LEADER 10741nam 2200673 a 450 001 9910817002103321 005 20240416234907.0 010 $a1-280-19602-5 010 $a9786610196029 010 $a0-309-59835-4 010 $a0-585-02478-2 035 $a(CKB)110986584751352 035 $a(SSID)ssj0000123477 035 $a(PQKBManifestationID)11143357 035 $a(PQKBTitleCode)TC0000123477 035 $a(PQKBWorkID)10005859 035 $a(PQKB)10618493 035 $a(MiAaPQ)EBC3376668 035 $a(Au-PeEL)EBL3376668 035 $a(CaPaEBR)ebr10056944 035 $a(OCoLC)923265433 035 $a(EXLCZ)99110986584751352 100 $a19931027d1993 uy 0 101 0 $aeng 135 $aurcn||||||||| 181 $ctxt 182 $cc 183 $acr 200 00$aClinical applications of mifepristone (RU 486) and other antiprogestins $eassessing the science and recommending a research agenda /$fCommittee on Antiprogestins: Assessing the Science, Division of Health Promotion and Disease Prevention, Institute of Medicine ; Molla S. Donaldson ... [et al.], editors 205 $a1st ed. 210 $aWashington, D.C. $cNational Academy Press$d1993 215 $axi, 288 p. $cill 300 $a"Support for this project was provided by a grant from the Henry J. Kaiser Family Foundation, Menlo Park, California."--Verso T.p. 300 $aCommittee chairman: Leslie Z. Benet. 311 $a0-309-04949-0 320 $aIncludes bibliographical references and index. 327 $aClinical Applications of Mifepristone (RU 486) and Other Antiprogestins -- Copyright -- Preface -- Contents -- Summary -- CROSS-CUTTING RECOMMENDATIONS -- USES OF ANTIPROGESTINS: THE REPRODUCTIVE CYCLE -- Contraception -- Post-Coital Contraception -- Menses Induction -- Pregnancy Termination During the First Trimester -- Pregnancy Termination During the Second Trimester -- Cervical Ripening -- Labor Induction in Late Pregnancy -- OTHER POTENTIAL THERAPEUTIC USES OF ANTIPROGESTINS -- Endometriosis -- Uterine Leiomyomas (Fibroids) -- Breast Cancer -- Meningioma -- ANTIGLUCOCORTICOID EFFECTS OF ANTIPROGESTINS -- 1 Introduction -- BACKGROUND AND HISTORICAL PERSPECTIVES -- Finding an Antiprogestin -- THE IOM REPORT -- CROSS-CUTTING RECOMMENDATIONS -- REFERENCES -- 2 Uses of Antiprogestins: The Reproductive Cycle (Part I) -- CONTRACEPTION -- POST-COITAL CONTRACEPTION -- MENSES INDUCTION -- REFERENCES -- 3 Uses of Antiprogestins: The Reproductive Cycle (Part II) -- PREGNANCY TERMINATION DURING THE FIRST TRIMESTER -- Health Services Research -- PREGNANCY TERMINATION DURING THE SECOND TRIMESTER -- CERVICAL RIPENING -- LABOR INDUCTION IN LATE PREGNANCY -- Fetal Demise -- SUMMARY -- REFERENCES -- 4 Other Therapeutic Uses of Antiprogestins -- ENDOMETRIOSIS -- Utility of Mifepristone (RU 486) for Treatment of Endometriosis -- Summary -- UTERINE LEIOMYOMAS (FIBROIDS) -- Utility of Mifepristone for Treatment of Uterine Leiomyomas -- BREAST CANCER -- Mechanism of Action -- Clinical Issues -- Adjuvant Therapy and Chemoprevention -- Resistance -- Dose Issues -- Conclusions -- MENINGIOMAS -- Conclusions -- REFERENCES -- 5 Antiglucocorticoid Effects of Antiprogestins -- GLUCOCORTICOID FUNCTION -- THERAPEUTIC USE OF MIFEPRISTONE (RU 486) AS ANANTIGLUCOCORTICOID -- ADVERSE ANTIGLUCOCORTICOID EFFECTS OF ANTIPROGESTINS -- REFERENCES. 327 $a6 Animals as Models for Studying Antiprogestins -- REFERENCES -- APPENDIXES -- A Agenda for the IOM Workshop ''Antiprogestins: Assessing the Science," April 13-14, 1993 -- B Background Papers and Presentations (In Order of Presentation at IOM Workshop) -- B1 1993: RU 486-A DECADE ON TODAY AND TOMORROW -- ANTIHORMONES: THE 20 YEARS BEFORE RU 486 -- CHEMISTRY: NOVEL MOLECULES -- CELLULAR AND MOLECULAR MECHANISMS OF ACTION OF ANTIPROGESTINS: THE RECEPTOR AT THE CENTER -- Ligand Binding -- Receptor Transconformation -- Heat Shock Protein Binding -- Receptor Dimerization -- Binding to DNA -- Studies of Chromatin -- Gene Transcription -- PHYSIOPHARMACOLOGICAL REPRODUCTIVE EFFECTS -- REPRODUCTIVE MEDICINE (TABLE B1.4) -- Voluntary Early Pregnancy Interruption -- Pregnancy Interruption After Nine Weeks of Amenorrhea -- Initiation of Labor -- Contragestive and Contraceptive Methods Using RU 486 -- Emergency Post-Coital Contraception (Contraceptive or Contragestive According to When it is Applied) -- Late Luteal Phase Administration (Occasional Use) (Contragestive) -- Monthly Premenstrual, Late Luteal Phase Administration (Repeated Use) (Contragestive) -- Early Luteal Phase Administration (Once a Month) (Anti-Implantation) -- Endometrial Contraception" (Daily Delivery of Very Low Dose) (Contraceptive and Contragestive) -- Ovulation Suppression (Daily Delivery of a Low Dose) (Contraceptive) -- Male Contraception -- MEDICAL APPLICATIONS (TABLE B1.4) -- Uterine Diseases -- Endometriosis -- Fibroids -- Breast Cancer -- Meningioma -- ANTIGLUCOCORTICOSTEROID EFFECTS -- CONCLUSIONS -- Use for Voluntary Pregnancy Interruption -- Contraception -- Cancer -- Novel Antiprogestins: Biology and Chemistry -- ACKNOWLEDGMENTS -- REFERENCES -- B2 OVERVIEW AND BACKGROUND: MECHANISM OF ACTION OF ANTIPROGESTINS -- INTRODUCTION -- STRUCTURE AND FUNCTION OF THE PROGESTERONE RECEPTOR. 327 $aThe Hormone Binding Domain -- The DNA Binding Domain -- Transactivation Function -- Association with Other Proteins -- Phosphorylation of the Progesterone Receptor -- Progesterone-Receptor Function -- MECHANISMS OF ACTION OF PROGESTERONE ANTAGONISTS -- Binding of Antagonists to Progesterone Receptors -- Formation of Dimers and DNA Binding Complexes -- Effects of Antagonists on Transcriptional Activation -- Other Effects of Antagonists on Receptors -- SUMMARY AND FUTURE AREAS OF STUDY -- REFERENCES -- B3 THE USE OF ANTIPROGESTINS IN THE REPRODUCTIVE CYCLE -- USE OF ANTIPROGESTINS IN THE REPRODUCTIVE CYCLE -- Basic Concepts and Assumptions -- Assessment Issues in Evaluating Antiprogestins -- Potential Uses of Antiprogestins -- Follicular Phase Administration of RU 486 -- Other Strategies for Administration of RU 486 During the Menstrual Cycle -- TOXICITY -- QUESTIONS FOR FUTURE RESEARCH -- SUMMARY -- REFERENCES -- B4 POTENTIAL CONTRACEPTIVE EFFECTS OF ANTIGESTOGENS -- ABSTRACT -- INTRODUCTION -- PHYSIOLOGICAL STUDIES IN THE MENSTRUAL CYCLE -- POSSIBLE CONTRACEPTIVE USES OF MIFEPRISTONE -- Inhibition of Ovulation -- Post-Coital Contraception -- Endometrial Contraception -- Late Post-Coital Contraception -- FUTURE DEVELOPMENTS -- Basic Research -- Mode of Action -- Clinical Studies -- REFERENCES -- B5 USE OF ANTIPROGESTINS BEFORE 63 DAYS OF AMENORRHEA -- INTRODUCTION -- EFFECT OF MIFEPRISTONE DURING EARLY PREGNANCY -- TERMINATION OF EARLY PREGNANCY -- Mifepristone Alone -- Mifepristone in Combination with Prostaglandin -- Practical Guidelines for Clinical Use of Mifepristone in Combination with Prostaglandin -- FURTHER DEVELOPMENTS IN MEDICAL TERMINATION OF EARLY PREGNANCY -- CONCLUSIONS -- REFERENCES -- B6 USES OF ANTIPROGESTINS AFTER 63 DAYS OF AMENORRHEA -- RU 486 FOR SECOND-TERM PREGNANCY TERMINATION -- RU 486 FOR INTRAUTERINE FETAL DEATH (IUFD). 327 $aCERVICAL RIPENING WITH RU 486 PRIOR TO SURGICAL ABORTION -- RU 486 FOR LABOR INDUCTION -- REFERENCES -- B7 COMMENTS ON SESSION II -- USE OF MIFEPRISTONE AND PROSTAGLANDIN FOR FIRST-TRIMESTER ABORTION -- Need for Medical Supervision -- Acceptability of Medical Versus Surgical Abortion -- Number of Visits Required -- Appropriate Dose of Mifepristone -- Side Effects -- SECOND-TRIMESTER ABORTIONS -- CONTRACEPTION -- POST-COITAL CONTRACEPTION -- CERVICAL RIPENING -- SUMMARY -- B8 USE OF ANTIPROGESTINS IN THE MANAGEMENT OF ENDOMETRIOSIS AND LEIOMYOMA -- ABSTRACT -- INTRODUCTION -- ENDOMETRIOSIS -- Antiprogestin in the Treatment of Endometriosis -- Pilot Study -- Long-Term, Low-Dose Studies -- LEIOMYOMA (FIBROID TUMOR) -- Antiprogestin in the Management of Leiomyoma- Dose-Response Studies -- 50-mg Dose -- 25- and 5-mg Doses -- Outcome -- ACKNOWLEDGMENTS -- REFERENCES -- B9 ANTIPROGESTINS AND THE TREATMENT OF BREAST CANCER -- INTRODUCTION -- PROGESTERONE AND THE NORMAL BREAST -- PROGESTERONE AND BREAST CANCER -- Progestin Agonists and Tumor Induction -- Progestin Agonists and Growth of Established Tumors -- PROGESTERONE ANTAGONISTS AND THE TREATMENT OF BREAST CANCER -- Human Breast Cancer Cell Lines -- Animal Models of Mammary Cancer -- Human Clinical Trials -- PROGESTIN RESISTANCE -- SUMMARY AND FUTURE PROSPECTS -- REFERENCES -- B10 USES OF RU 486 AS AN ANTIGLUCOCORTICOID -- HOW DO GLUCOCORTICOIDS ACT? -- PHYSIOLOGIC ROLE OF GLUCOCORTICOIDS -- RU 486 AS AN ANTIGLUCOCORTICOID -- RESEARCH DIRECTIONS FOR ANTIGLUCOCORTICOIDS -- REFERENCES -- B11 PRIMATE MODELS FOR THE STUDY OF ANTIPROGESTINS IN REPRODUCTIVE MEDICINE -- PART I: ACTIVITY EXPRESSIONS OF ANTIPROGESTINS -- Progesterone Antagonists -- Antiglucocorticoid Activity -- Noncompetitive Antiestrogenic (Antiproliferative) Activity -- Sources of Antiprogestins. 327 $aPART II: NONCOMPETITIVE ANTIESTROGENIC ACTIVITY OF PROGESTERONE ANTAGONISTS -- Initial Evidence of Noncompetitive Antiestrogenic Activity of Mifepristone -- Dose-Dependent Blockade of the Proliferative Action of Estradiol Endometrium by Mifepristone -- Mifepristone-Induced Elevations of Estrogen Receptor in Primate Endometrium -- REFERENCES -- B12 ANTIPROGESTOGENS: PERSPECTIVES FROM A GLOBAL RESEARCH PROGRAM -- ABSTRACT -- INTRODUCTION -- COMPOUNDS -- Progesterone Synthesis Inhibitors -- Progesterone-Receptor Blockers -- ANIMAL MODELS -- Receptor Binding -- Plasma Protein Binding -- Pregnant Guinea Pig Model -- MECHANISMS OF ACTION -- Prostaglandin Metabolism -- Myometrial Gap Junctions -- Estrogen and Progesterone Receptors -- POSSIBLE USES -- PROSPECTS -- ACKNOWLEDGMENT -- REFERENCES -- C Observers at the Workshop on Antiprogestins: Assessing the Science April 13-14, 1993 -- Index. 606 $aMifepristone$xResearch 606 $aAbortifacients$xResearch 606 $aProgesterone$xAntagonists$xResearch 615 0$aMifepristone$xResearch. 615 0$aAbortifacients$xResearch. 615 0$aProgesterone$xAntagonists$xResearch. 676 $a615/.766 701 $aBenet$b Leslie Z$096362 701 $aDonaldson$b Molla S$01604881 712 02$aInstitute of Medicine (U.S.).$bCommittee on Antiprogestins: Assessing the Science. 712 02$aInstitute of Medicine (U.S.).$bDivision of Health Promotion and Disease Prevention. 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910817002103321 996 $aClinical applications of mifepristone (RU 486) and other antiprogestins$93973876 997 $aUNINA