Progesterone receptor antagonists and selective progesterone receptor modulators: proven and potential clinical applications

References

• Smith CL, O’Malley BW. Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr. Rev.25, 45–71 (2004).
   PubMed Web of Science ®Google Scholar
• Wagner BL, Norris JD, Knotts TA, Weigel NL, McDonnell DP. 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, 1369–1378 (1998).
   PubMed Web of Science ®Google Scholar
• Bray JD, Grygielko ET, Sulpizio AC et al. Asoprisnil, a selective progesterone receptor modulator, displays a distinct profile in PR-mediated assays, and the ability to recruit both coactivators and corepressors may explain its failure to demonstrate antiestrogenic activity on eutopic and ectopic rat uterine tissue. Endocrine Society Meeting. Boston, MA, USA, 24–27 June 2006 (Abstract 1–519).
   Google Scholar
• Melvin VS, Perez MC, Chwalisz K, Edwards DP. Mechanism of action of the selective progesterone receptor modulator, asoprisnil. Endocrine Society Meeting. San Diego, CA, USA, 4–7 June 2005.
   Google Scholar
• Kastner P, Krust A, Turcotte B et al. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J.9, 1603–1614 (1990).
   PubMed Web of Science ®Google Scholar
• 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.54, 291–313 (1999).
   PubMedGoogle Scholar
• Wei LL, Hawkins P, Baker C et al. An amino-terminal truncated progesterone receptor isoform, PRc, enhances progestin-induced transcriptional activity. Mol. Endocrinol.10, 1379–1387 (1996).
   PubMed Web of Science ®Google Scholar
• Mulac-Jericevic B, Conneely OM. Reproductive tissue selective actions of progesterone receptors. Reproduction128, 139–146 (2004).
   PubMed Web of Science ®Google Scholar
• Fernandez-Valdivia R, Mukherjee A, Mulac-Jericevic B et al. Revealing progesterone’s role in uterine and mammary gland biology: insights from the mouse. Semin. Reprod. Med.23, 22–37 (2005).
   PubMed Web of Science ®Google Scholar
• Condon JC, Hardy DB, Kovaric K, Mendelson CR. Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-κB may contribute to the onset of labor through inhibition of PR function. Mol. Endocrinol.2, 764–775 (2006).
   Google Scholar
• McPhail MK. The assay of progestin. J. Physiol.83, 145–156 (1934).
   PubMedGoogle Scholar
• 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. Steroids65, 713–723 (2000).
   PubMed Web of Science ®Google Scholar
• Philibert D. RU38486: an original multifaceted antihormone in vivo. In: Adrenal Steroid Antagonism. Agarwal M (Ed.), Walter de Gruyter and Co., Berlin, Germany 77–101 (1984).
   Google Scholar
• DeManno D, Elger W, Garg R et al. Asoprisnil (J867): a selective progesterone receptor modulator for gynecological therapy. Steroids68, 1019–1032 (2003).
   PubMed Web of Science ®Google Scholar
• World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation. The use of mifepristone (RU486) for cervical preparation in first trimester pregnancy termination by vacuum aspiration. Br. J. Obstet. Gynaecol.97, 260–266 (1990).
   PubMedGoogle Scholar
• Chwalisz K, Garg R, Brenner RM, Schubert G, Elger W. Selective progesterone receptor modulators (SPRMs): a novel therapeutic concept in endometriosis. Ann. NY Acad. Sci.955, 373–388 (2002).
   PubMed Web of Science ®Google Scholar
• Hodgen GD, van Uem JF, Chillik CF et al. Non-competitive anti-oestrogenic activity of progesterone antagonists in primate models. Hum. Reprod.9(Suppl. 1), 77–81 (1994).
   PubMed Web of Science ®Google Scholar
• Slayden OD, Zelinski Wooten MB, Chwalisz K, Stouffer RL, Brenner RM. 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, 269–277 (1998).
   PubMed Web of Science ®Google Scholar
• Slayden OD, Brenner RM. RU 486 action after estrogen priming in the endometrium and oviducts of rhesus monkeys (Macaca mulatta). J. Clin. Endocrinol. Metab.78, 440–448 (1994).
   PubMed Web of Science ®Google Scholar
• DeHart RM, Morehead MS. Mifepristone. Ann. Pharmacother.35, 707–719 (2001).
   PubMed Web of Science ®Google Scholar
• Sitruk-Ware R. Approval of mifepristone (RU 486) in Europe. Zentralbl Gynakol.122, 241–247 (2000).
   PubMedGoogle Scholar
• Fiala C, Gemzel-Danielsson K. Review of medical abortion using mifepristone in combination with a prostaglandin analogue. Contraception74, 66–86 (2006).
   PubMed Web of Science ®Google Scholar
• Fischer M, Bhatnagar J, Guarner J et al. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N. Engl. J. Med.353, 2352–2360 (2005).
   PubMed Web of Science ®Google Scholar
• Sinave C, Le Templier G, Blouin D, Leveille F, Deland E. Toxic shock syndrome due to Clostridium sordellii: a dramatic postpartum and postabortion disease. Clin. Infect. Dis.35, 1441–1443 (2002).
   PubMed Web of Science ®Google Scholar
• Sitruk-Ware R. Mifepristone and misoprostol sequential regimen side effects, complications and safety. Contraception74, 48–55 (2006).
   PubMed Web of Science ®Google Scholar
• Bartlett JG, Onderdonk AB, Drude E et al. Quantitative bacteriology of the vaginal flora. J. Infect. Dis.136, 271–277 (1977).
   PubMed Web of Science ®Google Scholar
• Holtz F, Mauch EW. Gas gangrene of uterus: survival following hysterectomy. Obstet. Gynecol.19, 545–548 (1962).
   PubMed Web of Science ®Google Scholar
• Miech RP. Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii. Ann. Pharmacother.39, 1483–1488 (2005).
   PubMed Web of Science ®Google Scholar
• Webster JI, Tonelli L, Sternberg EM. Neuroendocrine regulation of immunity. Ann. Rev. Immunol.20, 125–163 (2002).
   PubMed Web of Science ®Google Scholar
• Heikinheimo O, Raivio T, Honkanen H, Ranta S, Janne OA. Termination of pregnancy with mifepristone and prostaglandin suppresses transiently circulating glucocorticoid bioactivity. J. Clin. Endocrinol. Metab.88, 323–326 (2003).
   PubMed Web of Science ®Google Scholar
• van Voorhis BJ, Anderson DJ, Hill JA. The effects of RU 486 on immune function and steroid-induced immunosuppression in vitro. J. Clin. Endocrinol. Metab.69, 1195–1199 (1989).
   PubMed Web of Science ®Google Scholar
• Laue L, Lotze MT, Chrousos GP et al. Effect of chronic treatment with the glucocorticoid antagonist RU 486 in man: toxicity, immunological, and hormonal aspects. J. Clin. Endocrinol. Metab.71, 1474–1480 (1990).
   PubMed Web of Science ®Google Scholar
• Laue L, Kawai S, Brandon DD et al. Receptor-mediated effects of glucocorticoids on inflammation: enhancement of the inflammatory response with a glucocorticoid antagonist. J. Steroid Biochem.29, 591–598 (1988).
   PubMedGoogle Scholar
• Spitz IM, Grunberg S, Chabbert-Buffet N et al. Management of patients receiving long term treatment with mifepristone. Fertil. Steril.84, 1719–1726 (2005).
   PubMed Web of Science ®Google Scholar
• 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, 601–605 (1992).
   PubMed Web of Science ®Google Scholar
• McDonald MD. Surveillance for disease and sources of infection: initiatives at the federal level and international. Emerging Clostridial Disease Workshop. Atlanta, GA, USA, 11 May 2006.
   Google Scholar
• Baulieu EE. Letter: Deaths from Clostridium sordellii after medical abortion. N. Engl. J. Med.354, 1645–1647 (2006).
   PubMed Web of Science ®Google Scholar
• Greene MF. Fatal infections associated with mifepristone-induced abortion. N. Engl. J. Med.353, 2317–2318 (2005).
   PubMed Web of Science ®Google Scholar
• Bartlett LA, Berg CJ, Shulman HB et al. Risk factors for legal induced abortion-related mortality in the United States. Obstet. Gynecol.103, 729–737 (2004).
   PubMed Web of Science ®Google Scholar
• Christin-Maitre S, Bouchard P, Spitz IM. Medical termination of pregnancy. N. Engl. J. Med.342, 946–956 (2000).
   PubMed Web of Science ®Google Scholar
• Tang OS, Schweer H, Seyberth HW, Lee SWH, Ho PC. Pharmacokinetics of different routes of administration of misoprostol. Hum. Reprod.17, 332–336 (2002).
   PubMed Web of Science ®Google Scholar
• Tang OS, Chan CC, Ng EH, Lee SW, Ho PC. A prospective, randomized, placebo-controlled trial on the use of mifepristone with sublingual or vaginal misoprostol for medical abortions of less than 9 weeks gestation. Hum. Reprod.18, 2315–2318 (2003).
   PubMed Web of Science ®Google Scholar
• 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. Br. J. Obstet. Gynaecol.108, 469–473 (2001).
   Google Scholar
• Schaff EA, Fielding SL, Westhoff C et al. Vaginal misoprostol administered 1, 2, or 3 days after mifepristone for early medical abortion: a randomized trial. JAMA284, 1948–1953 (2000).
   PubMed Web of Science ®Google Scholar
• Pymar HC, Creinin MD, Schwartz JL. Mifepristone followed on the same day by vaginal misoprostol for early abortion. Contraception64, 87–92 (2001).
   PubMed Web of Science ®Google Scholar
• Fox MC, Creinin MD, Harwood B. Mifepristone and vaginal misoprostol on the same day for abortion from 50 to 63 days’ gestation. Contraception66, 225–229 (2002).
   PubMed Web of Science ®Google Scholar
• Creinin MD, Fox MC, Teal S et al. A randomized comparison of misoprostol 6 to 8 hours versus 24 hours after mifepristone for abortion. Obstet. Gynecol.103, 851–859 (2004).
   PubMed Web of Science ®Google Scholar
• Murthy AS, Creinin MD, Harwood B, Schreiber C. A pilot study of mifepristone and misoprostol administered at the same time for abortion up to 49 days gestation. Contraception71, 333–336 (2005).
   PubMed Web of Science ®Google Scholar
• Ashok PW, Templeton A. Nonsurgical mid-trimester termination of pregnancy: a review of 500 consecutive cases. Br. J. Obstet. Gynaecol.106, 706–710 (1999).
   PubMedGoogle Scholar
• Bartley J, Baird DT. A randomised study of misoprostol and gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy. Br. J. Obstet. Gynaecol.109, 1290–1294 (2002).
   Google Scholar
• Ngai SW, Tang OS, Ho PC. Randomized comparison of vaginal (200 microg every 3 h) and oral (400 microg every 3 h) misoprostol when combined with mifepristone in termination of second trimester pregnancy. Hum. Reprod.15, 2205–2208 (2000).
   PubMed Web of Science ®Google Scholar
• Cabrol D, Dubois C, Cronje H et al. Induction of labor with mifepristone (RU 486) in intrauterine fetal death. Am. J. Obstet. Gynecol.163, 540–542 (1990).
   PubMed Web of Science ®Google Scholar
• Wagaarachchi PT, Ashok PW, Narvekar NN, Smith NC, Templeton A. Medical management of late intrauterine death using a combination of mifepristone and misoprostol. Br. J. Obstet. Gynaecol.109, 443–447 (2002).
   Google Scholar
• Lelaidier C, Baton Saint Mleux C, Fernandez H, Bourget P, Frydman R. Mifepristone (RU 486) induces embryo expulsion in first trimester non-developing pregnancies: a prospective randomized trial. Hum. Reprod.8, 492–495 (1993).
   PubMed Web of Science ®Google Scholar
• Schaff EA, Fielding SL, Eisinger S, Stadalius L. Mifepristone and misoprostol for early abortion when no gestational sac is present. Contraception63, 251–254 (2001).
   PubMed Web of Science ®Google Scholar
• Hughes J, Ryan M, Hinshaw K et al. The costs of treating miscarriage: a comparison of medical and surgical management. Br. J. Obstet. Gynaecol.103, 1217–1221 (1996).
   PubMedGoogle Scholar
• el Refaey H, Hinshaw K, Henshaw R, Smith N, Templeton A. Medical management of missed abortion and anembryonic pregnancy. Br. Med J.305, 1399 (1992).
   PubMed Web of Science ®Google Scholar
• Wagaarachchi PT, Ashok PW, Narvekar N, Smith NC, Templeton A. Medical management of early fetal demise using a combination of mifepristone and misoprostol. Hum. Reprod.16, 1849–1853 (2001).
   PubMed Web of Science ®Google Scholar
• Chia KV, Ogbo VI. Medical termination of missed abortion. J. Obstet. Gynaecol.22, 184–186 (2002).
   PubMedGoogle Scholar
• Coughlin LB, Roberts D, Haddad NG, Long A. Medical management of first trimester miscarriage (blighted ovum and missed abortion): is it effective? J. Obstet. Gynaecol.24, 69–71 (2004).
   PubMedGoogle Scholar
• Wagaarachchi PT, Ashok PW, Smith NC, Templeton A. Medical management of early fetal demise using sublingual misoprostol. Br. J. Obstet. Gynaecol.109, 462–465 (2002).
   Google Scholar
• Messinis IE, Krishnan M, Kazem R, Khadilkar S, Templeton AA. Effect of mifepristone on folliculogenesis in women treated with recombinant FSH. Clin. Endocrinol. (Oxf.)46, 309–314 (1997).
   PubMed Web of Science ®Google Scholar
• Escudero EL, Boerrigter PJ, Bennink HJ et al. Mifepristone is an effective oral alternative for the prevention of premature luteinizing hormone surges and/or premature luteinization in women undergoing controlled ovarian hyperstimulation for in vitro fertilization. J. Clin. Endocrinol. Metab.90, 2081–2088 (2005).
   PubMed Web of Science ®Google Scholar
• Hegele Hartung C, Mootz U, Beier HM. Luteal control of endometrial receptivity and its modification by progesterone antagonists. Endocrinology131, 2446–2460 (1992).
   PubMed Web of Science ®Google Scholar
• Paulson RJ, Sauer MV, Lobo RA. Potential enhancement of endometrial receptivity in cycles using controlled ovarian hyperstimulation with antiprogestins: a hypothesis. Fertil. Steril.67, 321–325 (1997).
   PubMed Web of Science ®Google Scholar
• Cekan S, Aedo AR, Segersteen E et al. Levels of the antiprogestin RU 486 and its metabolites in human blood and follicular fluid following oral administration of a single dose. Hum. Reprod.4, 131–135 (1989).
   PubMed Web of Science ®Google Scholar
• Perdu M, Camus E, Rozenberg P et al. Treating ectopic pregnancy with the combination of mifepristone and methotrexate: a Phase II nonrandomized study. Am. J. Obstet. Gynecol.179, 640–643 (1998).
   PubMed Web of Science ®Google Scholar
• Gazvani MR, Baruah DN, Alfirevic Z, Emery SJ. Mifepristone in combination with methotrexate for the medical treatment of tubal pregnancy: a randomized, controlled trial. Hum. Reprod.13, 1987–1990 (1998).
   PubMed Web of Science ®Google Scholar
• Rozenberg P, Chevret S, Camus E et al. Medical treatment of ectopic pregnancies: a randomized clinical trial comparing methotrexate–mifepristone and methotrexate–placebo. Hum. Reprod.18, 1802–1808 (2003).
   PubMed Web of Science ®Google Scholar
• Ben-Chetrit A, Eldar-Geva T, Lindenberg T et al. Mifepristone does not induce cervical softening in non-pregnant women. Hum. Reprod.19, 2372–2376 (2004).
   PubMed Web of Science ®Google Scholar
• 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, 308–314 (1995).
   PubMed Web of Science ®Google Scholar
• Xiao B, von Hertzen H, Zhao H, Piaggio G. Menstrual induction with mifepristone and misoprostol. Contraception68, 489–494 (2003).
   PubMed Web of Science ®Google Scholar
• Neilson JP. Mifepristone for induction of labour. Cochrane Database Syst. Rev.CD002865 (2000).
   Google Scholar
• Giacalone PL, Targosz V, Laffargue F, Boog G, Faure JM. Cervical ripening with mifepristone before labor induction: a randomized study. Obstet. Gynecol.92, 487–492 (1998).
   PubMed Web of Science ®Google Scholar
• Wing DA, Fassett MJ, Mishell DR. Mifepristone for preinduction cervical ripening beyond 41 weeks’ gestation: a randomized controlled trial. Obstet. Gynecol.96, 543–548 (2000).
   PubMed Web of Science ®Google Scholar
• Stenlund PM, Ekman G, Aedo AR, Bygdeman M. Induction of labor with mifepristone – a randomized, double-blind study versus placebo. Acta Obstet. Gynecol. Scand.78, 793–798 (1999).
   PubMed Web of Science ®Google Scholar
• Lelaidier C, Baton C, Benifla JL et al. Mifepristone for labour induction after previous caesarean section. Br. J. Obstet. Gynaecol.101, 501–503 (1994).
   PubMedGoogle Scholar
• Berkane N, Verstraete L, Uzan S, Boog G, Maria B. Use of mifepristone to ripen the cervix and induce labor in term pregnancies. Am. J. Obstet. Gynecol.192, 114–120 (2005).
   PubMed Web of Science ®Google Scholar
• Elliott CL, Brennand JE, Calder AA. The effects of mifepristone on cervical ripening and labor induction in primigravidae. Obstet. Gynecol.92, 804–809 (1998).
   PubMed Web of Science ®Google Scholar
• Giacalone PL, Daures JP, Faure JM et al. The effects of mifepristone on uterine sensitivity to oxytocin and on fetal heart rate patterns. Eur. J. Obstet. Gynecol. Reprod. Biol.97, 30–34 (2001).
   PubMed Web of Science ®Google Scholar
• Hill NC, Selinger M, Ferguson J, MacKenzie IZ. The placental transfer of mifepristone (RU 486) during the second trimester and its influence upon maternal and fetal steroid concentrations. Br. J. Obstet. Gynaecol.97, 406–411 (1990).
   PubMedGoogle Scholar
• Goldberg AB, Greenberg MB, Darney PD. Misoprostol and pregnancy. N. Engl. J. Med.344, 38–47 (2001).
   PubMed Web of Science ®Google Scholar
• 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.81, 1060–1065 (2002).
   PubMed Web of Science ®Google Scholar
• Hale RW, Zinberg S. Use of misoprostol in pregnancy. N. Engl. J. Med.344, 59–60 (2001).
   PubMed Web of Science ®Google Scholar
• Weeks A, Alfirevic Z. Oral misoprostol administration for labor induction. Clin. Obstet. Gynecol.49, 658–671 (2006).
   PubMed Web of Science ®Google Scholar
• Choksuchat C, Cheewadhanaraks S, Getpook C, Wootipoom V, Dhanavoravibul K. Misoprostol for cervical ripening in non-pregnant women: a randomized double-blind controlled trial of oral versus vaginal regimens. Hum. Reprod.21, 2167–2170 (2006).
   PubMed Web of Science ®Google Scholar
• Baird DT, Brown A, Critchley HO et al. Effect of long-term treatment with low-dose mifepristone on the endometrium. Hum. Reprod.18, 61–68 (2003).
   PubMed Web of Science ®Google Scholar
• Spitz IM, Chwalisz K. Progesterone receptor modulators and progesterone antagonists in women’s health. Steroids65, 807–815 (2000).
   PubMed Web of Science ®Google Scholar
• Neulen J, Williams RF, Breckwoldt M et al. 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, 1533–1537 (1996).
   PubMed Web of Science ®Google Scholar
• Brenner RM, Slayden OD, Critchley HO. Anti-proliferative effects of progesterone antagonists in the primate endometrium: a potential role for the androgen receptor. Reproduction124, 167–172 (2002).
   PubMed Web of Science ®Google Scholar
• Slayden OD, Carroll R, Mah K, Brenner RM. Exogenous androgen blocks endometrial growth in primates: relevance to the antiproliferative effects of progesterone antagonists. Society of Gynecologic Investigation 53rd Annual Meeting. Toronto, Ontario, Canada, 22–25 March 2006 (Abstract 851).
   Google Scholar
• Slayden OD, Brenner RM. Flutamide counteracts the antiproliferative effects of antiprogestins in the primate endometrium. J. Clin. Endocrinol. Metab.88, 946–949 (2003).
   PubMed Web of Science ®Google Scholar
• McDonnell DP, Goldman ME. RU486 exerts antiestrogenic activities through a novel progesterone receptor A form-mediated mechanism. J. Biol. Chem.269, 11945–11949 (1994).
   PubMed Web of Science ®Google Scholar
• Zelinski Wooten MB, Slayden OD, Chwalisz K et al. Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316: establishment of a regimen that permits normal menstrual cyclicity. Hum. Reprod.13, 259–267 (1998).
   PubMed Web of Science ®Google Scholar
• Chwalisz K, Brenner RM, Fuhrmann UU, Hess Stumpp H, Elger W. Antiproliferative effects of progesterone antagonists and progesterone receptor modulators on the endometrium. Steroids65, 741–751 (2000).
   PubMed Web of Science ®Google Scholar
• Koji T, Chedid M, Rubin JS et al. Progesterone-dependent expression of keratinocyte growth factor mRNA in stromal cells of the primate endometrium: keratinocyte growth factor as a progestomedin. J. Cell Biol.125, 393–401 (1994).
   PubMed Web of Science ®Google Scholar
• Grow DR, Reece MT, Hsiu JG et al. Chronic antiprogestin therapy produces a stable atrophic endometrium with decreased fibroblast growth factor: a 1-year primate study on contraception and amenorrhea. Fertil. Steril.69, 936–943 (1998).
   PubMed Web of Science ®Google Scholar
• Greb RR, Heikinheimo O, Williams RF, Hodgen GD, Goodman AL. Vascular endothelial growth factor in primate endometrium is regulated by oestrogen-receptor and progesterone-receptor ligands in vivo. Hum. Reprod.12, 1280–1292 (1997).
   PubMed Web of Science ®Google Scholar
• Heikinheimo O, Hsiu JG, Gordon K et al. Endometrial effects of RU486 in primates – antiproliferative action despite signs of estrogen action and increased cyclin-B expression. J. Steroid Biochem. Mol. Biol.59, 179–190 (1996).
   PubMed Web of Science ®Google Scholar
• Parthasarathy S, Morales AJ, Murphy AA. Antioxidant: a new role for RU-486 and related compounds. J. Clin. Invest.94, 1990–1995 (1994).
   PubMed Web of Science ®Google Scholar
• Englund K, Blanck A, Gustavsson I et al. Sex steroid receptors in human myometrium and fibroids: changes during the menstrual cycle and gonadotropin-releasing hormone treatment. J. Clin. Endocrinol. Metab.83, 4092–4096 (1998).
   PubMed Web of Science ®Google Scholar
• Brandon DD, Bethea CL, Strawn EY et al. Progesterone receptor messenger ribonucleic acid and protein are overexpressed in human uterine leiomyomas. Am. J. Obstet. Gynecol.169, 78–85 (1993).
   PubMed Web of Science ®Google Scholar
• Croxatto HB, Salvatierra AM, Croxatto HD, Fuentealba B. Effects of continuous treatment with low dose mifepristone throughout one menstrual cycle. Hum. Reprod.8, 201–207 (1993).
   PubMed Web of Science ®Google Scholar
• Chwalisz K, Perez MC, Demanno D et al. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr. Rev.26, 423–438 (2005).
   PubMed Web of Science ®Google Scholar
• Narvekar N, Critchley HO, Cheng L, 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, 2312–2318 (2006).
   PubMed Web of Science ®Google Scholar
• Shoupe D, Mishell DR, Jr, Page MA et al. Effects of the antiprogesterone RU 486 in normal women. II. Administration in the late follicular phase. Am. J. Obstet. Gynecol.157, 1421–1426 (1987).
   PubMed Web of Science ®Google Scholar
• Batista MC, Cartledge TP, Zallmer AW et al. Evidence for a critical role of progesterone in the regulation of the midcyle gonadotropin surge and ovulation. J. Clin. Endocrinol. Metab.74, 565–570 (1992).
   PubMed Web of Science ®Google Scholar
• Croxatto HB, Kovacs L, Massai R et al. Effects of long-term low-dose mifepristone on reproductive function in women. Hum. Reprod.13, 793–798 (1998).
   PubMed Web of Science ®Google Scholar
• Cameron ST, Critchley HO, Thong KJ et al. Effects of daily low dose mifepristone on endometrial maturation and proliferation. Hum. Reprod.11, 2518–2526 (1996).
   PubMed Web of Science ®Google Scholar
• Chwalisz K, Elger W, Stickler T, MattiaHGoldberg C, Larsen L. The effects of one-month administration of asoprisnil (J867), a selective progesterone receptor modulator, in normal women. Hum. Reprod.20, 1090–1099 (2005).
   PubMed Web of Science ®Google Scholar
• Grow DR, Williams RF, Hsiu JG, Hodgen GD. Antiprogestin and/or gonadotropin-releasing hormone agonist for endometriosis treatment and bone maintenance: a 1-year primate study. J. Clin. Endocrinol. Metab.81, 1933–1939 (1996).
   PubMed Web of Science ®Google Scholar
• Spitz IM. Progesterone antagonists and progesterone receptor modulators: an overview. Steroids68, 981–993 (2003).
   PubMed Web of Science ®Google Scholar
• Christian R, Stratton P, Merino M et al. The selective progesterone receptor modulator CDB-2914 has estrogenic and anti-estrogenic effects in menopausal women. The Endocrine Society, 84th Annual Meeting. San Francisco, CA, USA 19–22 June 2002 (Abstract 3–38).
   Google Scholar
• Wang C, Sinha Hikim A, Leung A. The anti-progestin CDB 2914 has no antifertility effect in male rats. Contraception51, 215–218 (1995).
   PubMed Web of Science ®Google Scholar
• Steinauer J, Pritts EA, Jackson R, Jacoby AF. Systematic review of mifepristone for the treatment of uterine leiomyomata. Obstet. Gynecol.103, 1331–1336 (2004).
   PubMed Web of Science ®Google Scholar
• Eisinger SH, Bonfiglio T, Fiscella K, Meldrum S, Guzick DS. Twelve-month safety and efficacy of low-dose mifepristone for uterine myomas. J. Minim. Invasive Gynecol.12, 227–233 (2005).
   PubMed Web of Science ®Google Scholar
• Eisinger SH, Meldrum S, Fiscella K, le Roux HD, Guzick DS. Low-dose mifepristone for uterine leiomyomata. Obstet. Gynecol.101, 243–250 (2003).
   PubMed Web of Science ®Google Scholar
• Chwalisz K, Larsen L, McCrary K, Edmonds A. Effects of the novel selective progesterone receptor modulator (SPRM) asoprisnil on bleeding patterns in subjects with leiomyomata. J. Soc. Gynecol. Invest.11(Suppl. 2), 728 (2004).
   Google Scholar
• Kettel LM, Murphy AA, Morales AJ et al. Rapid regression of uterine leiomyomas in response to daily administration of gonadotropin-releasing hormone antagonist. Fertil. Steril.60, 642–646 (1993).
   PubMed Web of Science ®Google Scholar
• Kettel LM, Murphy AA, Morales AJ et al. Treatment of endometriosis with the antiprogesterone mifepristone (RU486). Fertil. Steril.65, 23–28 (1996).
   PubMed Web of Science ®Google Scholar
• Kettel LM, Murphy AA, Morales AJ, Yen SS. Preliminary report on the treatment of endometriosis with low-dose mifepristone (RU 486). Am. J. Obstet. Gynecol.178, 1151–1156 (1998).
   PubMed Web of Science ®Google Scholar
• Chwalisz K, Mattia-Goldberg K, Lee M, Elger W, Edmonds A. Treatment of endometriosis with the novel selective progesterone receptor modulator (SPRM) asoprisnil. Fertil. Steril.82, S83 (2004).
   Google Scholar
• Broekmans FJ. GnRH agonists and uterine leiomyomas. Hum. Reprod.11(Suppl. 3), 3–25 (1996).
   PubMed Web of Science ®Google Scholar
• Yen SSC. Use of antiprogestins in the management of endometriosis and leiomyoma. In: Clinical Applications of Mifepristone (RU496) and other Antiprogestins. Donaldson MS, Dorflinger L, Brown SS, Benet LZ (Eds). National Academy Press, DC, USA, 189–209 (1993).
   Google Scholar
• Gemzell Danielsson K, Swahn ML, Westlund P et al. Effect of low daily doses of mifepristone on ovarian function and endometrial development. Hum. Reprod.12, 124–131 (1997).
   PubMed Web of Science ®Google Scholar
• von Hertzen H, van Look PF. Antiprogestins for contraception? Semin. Reprod. Med.23, 92–100 (2005).
   PubMed Web of Science ®Google Scholar
• Spitz IM, van Look PF, Coelingh Bennink HJ. The use of progesterone antagonists and progesterone receptor modulators in contraception. Steroids65, 817–823 (2000).
   PubMed Web of Science ®Google Scholar
• Yang J, Serres C, Philibert D et al. Progesterone and RU486: opposing effects on human sperm. Proc. Natl Acad. Sci. USA91, 529–533 (1994).
   PubMed Web of Science ®Google Scholar
• Uhler ML, Leung A, Chan SY, Wang C. Direct effects of progesterone and antiprogesterone on human sperm hyperactivated motility and acrosome reaction. Fertil. Steril.58, 1191–1198 (1992).
   PubMed Web of Science ®Google Scholar
• Brown A, Cheng L, Lin S, Baird DT. 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, 63–70 (2002).
   PubMed Web of Science ®Google Scholar
• Croxatto HB, Massai MR, Salvatierra AM et al. Effects of a sequential regimen of mifepristone-medroxyprogesterone acetate on ovarian function, endometrial development and hormonal parameters. Contraception54, 79–86 (1996).
   PubMed Web of Science ®Google Scholar
• Croxatto HB, Salvatierra AM, Fuentealba B, Massai R. Contraceptive potential of a mifepristone-nomegestrol acetate sequential regimen in women. Hum. Reprod.13, 3297–3302 (1998).
   PubMed Web of Science ®Google Scholar
• Massai R, Forcelledo ML, Quinteros E, Fuentealba B, Croxatto H. Anticoncepcion oral libre de estrogenos: regimen secuencial antiprogestina-progestina. Cuban J. Pub. Health29, R104 (2003).
   Web of Science ®Google Scholar
• Gemzell Danielsson K, Swahn ML, Svalander P, Bygdeman M. Early luteal phase treatment with mifepristone (RU 486) for fertility regulation. Hum. Reprod.8, 870–873 (1993).
   PubMed Web of Science ®Google Scholar
• Hapangama DK, Brown A, Glasier AF, Baird DT. Feasibility of administering mifepristone as a once a month contraceptive pill. Hum. Reprod.16, 1145–1150 (2001).
   PubMed Web of Science ®Google Scholar
• Gemzell Danielsson K, Svalander P, Swahn ML, Johannisson E, Bygdeman M. Effects of a single post-ovulatory dose of RU486 on endometrial maturation in the implantation phase. Hum. Reprod.9, 2398–2404 (1994).
   PubMed Web of Science ®Google Scholar
• Sarkar NN. The potential of mifepristone (RU486) as a female contraceptive drug. Int. J. Clin. Pract.56, 140–144 (2002).
   PubMed Web of Science ®Google Scholar
• Bygdeman M, Danielsson KG, Marions L, Swahn ML. Contraceptive use of antiprogestin. Eur. J. Contracept. Reprod. Health Care4, 103–107 (1999).
   PubMedGoogle Scholar
• Marions L, Danielsson KG, Swahn ML, Bygdeman M. Contraceptive efficacy of low doses of mifepristone. Fertil. Steril.70, 813–816 (1998).
   PubMed Web of Science ®Google Scholar
• Borman SM, Chwalisz K, Stouffer RL, Zelinski-Wooten MB. Chronic low-dose antiprogestin impairs preimplantation embryogenesis, but not oocyte nuclear maturation or fertilization in rhesus monkeys. Steroids68, 1041–1051 (2003).
   PubMed Web of Science ®Google Scholar
• Marions L, Viski S, Gemzell-Danielsson K et al. Contraceptive efficacy of daily administration of 0.5 mg mifepristone. Hum. Reprod.14, 2788–2790 (1999).
   PubMed Web of Science ®Google Scholar
• Spitz IM, Croxatto HB, Salvatierra AM, Heikinheimo O. Response to intermittent RU486 in women. Fertil. Steril.59, 971–975 (1993).
   PubMed Web of Science ®Google Scholar
• Chen X, Xiao B. Effect of once weekly administration of mifepristone on ovarian function in normal women. Contraception56, 175–180 (1997).
   PubMed Web of Science ®Google Scholar
• Gemzell Danielsson K, Westlund P, Johannisson E et al. Effect of low weekly doses of mifepristone on ovarian function and endometrial development. Hum. Reprod.11, 256–264 (1996).
   PubMed Web of Science ®Google Scholar
• Godfrey EM, Mawson JT, Stanwood NL, Fielding SL, Schaff EA. Low-dose mifepristone for contraception: a weekly versus planned postcoital randomized pilot study. Contraception70, 41–46 (2004).
   PubMed Web of Science ®Google Scholar
• Cheng J, Weng L, Han X. Study on weekly low doses of mifepristone for contraception. Zhonghua Fu Chan Ke Za Zhi36, 424–427 (2001).
   PubMedGoogle Scholar
• Swahn ML, Bygdeman M, Chen JK et al. Once-a-month treatment with a combination of mifepristone and the prostaglandin analogue misoprostol. Hum. Reprod.14, 485–458 (1999).
   PubMed Web of Science ®Google Scholar
• Spitz IM, Croxatto HB, Robbins A. Antiprogestins: mechanism of action and contraceptive potential. Ann. Rev. Pharmacol. Toxicol.36, 47–81 (1996).
   PubMed Web of Science ®Google Scholar
• Cheng L, Zhu H, Wang A et al. Once a month administration of mifepristone improves bleeding patterns in women using subdermal contraceptive implants releasing levonorgestrel. Hum. Reprod.15, 1969–1972 (2000).
   PubMed Web of Science ®Google Scholar
• Massai MR, Pavez M, Fuentealba B, Croxatto HB, d’Arcangues C. Effect of intermittent treatment with mifepristone on bleeding patterns in Norplant implant users. Contraception70, 47–54 (2004).
   PubMed Web of Science ®Google Scholar
• Jain JK, Nicosia AF, Nucatola DL et al. Mifepristone for the prevention of breakthrough bleeding in new starters of depo-medroxyprogesterone acetate. Steroids68, 1115–1119 (2003).
   PubMed Web of Science ®Google Scholar
• Weisberg E, Hickey M, Palmer D et al. 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, 295–302 (2006).
   PubMed Web of Science ®Google Scholar
• Verbost PM, Hanssen RGJM, Korver GHV, Mulders TMT. ORG 33628 and ORG 31710 control vaginal bleeding in progestin-only contraceptive regimens. Semin. Reprod. Med.23, 101–11 (2005).
   PubMed Web of Science ®Google Scholar
• van Heusden AM, Killick SR, Coelingh Bennink HJ, Fauser BC. Single monthly administration of the anti-progestagen ORG 31710 in users of the 75 microg desogestrel progestagen-only pill: effects on pituitary-ovarian activity. Hum. Reprod.15, 629–636 (2000).
   PubMed Web of Science ®Google Scholar
• Gemzell Danielsson K, van Heusden AM, Killick SR et al. Improving cycle control in progestogen-only contraceptive pill users by intermittent treatment with a new anti-progestogen. Hum. Reprod.17, 2588–2593 (2002).
   PubMed Web of Science ®Google Scholar
• Glasier A, Thong KJ, Dewar M, Mackie M, Baird DT. Mifepristone (RU 486) compared with high-dose estrogen and progestogen for emergency postcoital contraception. N. Engl. J. Med.327, 1041–1044 (1992).
   PubMed Web of Science ®Google Scholar
• Webb AM, Russell J, Elstein M. Comparison of Yuzpe regimen, danazol, and mifepristone (RU486) in oral postcoital contraception. Br. Med J.305, 927–931 (1992).
   PubMed Web of Science ®Google Scholar
• Ashok PW, Stalder C, Wagaarachchi PT et al. A randomised study comparing a low dose of mifepristone and the Yuzpe regimen for emergency contraception. Br. J. Obstet Gynaecol.109, 553–560 (2002).
   Google Scholar
• von Hertzen H, Piaggio G, Ding J et al. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial. Lancet360, 1803–1810 (2002).
   PubMed Web of Science ®Google Scholar
• Ashok PW, Wagaarachchi PT, Flett GM, Templeton A. Mifepristone as a late post-coital contraceptive. Hum. Reprod.16, 72–75 (2001).
   PubMed Web of Science ®Google Scholar
• World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation. Comparison of three single doses of mifepristone as emergency contraception: a randomised trial. Lancet353, 697–702 (1999).
   PubMed Web of Science ®Google Scholar
• Xiao BL, von Hertzen H, Zhao H, Piaggio G. A randomized double-blind comparison of two single doses of mifepristone for emergency contraception. Hum. Reprod.17, 3084–3089 (2002).
   PubMed Web of Science ®Google Scholar
• Trussell J, Rodriguez G, Ellertson C. New estimates of the effectiveness of the Yuzpe regimen of emergency contraception. Contraception57, 363–369 (1998).
   PubMed Web of Science ®Google Scholar
• Wilcox AJ, Weinberg CR, Baird DD. Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby. N. Engl. J. Med.333, 1517–1521 (1995).
   PubMed Web of Science ®Google Scholar
• Piaggio G, von Hertzen H, Heng Z, Bilian X, Cheng L. Meta-analyses of randomized trials comparing different doses of mifepristone in emergency contraception. Contraception68, 447–452 (2003).
   PubMed Web of Science ®Google Scholar
• Sitruk-Ware R, Davey A, Sakiz E. Fetal malformation and failed medical termination of pregnancy. Lancet352, 323 (1998).
   PubMed Web of Science ®Google Scholar
• Gonzalez CH, Marques Dias MJ, Kim CA et al. Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy. Lancet351, 1624–1627 (1998).
   PubMed Web of Science ®Google Scholar
• Gonzalez CH, Vargas FR, Perez AB et al. 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.47, 59–64 (1993).
   PubMed Web of Science ®Google Scholar
• Fonseca W, Alencar AJ, Mota FS, Coelho HL. Misoprostol and congenital malformations. Lancet338, 56 (1991).
   PubMed Web of Science ®Google Scholar
• Pastuszak AL, Schuler L, Speck Martins CE et al. Use of misoprostol during pregnancy and Mobius’ syndrome in infants. N. Engl. J. Med.338, 1881–1885 (1998).
   PubMed Web of Science ®Google Scholar
• de Keizer RJ, Smit JW. Mifepristone treatment in patients with surgically incurable sphenoid-ridge meningioma: a long-term follow-up. Eye18, 954–958 (2004).
   PubMed Web of Science ®Google Scholar
• Heikinheimo O, Ranta S, Grunberg S, Lahteenmaki P, Spitz IM. Alterations in the pituitary-thyroid and pituitary–adrenal axes – consequences of long-term mifepristone treatment. Metabolism46, 292–296 (1997).
   PubMed Web of Science ®Google Scholar
• Grunberg SM, Rankin C, Townsend J et al. Phase III double-blind randomized placebo-controlled study of mifepristone (RU) for the treatment of unresectable meningioma. American Society of Clinical Oncology. San Francisco, CA, USA, 26–28 January 2001.
   Google Scholar
• Martineau PA, Levental M. Large endometrial polyp in a patient on long-term mifepristone therapy. J. Ultrasound Med.19, 487–489 (2000).
   PubMed Web of Science ®Google Scholar
• Newfield RS, Spitz IM, Isacson C, New MI. Long-term mifepristone (RU486) therapy resulting in massive benign endometrial hyperplasia. Clin. Endocrinol. (Oxf)54, 399–404 (2001).
   PubMed Web of Science ®Google Scholar
• Fleischer AC, Wheeler JE, Yeh IT et al. Sonographic assessment of the endometrium in osteopenic postmenopausal women treated with idoxifene. J. Ultrasound Med.18, 503–512 (1999).
   PubMed Web of Science ®Google Scholar
• Liedman R, Lindahl B, Andolf E et al. Disaccordance between estimation of endometrial thickness as measured by transvaginal ultrasound compared with hysteroscopy and directed biopsy in breast cancer patients treated with tamoxifen. Anticancer Res.20, 4889–4891 (2000).
   PubMed Web of Science ®Google Scholar
• Murphy AA, Castellano PZ. RU486: pharmacology and potential use in the treatment of endometriosis and leiomyomata uteri. Curr. Opin. Obstet. Gynecol.6, 269–278 (1994).
   PubMed Web of Science ®Google Scholar
• Progesterone Receptor Modulators and the Endometrium – Changes and Consequences. NIH meeting. Washington, DC, USA, 7–8 April 2006.
   Google Scholar
• Slayden OD, Zelinski MB, Chwalisz K, Hess-Stumpp H, Brenner RM. Chronic progesterone antagonist–estradiol therapy suppresses breakthrough bleeding and endometrial proliferation in a menopausal macaque model. Hum. Reprod.21(12), 3081–3090 (2006).
   PubMed Web of Science ®Google Scholar
• Klijn JG, Setyono Han B, Foekens JA. Progesterone antagonists and progesterone receptor modulators in the treatment of breast cancer. Steroids65, 825–830 (2000).
   PubMed Web of Science ®Google Scholar
• Rocereto TF, Saul HM, Aikins JA Jr, Paulson J. Phase II study of mifepristone (RU486) in refractory ovarian cancer. Gynecol. Oncol.77, 429–432 (2000).
   PubMed Web of Science ®Google Scholar
• Mote PA, Balleine RL, McGowan EM, Clarke CL. Heterogeneity of progesterone receptors A and B expression in human endometrial glands and stroma. Hum. Reprod.15(Suppl. 3), 48–56 (2000).
   PubMed Web of Science ®Google Scholar
• Arnett-Mansfield RL, DeFazio A, Mote PA, Clarke CL. Subnuclear distribution of progesterone receptors A and B in normal and malignant endometrium. J. Clin. Endocrinol. Metab.89, 1429–1442 (2004).
   PubMed Web of Science ®Google Scholar
• McGowan EM, Saad S, Bendall LJ, Bradstock KF, Clarke CL. Effect of progesterone receptor a predominance on breast cancer cell migration into bone marrow fibroblasts. Breast Cancer Res. Treat.83, 211–220 (2004).
   PubMed Web of Science ®Google Scholar
• Berrodin TJ, Jelinsky SA, Graciani N, Winneker RC, Yudt MR. Selective activation of PR-a regulated genes by piperazine carboximidothioic acid esters in T47D mammary gland ductal carcinoma cells. Endocrine Society meeting. Boston, MA, USA, 2–27 June 2006 (Abstract 1–520).
   Google Scholar
• Fuhrmann U. ZK-PR-A: a uterus-selective nonsteroidal PR modulator. 12th International Congress on Hormonal Steroids and Hormones and Cancer. Athens, Greece, 2–16 September 2006 (Abstract 89).
   Google Scholar
• Wang XJ, Liefer KM, Tsai S, O’Malley BW, Roop DR. Development of gene-switch transgenic mice that inducibly express transforming growth factor β1 in the epidermis. Proc. Natl Acad. Sci. USA96, 8483–8488 (1999).
   PubMed Web of Science ®Google Scholar
• Burcin MM, Schiedner G, Kochanek S, Tsai SY, O’Malley BW. Adenovirus-mediated regulable target gene expression in vivo. Proc. Natl Acad. Sci. USA96, 355–360 (1999).
   PubMed Web of Science ®Google Scholar
• Smith LC, Nordstrom JL. Advances in plasmid gene delivery and expression in skeletal muscle. Curr. Opin. Mol. Ther.2, 150–154 (2000).
   PubMed Web of Science ®Google Scholar