, Hinshaw K, Henshaw R, et al. Medical management of missed abortion and anembryonic pregnancy. BMJ 1992;305:1399-403
46. Lelaidier C, Baton-Saint-Mleux C, Fernandez H, et al. Mifepristone (RU486) induces embryo expulsion in first trimester non-developing pregnancies: a prospective randomized trial. Hum Reprod 1993;8:492-5
47. Schaff EA, Fielding SL, Eisinger S. Stadalius L. Mifepristone and misoprostol for early abortion when no gestational sac is present. Contraception 2001;63:251-4
48. Wagaarachchi PT, Ashok PW, Smith NC, Templeton A. Medical management of early fetal demise using sublingual misoprostol. Br J Obstet Gynaecol 2002;109:462-5
49. Gronlund A, Gronlund L, Clevin L, et al. 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 2002;81:1060-5
50. Sotiriadis A, Makrydimas G, Papatheodorou S, Ioannidis JP. Expectant, medical, or surgical management of first-trimester miscarriage: a meta-analysis. Obstet Gynecol 2005;105:1104-13
51. Hughes J, Ryan M, Hinshaw K, et al. The costs of treating miscarriage: a comparison of medical and surgical management. Br J Obstet Gynaecol 1996;103:1217-21
52. Fletcher HM, Wharfe G, Simeon D, et al. Induction of labour with intravaginal misoprostol versus dinoprostone in intrauterine death: a retrospective study. J Obstet Gynaecol 1996;16:155-8
53. Bugalho A, Bique C, Machungo F, Faundes A. Induction of labour with intravaginal misoprostol in intrauterine fetal death. Am J Obstet Gynecol 1994;171:538-41
54. Cabrol D, Bouvier D'yvoire M, Mermet E, et al. Induction of labour with mifepristone after intrauterine fetal death. Lancet 1985;2:1019
55. Cabrol D, Dubois C, Cronje H, et al. Induction of labor with mifepristone (RU486) in intrauterine fetal death. Am J Obstet Gynecol 1990;163:540-2
56. Vayrynen W, Heikinheimo O, Nuutila M. Misoprostol-only versus mifepristone plus misoprostol in induction of labour following intrauterine fetal death. Acta Obstet Gynecol Scand 2007;86:701-5
57. Wagaarachchi PT, Ashok PW, Narvekar N, et al. Medical management of late intrauterine death using a combination of mifepristone and misoprostol. Br J Obstet Gynaecol 2002;109:443-7
58. Neilson JP, Hickey M, Vazquez J. Medical treatment for early fetal death (less than 24 weeks). Cochrane Database Syst Rev 2006;3:CD002253
59. Neilson JP. Mifepristone fist induction of labour. Cochrane Database System Rev 2000;4:CD002865
60. Elliott CL, Brennand JE, Calder AA. The effects of mifepristone on cervical ripening and labor induction in primigravidae. Obstet Gynecol 1998;92:804-9
61. 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;97:406-11
62. Wing DA, Fassett MJ, Mishell DR. Mifepristone fist preinduction of cervical ripening beyond 41 weeks' gestation: a randomized controlled trial. Obstet Gynecol 2000;96:543-8
63. Fassett MJ, Wing DA. Uterine activity after oral mifepristone administration in human pregnancies beyond 41 weeks' gestation. Gynecol Obstet Invest 2008;62:112-5
64. Paris FX, Henry-Suchet J, Tesquier L, et al. Effect of an antiprogesterone (RU 486) on extra-uterine pregnancy. Rev Fr Gynecol Obstet 1986;81:33-5
65. Das C, Catt KJ. Antifertility actions of the progesterone antagonist RU 486 include direct inhibition of placental hormone secretion. Lancet 1987;2(8559):599-601
66. Wolf JP, Hsiu JG. Anderson TL, et al. Noncompetitive antiestrogenic effect of RU 486 in blocking the estrogen-stimulated luteinizing hormone surge and the proliferative action of estradiol on endometrium in castrate monkeys. Fertil Steril 1989;52:1055-060
67. Sowter MC, Farquhar CM. Ectopic pregnancy: an update. Curr Opin Obstet Gynecol 2004;16:289-93
68. Aubeny E, Peyron R, Larquier-Turpin C, 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
69. Jain JK, Dutton C, Harwood B, et al. A prospective randomized, double-blinded, placebo-controlled trial comparing mifepristone and vaginal misoprostol to vaginal misoprostol alone for elective termination of early pregnancy. Hum Reprod 2002;17:1477-82
70. Von Hertzen H, Honkanen H, Piaggio G, et al. For the world health organisation research group on post-ovulatory methods for fertility regulation: WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion. I. Efficacy. Br J Obstet Gynaecol 2003;110:808-18
71. Honkanen H, Piaggio G, Von Hertzen H, et al. WHO multinational study of three misoprostol regimens after mifepristone for early medical abortion. II. Side effects and women's perceptions. Br J Obstet Gynaecol 2004;111:715-25
72. Guest J, Chien PF, Thomson MA, Kosseim ML. Randomised controlled trial comparing the efficacy of same-day administration of mifepristone and misoprostol for termination of pregnancy with the standard 36 to 48 hour protocol. Br J Obstet Gynaecol 2007;114:207-15
73. Heikinheimo O, Leminen R, Suhonen S. Termination of early pregnancy using flexible, low-dose mifepristone-misoprostol regimens. Contraception 2007;76:456-60
74. Van Bogaert LJ, Sedibe TM. Efficacy of a single misoprostol regimen in the first and second trimester termination of pregnancy. J Obstet Gynaecol 2007;27:510-2
75. Zieman M, Fong SK, Benowitz NL, et al. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet Gynecol 1997;90:88-92
76. Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med 1998;338:1241-7
77. Ashok PW, Flett GM, Templeton A. Mifepristone versus vaginally administered misoprostol for cervical priming before first-trimester termination of pregnancy: a randomized, controlled study. Am J Obstet Gynecol 2000;183:998-1002
78. Bartley J, Tong S, Everington D, Baird DT. Parity is a major determinant of success rate in medical abortion: a retrospective analysis of 3161 consecutive cases of early medical abortion treated with reduced doses of mifepristone and vaginal gemeprost. Contraception 2000;62:297-303
79. World Health Organisation, Task Force On Postovulatory Methods Of Fertility Regulation: Termination of pregnancy with reduced doses of mifepristone. BMJ 1993;307:532-7
80. Christin-Maitre S, Bouchard P, Spitz IM. Medical termination of pregnancy. N Engl J Med 2000;342:946-56
81. 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;10:1521-7
82. Ashok PW, Penney GC, Flett GM, Templeton A. An effective regimen for early medical abortion: a report of 2000 consecutive cases. Hum Reprod 1998;13:2962-5
83. Parashar P, Iversen OE, Midboe G, et al. Medical abortion in the first trimester: the use of serum hCG and endometrial thickness as markers of completeness. Eur J Contracept Reproduct Health Care 2007;16:1-6
84. Kulier R, Giilmezoglu AM, Hofmeyr GJ, et al. Medical methods for first trimester abortion. Cochrane Database Syst Rev 2004;3:CD001328
85. Sinave C, Le Templier G, Bluin D, et al. Toxic shock syndrome due to Clostridium sordellii: a dramatic postpartum and postabortion disease. Clin Infect Dis 2002;35:1441-3
86. ACOG Practice Bulletin: medical management of abortion. Obstet Gynecol 2005;106:871-82
87. Creinin M, Blumenthal P, Shulman L. Mifepristone-Misoprostol medical abortion mortality. Med Gen Med 2006;8:26
88. Puri CP, Patil RK, Elger WA, Pongubala JM. Effects of progesterone antagonist ZK 98.299 on early pregnancy and foetal outcome in bonnet monkeys. Contraception 1990;41:197-205
89. Ashok PW, Kidd A, Flett GMM, et al. A randomized comparison of medical abortion and surgical vacuum aspiration at 10 - 13 weeks gestation. Hum Reprod 2002;17:92-8
90. Rodger MW, Baird DT. Pretreatment with mifepristone (RU 486) reduces interval between prostaglandin administration and expulsion in second trimester abortion. Br J Obstet Gynaecol 1990;97:41-5
91. Gouk EV, Lincoln K, Khair A, et al. Medical termination of pregnancy at 63-83 days gestation. Br J Obstet Gynaecol 1999;106:535-9
92. Hamoda H, Ashok PW, Flett GM, Templeton A. Medical abortion at 64 to 91 days of gestation: a review of 483 consecutive cases. Am J Obstet Gynecol 2003;188:1315-9
93. Bracken H, Ngoc NT, Schaff E, et al. Mifepristone followed in 24 hours to 48 hours by misoprostol for late first-trimester abortion. Obstet Gynecol 2007;109:895-901
94. Hamoda H, Ashok PW, Flett GMM, Templeton A. A randomised trial of mifepristone in combination with misoprostol administered sublingually or vaginally for medical abortion at 13-20 weeks gestation. Hum Reprod 2003;20:2348-54
95. Nilas L, Glavind-Kristensen M, Veihorg T, Knudsen WI. One or two day mifepristone-misoprostol interval for second trimester abortion. Acta Obstet Gynecol Scand 2007;86:1117-21
96. Kapp N, Borgatta L, Stubblefield P, et al. Mifepristone in second-trimester medical abortion: a randomized controlled trial. Obstet Gynecol 2007;110:1304-10
97. Creinin MD, Schreiber CA, Bednarek P, et al. Medical Abortion at the Same Time (MAST) Study trial group. Mifepristone and misoprostol administered simultaneously versus 24 hours apart for abortion: a randomized controlled trial. Obstet Gynecol 2007;109:885-94
98. Ho PC, Blumenthal PD, Gemzell-Danielsson SK, et al. Misoprostol for the termination of pregnancy a live foetus at 13 to 26 weeks. Int J Obstet Gynecol 2007;99:S178-81
99. Lohr P, Hayes J, Gemzell-Danielsson K. Surgical versus medical methods for second trimester induced abortion. Cochrane Database Syst Rev 2008;1:CD006714
100. Clark WH, Gold M, Grossman D, Winikoff B. Can mifepristone medical abortion be simplified? A review of the evidence and questions for future research. Contraception 2007;75:245-50