Clinical applications of mifepristone (RU 486) and other antiprogestins : assessing the science and recommending a research agenda

Clinical applications of mifepristone (RU 486) and other antiprogestins assessing the science and recommending a research agenda

Detalles Bibliográficos
Autores Corporativos: Institute of Medicine (U.S.). Committee on Antiprogestins: Assessing the Science (-), Institute of Medicine (U.S.). Division of Health Promotion and Disease Prevention
Otros Autores: Benet, Leslie Z. (-), Donaldson, Molla S.
Formato: Libro electrónico
Idioma:Inglés
Publicado: Washington, D.C. : National Academy Press 1993.
Edición:1st ed
Materias:
Mifepristone > Research.
Abortifacients > Research.
Progesterone > Antagonists > Research.
Ver en Biblioteca Universitat Ramon Llull:https://discovery.url.edu/permalink/34CSUC_URL/1im36ta/alma991009820335006719
Tabla de Contenidos:
  • Clinical 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.
  • 6 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.
  • The 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).
  • CERVICAL 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.
  • PART 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.

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