5: Pharmacology of Estrogens and Antiestrogens.- In Vitro and In Vivo Models to Characterise Estrogens and Antiestrogens.- A. General Aspects.- I. Physiological Targets of Estrogens.- II. ER Ligands.- III. The Receptors - Mediators of Hormone Action, Targets for Antihormones and Modulators of Gene Expression.- B. In Vitro Methods to Characterise Estrogens and Antiestrogens.- I. Receptor-Binding Assay.- 1. Principle.- 2. Binding of Estrogens and Antiestrogens to Insect- Cell-Produced Human ERa (hERa).- a) Preparation of ER-Containing Cytosol..- b) Competition Experiment.- c) Results.- II. Ligand Effects on DNA Binding of the ER.- III. Transactivation Assays for Detection of Estrogenic and Antiestrogenic Activity.- 1. Principle.- 2. Transactivation Assay with the Vitellogenin A2-ERE-tk-CAT Reporter Gene in HeLa Cells.- a) Comparative Study of the Agonistic Potency of Four Selected Estrogens.- b) Comparative Study of the Antagonistic Potency of Selected Antiestrogens.- 3. Transactivation Assay with MVLN Cell.- 4. Comparative Study of the Transactivational Activity of ERa and ERf3.- 5. Transactivation Assay with an rPR-ERE-tk-CAT Reporter Gene.- IV. Transactivation Assay in Yeast as a Model System to Characterise Estrogenic Compounds.- 1. Principle.- Determination of the Agonistic Activity of Selected Phyto- and Mycoestrogens by Transactivation Assay in Yeast..- The Yeast Strain.- Vector Plasmids.- Recombinant Yeast Strains.- Transactivation Assay.- V. Reporter Assays Based on “Non-Classical” Mechanisms of Gene Activation by the ER.- 1. ER Activation of Genes Through AP-1.- 2. TGF-fJ3 Induction Through a Non-Classical ERE.- a) Study of Raloxifen and ZM182,780 in the TGF-f?Ass.- 3. Repression of the IL-6 Gene Expression by the ER.- VI. Estrogen Effects on Expression of Endogenous Genes in Diverse Cell Lines.- 1. Alkaline Phosphatase and PR Measurement in Ishikawa Endometrial Carcinoma Cells.- 2. The Endometrial Adenocarcinoma Cell Line RUCA-I as an In Vitro/In VivoTumor Model.- 3. Cathepsin D, PS2 and PR Induction in Mammary Cell Lines by Estrogens.- a) Estrogen Effects on the PR Level in MCF-7 Cell.- b) Estrogen Effects on the Cathepsin D and pS2 mRNA Levels and on the PR Protein Level in MCF-7 Cells.- 4. Estrogen Regulation of Prolactin Expression in Pituitary Cell.- 5. Estrogen-Regulated Genes in Liver Hepatoma Cells.- 6. Induction of ERs and Vitellogenin Synthesis in Fish Liver Cells.- VII. Ligand-Induced ER Stabilisation or Destabilisation.- 1. Comparative Study of the Effects of Different Antiestrogens on the ER Level in T47-D Cells.- VIII. Effects of ER Ligands on the Proliferation of ER-Expressing Breast Cancer and Endometrial Cell Lines.- 1. Inhibition of Estrogen-Stimulated Growth of MCF-7 Mammary Carcinoma Cells by Antiestrogens.- Experimental Design.- IX. Antioxidative Activity.- 1. Protection from Amyloid-Induced Neurotoxicity and Prevention of Glutamate-Induced Cell Death in Nerve Cell.- 2. Attenuation of Lipid Peroxidation in Synaptosomal Membranes.- 3. Fe(II) Autoxidation and Fe(III) Reduction Assays.- 4. Oxidation of Low-Density Lipoprotein Cholesterol.- C. In Vivo Test Systems to Characterise Estrogens and Antiestrogens.- I. Allen-Doisy Assay.- 1. Principle.- 2. Study Design.- 3. Scoring Criteria.- 4. Evaluation and Discussion.- II. Vaginal Mitosis and Epithelial Thickness.- 1. Principle.- 2. Study Design.- 3. Evaluation and Discussion.- III. Vaginal Tetrazolium Reduction.- 1. Principle.- 2. Study Design.- 3. Evaluation and Discussion.- IV. Vaginal Opening.- 1. Principle.- 2. Study Design.- 3. Evaluation and Discussion.- V. Vaginotrophic Response.- 1. Principle.- 2. Study Design.- 3. Evaluation and Discussion.- VI. Measurement of Sialic Acid.- 1. Principle.- 2. Study Design.- 3. Evaluation and Discussion.- VII. Uterine Fluid Inhibition (Astwood Bioassay.- 1. Principle.- 2. Study Design.- 3. Evaluation and Discussion.- VIII. Uterine Growth Tes.- 1. Principle.- 2. Study Design.- 3. Evaluation and Discussion.- IX. Regulation of Steroid Hormone Receptors, Proliferation, Differentiation and Protein Expression in the Rodent Uterus.- 1. Principle.- Steroid Hormone Receptors.- Proliferation.- Protooncogenes.- Luminal Epithelial Cell Height.- Uterine Glycogen Deposition.- Peroxidase Activity.- Complement Component C3.- 2. Study Design.- Steroid Hormone Receptors.- Proliferation.- Protooncogenes.- Luminal Epithelial Cell Height.- Uterine Glycogen Deposition.- Peroxidase Activity.- Complement Component C3.- 3. Evaluation and Discussion.- Steroid Hormone Receptors.- Proliferation.- Protooncogenes.- Luminal Epithelial Cell Height.- Uterine Glycogen Deposition.- Peroxidase Activity.- Complement Component C3.- X. Withdrawal Bleeding (Primates).- 1. Principle.- 2. Study Design.- 3. Evaluation and Discussion.- XI. Imaging of the Primate Uterus.- 1. Principle.- 2. Experimental Design.- MRI Evaluation.- Ultrasound Evaluation.- 3. Evaluation and Discussion.- XII. Pituitary Blockade.- Gonadal Growth Methods.- Gonadotropin Methods.- Ovulatory Methods.- D. Transgenic Animals.- I. ERKO Mouse.- Uterus.- Ovary.- Testis.- Mammary Gland.- Behaviour.- II.PR Mutant Mouse.- Uterus.- Ovary.- Mammary Gland.- Behaviour.- References.- Estrogen Receptor ? in the Pharmacology of Estrogens and Antiestrogens.- A. Introduction.- B. Basic Similarities Between ER? and ER?.- C. ER? Isoforms.- D. Role of Ligands in the Tissue-Specific Action of ER?.- E. Tissue Distribution of ER? mRNA and Protein.- F. Multiple Mechanisms of Transcriptional Activation and Repression by ERs.- G. What is the Phenotype of ER? Knockout Mice.- References.- Interrelationship of Estrogens with other Hormones or Endocrine Systems.- A. Introduction.- B. Thyroid Hormone Effects on Estrogen Levels.- C. Estrogen Effects on Thyroid Function.- D. Estrogen Effects on the Gastrointestinal System.- E. Estrogen Effects on the Pancreas.- F. Estrogen Effects on the Parathyroid.- G. Conclusion.- Reference.- Mammary Gland.- A. Pharmacological and Physiological Effects of Estrogens in the Mammary Gland.- I. Introduction.- II. Hormone Action on the Development of the Mammary Gland.- 1. Pregnancy.- III. Proliferation.- 1. Progestogen Effects are Complex.- IV. Apoptosis.- V. Estrogen Action During the Normal Menstrual Cycle.- 1. Estrogen and Progesterone Receptors.- 2. Proliferation.- B. Pharmacological Effects of Exogenous Estrogens and Progestogens in the Mammary Gland.- I. Effects on Proliferation and Sex-Steroid Receptors.- II. Effects on Enzymatic Conversion of Estrogens in Mammary Tissue.- References.- Cardiovascular System.- A. Introduction.- B. Female Cardiovascular Morbidity.- C. Anti-Atherosclerotic Effects.- D. Lipid Metabolism.- E. Haemostatic System.- F. Carbohydrate Metabolism.- G. Blood Pressure.- H. Direct Effects on the Arterial Wall.- I. Antioxidative Effect.- J. Antiestrogens.- References.- Bone.- Bone.- I. Macroscopic Anatom.- II. Microscopic Anatomy.- 1. Matrix and Minerals.- 2. Bone Cells.- 3. Bone Remodeling.- III. Estrogen and Bone.- Reference.- Central Nervous System.- A. Introduction.- B. Estrogens and CNS.- I. Estrogens, Neurotransmitters and Neuropeptides.- II. Estrogen Effects on Neuronal Plasticity.- III. Estrogens and Cognitive Functions.- C. Selective Estrogen Receptor Modulators (SERMs).- I. Introduction.- II. SERMs and CNS.- D. Conclusions.- References.- Liver Inclusive Protein, Lipid and Carbohydrate Metabolism.- A Liver - A Non-Reproductive Target Organ for Estrogens.- I. Regulation of the Hepatic Estrogen Receptor.- II. Exogenous Estrogen.- B. Plasma Proteins.- I. Coagulation Factors.- C. Lipids.- D. Carbohydrates.- References.- Pharmacology of Antiestrogens.- A. Introduction.- B. Reproductive Tract.- C. Breast and Breast Cancer.- D. Bone.- E. Brain.- F. Cardiovascular System.- G. Conclusion.- References.- Oncology.- A. Introduction.- B. Estrogens and Cancer Etiolog.- I. General Considerations.- II. Breast Cancer.- III. Uterine and Cervical Cance.- IV. Ovarian Cancer.- V. Vaginal Adenocarcinoma.- VI. Liver Cancer.- C. Hormones and Cancer Therapy.- I. Hormone-Dependent Neoplasms.- II. Breast Cancer.- 1. Endocrine Ablation.- 2. Antiestrogens.- 3. Aromatase Inhibitors.- 4. Estrogen Receptors.- III.Uterine and Cervical Cancer.- D. Summary.- References.- Hormonal Resistance in Breast Cancer.- A. Introduction.- B. The Estrogen Receptor.- I. The ER’s Ligands.- II. ER Structure: Mutants, Variants and Post-Translational Changes.- III. Transcriptional Activity: Co-Activators and Co-Repressor.- IV. EREs and Promoter Elements.- V. Non-estrogen Response Element-Dependent Pathways.- C. Secondary Resistance.- I. Tumour Adaptation to Estrogen Levels.- II. Tamoxifen Stimulation and Withdrawal Responses.- D. Clinical Implications and New Endocrine Agents.- E. Conclusions.- References.- Pharmacology of Inhibitors of Estrogen Biosynthesis.- A. Introduction.- B. Non-Steroidal and Steroidal Aromatase Inhibitors.- C. Inhibition of Intracellular Aromatase.- References.- Pharmacology of Inhibition of Estrogen-Metabolizing Enzymes.- A. Rationale for Development of Steroid Sulphatase and Estradiol 17,?-Hydroxysteroid Dehydrogenase Inhibitors.- B. Steroid Sulphatase Inhibitors.- I. Substrate Analogue Inhibitors.- II. Identification of the Active Pharmacophore Required for Potent Steroid Sulphatase Inhibition.- III. Development of Potent Non-steroidal, Non-estrogenic Steroid Sulphatase Inhibitors.- IV. Pharmacological Effectiveness of Steroid Sulphatase Inhibition.- C. Estradiol 17,?-Hydroxysteroid Dehydrogenase Inhibitor.- I. Substrate Analogue Inhibitors.- II. Irreversible Inhibitors.- III. Fused A- or D-Ring Pyrazole and Isoxazole Inhibitors.- IV. Inhibitors with Antiestrogenic Properties.- V. Flavone and Isoflavone Inhibitors.- D. Future Perspectives.- References.- Pharmacology of Different Administration Routes - Oral vs Transdermal.- A Rationale for Various Routes of Estrogen Delivery.- B. Estrogens Available for Therapy.- I. Artificial Estrogens.- 1. Ethinyl Estradiol.- 2. Mestranol.- 3. Others.- II. Natural Estrogens.- 1. Conjugated Equine Estrogens (CEE).- 2. Estradiol.- 3. Parenteral Estrogens.- 4. Potency of Various Estrogens According to the Route of Administration.- III. Pharmacodynamic Effects of Oral and Non-oral Estrogen.- 1. On the Endometrium.- 2. On Bone.- 3. On Cardiovascular Risk Factors.- a) Acute Effects of Estradiol.- b) Chronic Effects of Estradiol.- C. Conclusion.- References.- 6: Kinetics and Toxicology of Estrogens and Antiestrogens.- Pharmacokinetics of Exogenous Natural and Synthetic Estrogens and Antiestrogens.- A. Natural Estrogens.- I. Analytical Methods.- II. Pharmacokinetics in Animals.- 1. Absorption.- 2. Distribution.- 3. Metabolism.- 4. Excretion.- III. Pharmacokinetics in Humans.- 1. Absorption.- 2. Distribution.- 3. Metabolism.- 4. Excretion.- IV. Comparison of Different Routes of Administration.- V. Other Estrogens.- 1. Conjugated Equine Estrogens.- 2. Estriol.- VI. Drug Interactions.- 1. Interaction with Progestins.- 2. Interaction of Estradiol with its Own Metabolism.- 3. Interaction of Estradiol with Other Drugs.- B. Synthetic Estrogens.- I. Analytical Methods.- II. Pharmacokinetics in Animals.- 1. Absorption.- 2. Distribution.- 3. Metabolism.- 4. Excretion.- III. Pharmacokinetics in Humans.- 1. Absorption.- 2. Distribution.- 3. Metabolism.- 4. Excretion.- IV. Comparison of Different Routes of Administration.- V. Drug Interactions.- 1. In Vitro.- a) Interaction with Progestins.- b) Interaction of EE with Its Own Metabolism.- 2. In Vivo.- a) Interaction with Progestins.- b) Interaction of EE with Its Own Metabolism.- c) Drugs Interfering with the Metabolism of EE.- d) Interaction with Anticonvulsant Drugs.- e) Interaction with Rifampicin.- f) Interaction with Antibiotics.- g) Interaction with Paracetamol.- h) Interaction with Grapefruit Juice.- i) Interaction with Ascorbic Acid.- j) Interference of EE with the Metabolism of Other Drugs.- C. Antiestrogens.- I. Analytical Methods.- II. Pharmacokinetics in Animals.- 1. Absorption.- 2. Distribution.- 3. Metabolism.- 4. Excretion.- III. Pharmacokinetics in Humans.- 1. Absorption.- 2. Distribution.- 3. Metabolism.- 4. Excretion.- IV. Special Populations.- 1. Influence of Age.- 2. Influence of Altered Liver and Kidney Function.- V. Drug Interactions.- References.- Toxicology of Estrogens and Antiestrogens.- A. General Aspects.- B. Toxicology of Estrogens.- I. Acute Toxicity.- II. Subchronic and Chronic Toxicity.- III. Genotoxi.- IV. Carcinogenicity.- V. Reproductive Toxicity.- 1. Effects on Fertility and Preimplantational Development.- 2. Embryotoxicity.- 3. Perinatal and Postnatal Effects.- C. Antiestrogens.- I. Acute Toxicity.- II. Subchronic and Chronic Toxicity.- III. Genotoxicity.- IV. Carcinogenicity.- V. Reproductive Toxicity.- References.- Estrogens and Sexually Transmitted Diseases.- A. Introduction.- B. The Impact of Hormonal Contraceptives.- I. Human Immunodeficiency Virus Infection.- II. Human Papilloma virus Infection.- III. Infection with Chlamydia trachomatis, Neisseria gonorrhea and Mycoplasma.- IV. Candida Albicans Infection.- V. Trichomoniasis.- C. The Impact of Hormonal Replacement Therapy.- D. Conclusion.- References.- 7: Clinical Application and Potential of Estrogens and Antiestrogens.- Hormonal Contraception.- A. History.- B. Types of Hormonal Contraceptives.- I. Progestogen-Only Contraceptives.- 1. Mini-pill.- 2. Depot -Progestogens.- II. Estrogen/Progestogen-Containing Contraceptives.- 1. Post -coital Pill.- 2. Ovulation Inhibitors.- C. Pharmacology of Contraceptive Steroids.- I. Pharmacology of Estrogens.- II. Pharmacology of Progestogens.- 1. Nortestosterone Derivatives.- 2. Progesterone Derivatives.- D. Mode of Action of Oral Contraceptives.- E. Pharmacokinetics of Oral Contraceptives.- I. Factors Influencing Efficacy.- II. Interaction of Oral Contraceptives with Drugs.- F. Use of Oral Contraceptives.- I. Choice of Oral Contraceptives.- II. Metabolic Effects of Oral Contraceptives.- III. Beneficial Effects of Oral Contraceptives.- IV. Risks and Side Effects of Oral Contraceptives.- 1. Minor Complaints during Intake of Oral Contraceptives.- 2. Fertility, Pregnancy and Lactation.- 3. Immune System.- 4. Genital Tract Infections.- 5. Respiratory Tract and Gingiva.- 6. Eyes and Ears.- 7. Skin.- 8. Gastrointestinal Tract Disease.- 9. Urinary Tract.- 10. Endocrine Effects.- 11. Neurological Diseases.- 12. Psychiatric Diseases.- 13. Physical Condition and Sports.- 14. Venous Complaints.- 15. Venous Thromboembolic Diseases.- 16. Stroke.- 17. Hyperten.- 18. Myocardial Infarction.- 19. Raynaud’s Syndrome.- 20. Diabetes Mellitus.- 21. Liver.- 22. Liver Tumors.- 23. Breast.- 24. Breast Cancer.- 25. Uterine Tumors.- 26. Cervical Neoplasi.- 27. Ovarian Tumors.- 28. Other Cancers.- References.- Hormone Replacement Inclnding Osteoporosis.- A. The Menopause.- I. Climacteric Complaints.- II. Estrogens and the Skeleton.- III. HRT, Serum Lipids and the Risk of Cardiovascular Disease.- IV. Estrogens and Neurodegenerative Diseases.- V. Selective Estrogen Receptor Modulators.- References.- Gynaecological Disorders.- A. Introduction.- B. Primary Amenorrhoea.- C. Secondary Amenorrhoea.- D. Bleeding Problems.- E. Anti-estrogens.- References.- Oncology.- A. Breast Cance.- I. Systemic Hormonal Treatment of Breast Cancer.- II. Tamoxifen.- III. Present Strategies.- 1. Adjuvant Therapy.- 2. Metastatic Therapy.- 3. Prophylaxis.- 4. Male Breast Cancer.- 5. Desmoid Tumours.- IV. Estrogen Hormone Receptors in Breast Cancer.- V. Second-Line Therapy.- 1. Aromatase Inhibitors.- 2. Evolution of Aromatase Inhibitors.- VI. Future Developments.- 1. Tamoxifen Analogue.- 2. Benzothiophene Derivatives.- 3. Steroidal “Pure” Anti-estrogens.- B. Ovarian Cancer.- I. Hormonal Involvement.- 1. Hormone Replacement Therapy.- 2. Oral Contraceptives..- 3. Tamoxifen.- C. Endometrial Cancer.- I. Hormonal Involvement.- 1. Hormone Replacement Therapy.- 2. Tamoxifen.- References.- Cardiology.- A. Introduction.- B. Epidemiological Association Between Oral Contraceptive Use and Thrombosis.- C. Oral Contraceptives and Hemostasis.- I. Oral Contraceptives and the Vessel Wall.- II. Oral Contraceptives and Platelets.- III. Oral Contraceptives and Coagulation.- 1. Clotting System.- 2. Fibrinolytic System.- a) Oral Contraceptives and Fibrinolysis.- IV. Oral Contraceptives and Molecular Markers of Hemostasis Activation.- D. Oral Contraceptives and Thrombophilia.- E. Summary.- References.- Urogenital Ageing and Dermatology.- A. Urogenital Aging.- I. Specific Functional Aspects of the Urogenital System.- II. Functional Changes Due to Age and Menopause.- III. Epidemiology of Urogenital Symptoms.- IV. Clinical Evaluation.- V. Treatment.- VI. Conclusion.- B. Dermatology.- I. Skin Composition.- II. Effects of Age and Estrogen Deficiency on the Skin.- 1. Epidermis.- 2. Dermis.- III. Effects of Estrogen Replacement Therapy.- IV. Conclusion.- References.- Geriatric Neurology and Psychiatry.- A. Introduction.- B. Estrogen and the Brain..- C. Estrogen, Mood, and Behavior.- D. Estrogen and Cognition.- E. Stroke.- F. Dementia.- I. Alzheimer’s Disease.- 1. Estrogen Impact on Alzheimer’s Disease: Possible Mechanisms.- 2. Estrogen and Alzheimer’s Disease Risk.- a) Alzheimer’s Risk: Strength of Association.- b) Alzheimer’s Risk: Estrogen and Apolipoprotein E.- c) Estrogen and Alzheimer’s Risk: Caveats.- 3. Estrogen and Alzheimer’s Disease Symptoms..- 4. Indirect Markers of Estrogen Exposure and Alzheimer’s Disease.- II. Multi-infarct Dementia.- G. Other Neuropsychiatric Disorders..- I. Migraine Headache.- II. Epilepsy.- III. Parkinson’s Disease and Other Movement Disorders.- IV. Multiple Sclerosis.- H. Conclusions.- References.- Estrogens and Antiestrogens in the Male.- A. Introduction.- B. Age-Related Changes of Estrogen Secretion.- C. Metabolism and Pharmacokinetics of the Estrogens in the Male.- D. Genitourinary System.- I. What Can We Learn from the ERa Knock-Out (ERKO) Mice?.- II. Gonads.- III. Epididymis.- IV. Prostate.- E. Mammary Gland.- F. Liver.- I. Estrogens.- II. Antiestrogens.- G. Bone.- H. Cardiovascular System.- I. Central Nervous System.- I. What Do We Know About Gender Differences Concerning Cerebral Blood Flow?.- II. What Do We Know About the Connection between the Serum Levels of Endogenous Estrogen and Certain CNS Functions in Men?.- III. What Do We Know about the Influence of Exogenous Estrogen on CNS Functions in Men?.- J. The Influence of Environmental Estrogens (Xenoestrogens) on the Fertility of Men.- K. Regimens for Estrogen and Antiestrogen Treatment in Men.- I. Treatment of Prostate Cancer with Estrogens.- II. Estrogen Replacement in Men.- III. Male Contraception with Estrogens.- IV. Treatment of Male-to-Female Transsexuals with Estrogens.- L. The Therapeutic Value of Antiestrogens and Aromatase Inhibitors in Men.- M. The Concept of Non-Feminizing Estrogens.- References.- 8: Comparative Endocrinology.- Comparative Aspects of Estrogen Biosynthesis and Metabolism and the Endocrinological Consequences in Different Animal Species.- A. Evolution of Estrogens.- B. Comparative Biochemistry.- I. Estrogen Biosynthesis.- II. Estrogen Receptor and Signal Transduction.- III. Elimination.- C. Evolution of Estrogen Functions.- I. Oviparous Vertebrates.- II. Viviparous Eutherian MammaliaiPlacentalia.- 1. Estrus.- 2. Embryonic Pregnancy Signaling.- 3. Placental Estrogens.- 4. Estrogens in Males.- 5. Metabolic, Anabolic and Other Secondary Features..- References.- Therapeutic Use of Estrogens in Veterinary Medicine.- A. Introduction.- B. Pharmacokin.- C. Undesirable Effects, Interactions, and Toxicity.- D. Indications.- E. Dosage.- F. Antiestrogens.- References.- 9: Estrogens, Antiestrogens, and the Environment.- Environmental Estrogens.- A. Introduction and Perspective.- B. Initial Identification of Environmental Estrogens.- I. Phytoestrogens.- II. Mycoestrogens.- III. Xenoestrogens.- C. Structures and Sources of Major Prototype Environmental Estrogens.- I. Phytoestrogens.- 1. Isoflavones.- 2. Coumestans.- 3. Lignans.- II. Mycoestrogens.- III. Xenoestrogens.- 1. Pesticides and Agricultural Chemicals.- 2. Halogenated Aromatic Hydrocarbons.- 3. Commercially Used Phenols and Related Compounds.- D. Mechanisms of Action.- I. Receptor Interactions.- II. Gene Expression.- 1. Phytoestrogens.- 2. Mycoestrogens.- 3. Xenoestrogens.- III. Cell Growth and Proliferation.- 1. The In Vivo Uterotrophic Response to Environmental Estrogens.- 2. Proliferation of Estrogen-Sensitive Cancer Cell Lines.- 3. Angiogenesis.- IV. Development and Differentiation.- 1. Effects on Female Sexual Differentiation.- 2. Effects on Uterus, Vagina and Ovary.- 3. Effects on Mammary-Gland Differentiation and Carcinogenesis.- 4. Effects in Males.- E. Human Exposures, Epidemiology and Potential Health Effects.- I. Organochlorines and the Incidence of Breast Cancer.- II. Phytoestrogens and Prevention of Breast Cancer.- III. Phytoestrogens and Prostate Cancer.- IV. Cardiovascular Disease and Osteoporosis.- V. Fertility and Reproductive Health.- F. Conclusion.- References.