Hormonal Treatments in Gynaecology

Contents
Preface
Acknowledgments
Chapter 1
Estrogens
Introduction
Biosynthesis of Steroid Hormones and Steroidogenesis
Sex Hormone Steroidogenesis
Theca Cells
Granulosa Cells
Luteal Cells (Progesterone Biosynthesis)
Regulation of Synthesis and Secretion: Female Genital Cycle
Estrogen Metabolism
Normal Estrogen Levels during a Woman’s Lifetime
Mechanisms of Action of Estrogens
Activation of ER
Signaling Pathways
Location of Receptors
Estrogen Target Organs and Actions
Estrogenic Actions on the Female Reproductive System
Ovary
Uterus
Breast
External Genitalia
Estrogenic Actions on Other Systems
Cardiovascular System
Lipid Metabolism
Skeletal System
Urinary System
Central Nervous System
Effects of Estrogenic Deprivation
Clinical Applications of Estrogens
Available Estrogens
Contraception and Estrogens
Dysfunctional Uterine Bleeding and Estrogens
Severe or Prolonged Uterine Bleeding and Estrogens
Intrauterine Adhesions and Estrogens
Late Puberty and Estrogens
Other Gynecological Pathologies and Estrogens
Spontaneous Primary Ovarian Insufficiency and Estrogens
Menopause and Estrogens for Hormone Replacement Therapy (HRT)
Short-Term Symptoms of Menopause
Long-Term Menopausal Changes
Hormone Replacement Therapy: Risks and Benefits
Available Estrogens for HRT
Systemic Estrogens
Oral Estrogens for HRT
Efficacy/Potency
Transdermal Estrogens for HRT
Oral-Transdermal Dose Equivalence
Vaginal Estrogens at High or Medium Doses
Local/Topical Estrogens
Estrogen’s Treatment of Menopausal Symptoms
Treatment of Hot Flashes
Treatment of Genitourinary Symptoms
Contraindications to Estrogens
Conclusion
References
Chapter 2
Progestins
Introduction
Metabolism and Mechanism of Action
Classification of Progestins
1. Progestogens Structurally Related to Progesterone
2. Progestogens Structurally Related to Testosterone
Route of Administration
Threatened Abortion
Threatened Preterm Labor
Hypothalamic Amenorrhea
Abnormal Uterine Bleeding
Endometriosis
Progestin-Only Contraception
Emergency Contraception
Myomas
Vulvar Dystrophies
Menopausal Hormonal Therapy
Conclusion
References
Chapter 3
Combined Hormonal Contraceptives
1. Introduction
2. Characteristics of the Contraceptive Method
3. Forms of Administrations
3.1. Oral Administration
3.2. Parenteral
3.3. Vaginal
3.4. Transdermal Pathway
4. Effectiveness
5. Clinical Applications and Beneficial Effects
5.1. Control of the Menstrual Cycle
5.2. Dysmenorrhea
5.3. Endometriosis
5.4. Pelvic Inflammatory Disease
5.5. Treatment for Hyperandrogenism: Acne, Seborrhea and Hirsutism
5.6. Osteoporosis
5.7. Decreased Risk of Cancer
5.7.1. Endometrial Cancer
5.7.2. Ovarian Cancer
6. Side Effects
6.1. Minor Adverse Effects
6.1.1. Nausea and Vomiting
6.1.2. Weight Gain
6.1.3. Mastalgia
6.1.4. Headaches
6.1.5. Sexual Inappetence
6.1.6. Acne
6.1.7. Mood Swings or Depression
6.1.8. Dysfunctional Bleeding
6.1.9. Amenorrhea and Amenorrhea Post Pill
6.2. Major Adverse Effects
6.2.1. Venous Thromboembolism
6.2.2. Blood Pressure
6.2.3. Acute Myocardial Infarction
6.2.4. Acute Stroke
6.2.5. Alteration of the Lipid Profile
6.2.6. Gastrointestinal Alterations
6.2.7. Breast Cancer
6.2.8. Cervical Cancer
7. Contraindications for Use
Conclusion
References
Chapter 4
Selective Estrogen Receptor Modulators
1. Introduction
2. Mechanism of Action and Metabolism of Selective Estrogens Receptor Modulators
2.1. Estrogen Receptors and Mechanism of Action
2.2. Biological Activity of Hormones and Agonists
2.3. Selective Modulators of the Estrogen Receptors
2.4. Resistance to Selective Estrogen Modulators
3. Types, Metabolism and Mechanism of Action of Selective Modulators of Estrogen Receptors
3.1. Tamoxifen
3.2. Raloxifene
3.3. Ospemifene
3.4. Bazedoxifene
3.5. Clomifene Citrate
4. Types, Clinical Applications and Indications of Selective Modulators of Estrogen Receptors
4.1. Prevention of Breast Cancer
4.1.A. Post-Menopausal Women
4.1.B. Premenopausal Women
4.2. Adjuvant Treatment of Breast Cancer
4.2.A. Premenopausal
4.2.B. Post-Menopausal
4.3. Treatment of Metastatic Breast Cancer with Positive Hormonal Receptor
4.4. Treatment of Genitourinary Syndrome of Menopause
4.5. Prevention and Treatment of Osteoporosis
4.5.A. Raloxifene
4.5.B. Lasofoxifene
4.5.C. Tamoxifen
4.5.D. Bazedoxifene
4.6. Menopausal Symptoms
4.7. Ovulation Induction
5. Side Effects of Selective Estrogens Receptor Modulators
5.1. Other Serm Related Side Effects
General
Venous Thromboembolism
Arterial Thromboembolism
Genital Pathology
5.2. Side Effects of Tamoxifen
Teratogenic and Fertility Effects
General
Venous Thromboemolism
Arterial Thromboembolism
Uterine Pathology
Uterine Bleeding
Polyps
Endometrial Hyperplasia
Endometrial Cancer
Sarcoma and Uterine Carcinosarcoma
Conclusion
References
Chapter 5
Selective Progesterone Receptor Modulators
Introduction
Different Types of Selective Progesterone Receptor Modulators
Metabolism and Mechanism of Action of Selective Progesterone Receptor Modulators
The Molecular Mechanism of Action and Metabolism of SPRMs
Mifepristone
Ulipristal Acetate
Clinical Applications of Selective Progesterone Receptor Modulators: Indications
SPRMs as Contraceptives
SPRMs as Emergency Contraception: (For Further Information See Chapter 2: Progestins)
SPRMs for Termination of Pregnancy
Mifepristone for Termination Pregnancy at the First Trimester
Mifepristone for Termination Pregnancy at the Second Trimester
SPRM for the Treatment of Ectopic Pregnancy
The SPRMs in the Treatment of Endometriosis
Mifepristone
Ulipristal Acetate
SPRMs for the Treatment of Fibroids
SPRMs for Prolonged Uterine Bleeding
SPRMs and Breast Cancer
SPRM and Endometrial Cancer
Side Effects and Contraindications of Selective Progestin Receptor Modulators
Contraindications of Mifepristone
Side Effects of Mifepristone
Contraindications of Ulipristal Acetate
Side Effects of Ulipristal Acetate
Long-Term Treatment Safety of Selective Progestin Receptor Modulators
Hepatotoxicity
Ovarian Cysts
Prolactin Levels
Bone Mineral Density
Conclusion
References
Chapter 6
GnRH Agonists and Antagonists and Their Therapeutic Use in Gynaecology
Introduction
Mechanism of Action and Metabolism
GnRH
GnRH Agonists
GnRH Antagonists
Therapeutic Use of GnRH Agonists and Antagonists
Fertility
Uterine Fibroids (Leiomyomas)
Contraception
Endometriosis/Adenomyosis
Breast Cancer
Endometrial Cancer
Ovarian Cancer
Management of Transgender and Gender-Diverse Children and Adolescents
Contraindications
Conclusion
References
Chapter 7
Aromatase Inhibitors in Gynaecology
Introduction
Mechanism of Action
Types of Aromatase Inhibitors
Clinical Use in Gynecology
Breast Cancer
Adjuvant Therapy
Metastatic Disease
Prevention
Uterine Fibroids
Endometriosis
Adenomyosis
Anovulation
Endometrial Carcinoma
Side Effects and Toxicity
Bone-Loss
Musculoskeletal Pain
Cardiovascular Disease
Conclusion
References
Chapter 8
Androgens and Dopaminergic Agonists in Gynaecology
Androgens
Introduction
Androgen Production
Androgen Deficiency
Body Composition, Muscle, and Bone Effects
Lipids and Cardiovascular Effects
Breast Tissue, Endometrium, and Fertility
Androgen Therapy in Women
Testosterone Products for Women
Adverse Effects and Risks of Testosterone Therapy in Women
Monitoring Patients Receiving Testosterone Therapy
DHEA Therapy in Women
Conclusion
Dopaminergic Agonists
Introduction
Types of Dopamine Agonists
Efficacy of Dopaminergic Agonists Therapy
Adverse Effects of Dopaminergic Agonists Therapy
Dopaminergic Agonist Therapy in Women
1. Hyperprolactinaemia
Indications for Treatment
Microadenomas
Macroadenomas
Ovulation Induction in Women with Hyperpolactinaemia and Gestational Desire
Adenomas during and after Pregnancy
Idiopathic Hyperprolactinaemia
Termination of Dopaminergic Agonist Therapy in Patients with Hyperprolactinaemia
2. Prevention of Ovarian Hyperstimulation Syndrome
3. Suppression of Lactation
Conclusion
References
Chapter 9
Hormonal Treatments in Fertility
Introduction
Progesterone
How to Use Progesterone
Estrogens
How to Use Estrogens
Ovulation Inductors
Clomiphene Citrate
How to Use Clomiphene Citrate
Aromatase Inhibitors
How to Use Aromatase Inhibitors
Gonadotropins
How to Use Gonadotropins
Dosing
Pituitary Suppressors
GnRh Agonists
How to Use GnRh Agonists
GnRh Antagonists
How to Use GnRh Antagonists
Ovulation Triggers
Human Chorionic Gonadotropin
How to Use hCG as an Ovulatory Trigger
Recombinant LH
How to Use Recombinant LH
Conclusion
References
Editors’ Contact Information
Index
Blank Page
Blank Page