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Endocrinology in Obstetrics & Gynecology Suvarna S Khadilkar

PART 1: FRONTIERS IN ENDOCRINOLOGY
1:Hypothalamus
- Structural Anatomy2
- Output3-5
  - Neural Projections
- Neuroendocrine Function
- Hypothalamic-Adenohypophyseal (Anterior Pituitary) Axis
- Hypothalamic-Neurohypophyseal (Posterior Pituitary) Axis
- Clinical Relevance
  - Hypothalamic-adenohypophyseal (Anterior Pituitary) Axis
- Hypothalamic Dysfunction
- Summary
2:Pituitary Gland
- Anatomy and Physiology of the Pituitary Gland1-3
- Functions
- Histology1
- Pituitary Disorders
3:Pineal Gland
- Introduction
- Anatomical Relations of Pineal Gland
- Neural Connections of Pineal Gland (Figure 2)
- Histology
- Type of Cell and Hormones
- Biosynthesis of Melatonin (Fig. 3)
- Physiology
- Function of Melatonin
- Applied Physiology
- Pathology
4:Ovaries
- Anatomical Considerations
  - Histology
  - Corpus Luteum
- Physiology
- Functions of Hormones Produced in the Ovary
  - Pathological Involvement of the Ovary
- Conclusion
5:Testis
- Introduction
- Anatomy and Physiology of the Male Reproductive System (Fig. 1)
  - Hypothalamus–pituitary–gonadal Axis (Fig. 2)
- Testis
- Spermatogenesis—Stages
- Epididymis
- Vas Deferens
- Ejaculate
6:Thyroid Gland
- Applied Anatomy and Anatomical Relations1
- Histology
- Physiology2 (Fig. 3)
- Thyroid Function Tests
7:Parathyroid Gland
- Anatomy
- Histology
- Physiology
- Pathology
  - Hypoparathyroidism
  - Hyperparathyroidism
- Summary
8:Adrenals and the Kidneys
- Morphology: The Adrenal Cortex and Adrenal Medulla
- Adrenal Histology and Physiology
  - Action and Function of the Adrenal Medulla Hormones1,2
    - Effect of Epinephrine and Norepinephrine
    - Effect of Dopamine
- Action and Function of Adrenal Cortex Hormones1,2
- Pathological Involvement, Hypersecretion and Effects of Glucocorticoids on Body1
- Pathological Involvement, Hypersecretion and Effects of Mineralocorticoids on Body1,2
- Hyposecretion of Adrenal Hormones
- Kidneys
  - Anatomy of Kidneys
9:Pancreas
- Anatomy of Pancreas
- Histomorphology of Islets
- Endocrine Physiology
  - Insulin
- Pathophysiology of Insulin Secretion
  - Diabetes
  - Insulin Excess
- Insulin Preparations
- Glucagon
  - Pathophysiology of Glucagon Secretion
- Somatostatin
  - Pathophysiology of Somatostatin Secretion
- Pancreatic Polypeptide
  - Pathophysiology of PP Secretion
10:Human Skin and Adipose Tissue as Endocrine Units and Exercise Physiology
- Introduction
- Distribution of Adipose Tissue
- Differences between White and Brown Adipose Tissues (Fig. 1)
- Functions of Adipose Tissue
  - Metabolic, Endocrine and Paracrine Functions
- Leptin
- Major Influences on Leptin Expression in Human Adipose Tissue
- Functions of Leptin
- Adiponectin
- Interleukin-6
  - Pathophysiology
- Tumor Necrosis Factor (TNF) Alpha
  - Mechanism of TNFs Metabolic Effects
  - Functions of TNF Alpha
- Plasminogen Activator Inhibitor-1
  - Functions
- Macrophage and Monocyte Chemoattractant Protein (MCP)
  - Functions of MCP
- Adipsin and Acylation Stimulating Protein (ASP)
  - Functions of ASP
- Resistin
  - Functions of Resistin
- Proteins of Renin Angiotensin System (RAS)
  - Functions of RAS
- Enzymes Involved in Metabolism of Sex Steroids
- Enzymes Involved in the Metabolism of Glucocorticoids
- Exercise Physiology40
- Conclusion
11:Placenta and Hormonal Changes in Normal Pregnancy
- Anatomy and Development of Placenta1,2
- Anatomy at Term
- Physiology of Placenta
  - Uteroplacental Circulation
- Functions of Placenta
- Conclusion
12:Physiology of Lactation
- Introduction
- Anatomy
- Physiological Basis
- Synthesis and Secretion of Milk Components
- Regulation of Milk Production
- Summary
PART 2: ENDOCRINOLOGY IN CLINICAL PRACTICE
13:Normal and Abnormal Puberty
- Normal Puberty
  - Definition
  - Determinants of Age at Onset of Puberty and Global Trends
- The Age Limits for Normal Pubertal Development
  - Changes in the Secondary Sexual Characteristics in Puberty
  - Physiology of Onset of Puberty
- Abnormal Puberty
- Precocious Puberty
- Take Home Message
14:Disorders of Sex Development
- Introduction
- Revised Nomenclature
  - Clinical Features
- Investigations
  - Imaging
- Diagnosis
  - Gender Assignment in Newborn
- Management
  - Surgical Management
  - Surgical Procedures
- Gonadectomy
- Hormonal Replacement Therapy
- Psychosocial Management
  - Research and Future Directions in Management
- Conclusion
- Take Home Message
15:Abnormalities of Growth and Pubertal Development in Adolescence
- Physical Changes in Girls During Puberty
- Abnormalities of Growth and Pubertal Development in Adolescence
- General Approach to an Adolescent Girl with Pubertal Problems
- Short Stature
- Evaluation of a Short Adolescent
- Tall Stature
- Obesity
- Evaluation of an Obese Adolescent
- Hyperandrogenism and PCOS
  - Polycystic Ovary Syndrome
- Precocious Puberty
- Evaluation of Girls with Early Puberty
- Delayed Puberty
- Evaluation of Girl with Delayed Puberty
  - Primary Amenorrhea
  - Factors that Help in Diagnosis11
- Evaluation of Girl with Amenorrhea
- Take Home Message
16:Disorders of Adrenal Gland
- Introduction
- Disorders of Adrenals Cortex
- Hyperfunction of Adrenals
- Management
  - Surgery for Adrenal Adenoma
  - Bilateral Adrenalectomy
- Aldosteronism
- Hypofunction of Adrenal Cortex
- Hypoaldosteronism
- Congenital Adrenal Hyperplasia (Fig. 4)
- DHEA and Adrenal Imbalance
  - DHEA from Adrenals and Ovary
- Function of DHEA and DHEAS
  - Tumors of Adrenal Medulla6
  - Pheochromocytoma
- Summary
- HVA VMA Metanephrine
- Take Home Message
17:Hirsutism
- Introduction
- Types of Disorders and Causes
- Assessment of Hirsutism
- Diagnosis and Differential Diagnosis
- Treatment
  - Cosmetic Approach
- Medical Management
  - Medical Therapy for Hirsutism may be Directed at Several Levels
- Take Home Message
18:Sex Reassignment Therapy
- Sex Reassignment Therapy for Transition from Female to Male
  - Hormone Regimen for Female to Male2
  - Expected Effects of Therapy
- Transdermal Testosterone
- Health Risks and Side Effects of Testosterone
- Side Effects of Testosterone3
- Hormonal Management of a Child Born with Ambiguous Genitalia
- Take Home Message
19:Amenorrhea: Clinical Evaluation and Treatment
- Introduction
- Definitions of Amenorrhea
- Causes of Amenorrhea
  - Physiological
  - Pathological
- Clinical Features
- Evaluation in Primary Amenorrhea
- Specific Conditions Causing Primary Amenorrhea and Management in Brief
- Disorders of Compartment I
- Disorders of Compartment II
  - Polycystic Ovarian Syndrome
  - Premature Ovarian Failure
- Primary Ovarian Failure (Hypergonadotropic Hypogonadism)
  - Masculinizing Ovarian Tumor
- Pituitary or Compartment III Factors
  - Pituitary Adenoma/Prolactinoma
  - Sheehan Syndrome
- Compartment IV Defects
  - Eating Disorders
  - Management of Eating Disorders
- Take Home Message
20:Prolactin Disorders
- Introduction
- Epidemiology
- Causes of Hyperprolactinemia
- Prolactinoma
- Malignant Prolactinoma
- Take Home Message
21:Miscellaneous Pituitary Diseases
- The Pituitary Incidentaloma
- Gonadotropin-producing Pituitary Tumors
- GH-secreting Pituitary Adenoma (Acromegaly)
- ACTH-secreting Tumors (Cushing's Disease)
- Thyrotropin (TSH)-secreting Tumors
- Sheehan's Syndrome
- Lymphocytic Hypophysitis
- Vasopressin
- Oxytocin
- Empty Sella Syndrome
- Causes of Pituitary Failure
  - Trauma
- Take Home Message
22:Heavy Menstrual Bleeding
- Introduction
- Causes of HMB
  - Type of Disorder
  - Clinical Features
- Management
  - Puberty Menorrhagia
- Estrogen:
  - Progesterone - Other Routes – MIRENA
- Conclusion
- Take Home Message
23:Polycystic OvarianSyndrome
- Diagnosis
- The Insulin Hypothesis
- Clinical Evaluation of PCOS
- Investigations
- Management of PCOS
- Other Drugs Used in the Management of PCOS
- Conclusion
- Take Home Message
24:Ovulation InductionProtocols for Anovulation, PCOS, IUI and ART Cycles
- Introduction
- Clinical Features
- Investigations
- Differential Diagnosis
- Ovulation Induction
- Risks and Complications with Clomiphene Treatment
- Aromatase Inhibitors—Letrozole and Anastrozole70-72
- Gonadotropins for Ovulation induction
  - Indications
  - Gonadotropin Preparations
- OI Protocols using Gonadotropins
- Kato Protocol73
- Induction of Follicular Maturation and Ovulation
  - Timing of Follicular Maturation
  - Side Effects
- Adjuvants Drugs to Gonadotropins
- Down Regulation with Ovarian Steroids
- Polycystic Ovary Syndrome
- Discussion
  - Future Directions
  - Oral LMW FSH and LH Agonists
- Conclusion
- Take Home Message
25:Luteal Phase Support
- Introduction
- Luteal Phase Support Agents
- Progesterone Supplementation
  - Types of Progesterone
- Natural Progesterone: Routes of Administration
- hCG and Luteal Support
- Adjunct Therapy
- LPS in Various Protocols
  - Antagonist Cycles
  - LPS after Ovulation Induction and Intrauterine Insemination
- LPS: Cochrane Review
  - Michelle van der Linden (2011)15
- Conclusion
- Take Home Message
26:Thyroid and Infertility
- Introduction
- Estrogens and Thyroid Hormones
- Thyroid Disorders
- Hypothyroidism and Infertility
- Subclinical Hypothyroidism and Infertility
- Autoimmune Thyroid Disease and Infertility
- AITD and Pregnancy Outcome After Art
  - Recent Recommendations of American Association of Clinical Endocrinologists (AACE) and American Thyroid Associatio (ATA)16
- Hyperthyroidism and Infertility
- Thyroid Function after Controlled Ovarian Hytperstimulation (COH)
- Take Home Message
27:Endocrinology in Clinical Practice: Male Infertility
- Hormonal Control of Spermatogenesis
- History
- Physical Examination
- Semen Analyis (Table 1)
- Causes of Male Infertility (Table 2)
  - Sexual Dysfunction
  - Pituitary Dysfunction
- Prolactinoma
- Take Home Message
28:Hormonal Management of Endometriosis
- Introduction
- Management
  - Medical Management of Endometriosis
  - Hormonal Treatment
- Oral Contraceptive Pill
- Progestins
- Conclusion
- Take Home Message
29:Premature Ovarian Failure
- Anatomy and Embryology
- Histology
- Physiology
  - Endocrine Regulation of Folliculogenesis
- Normal Range of Blood Levels5
- Pathological Involvement
- Hyposecretion and Effects on Body
- Hypersecretion and Effects on Body
- Premature Ovarian Failure
- Clinical Features
- Investigations
- Screening for Autoimmunity
  - Genetic Analysis
  - Risk Factors
- Management of POF
- Conclusion
- Take Home Message
30:Ovarian Transplant: An Overview
- Introduction
- Historical Aspects
  - How do ovaries respond to transplantation?
- Indications
- Surgical Techniques
  - Vascular Ovarian Transplantation
- Vascular Orthotopic Ovarian Transplant
  - Avascular Ovarian Tissue Grafting or Ovarian Implants
- Take Home Message
31:Combined Hormonal Contraceptives
- Introduction
- History of Hormonal Contraceptives
- Combined Oral Contraceptive Pills (Table 1)
  - Mechanism of action
- Cyclic Combined Pills
  - Extended/Tailored Regimes
- Starting a COC Regimen
- Advantages of Low-dose COCs
  - Disadvantages of Low-dose OCs
- Combined Vaginal Rings
- Transdermal Contraception
  - Types
- Combined Injectable Contraceptives
- Conclusion
- Take Home Message
32:Progesterone-only Contraception: Oral, Injectable, Implants, Intrauterine Systems
- Introduction
  - First Generation
  - Second Generation
  - Third Generation
  - Newest Progestins
- Progestogen-only Contraceptive Pill (POP) (Mini Pills)
- Mechanism of Action
- Effectiveness
- Advantages of POPs
- Disadvantages of POPs
- Evaluation and Patient Selection
- Counseling
  - Warning Signs
- Conclusion
- Introduction
- Mechanism of Action
- Contraceptive Efficacy
  - Advantages of Progestin Injectables
  - Side Effects of Progestin Injectables
- Contraindications
- Evaluation
- Noncontraceptive Benefits
  - Timing of Initiation of Use
- Options Available
  - Timing of Repeat Injections
  - Warning Symptoms
  - Counseling Tips
- Conclusion
- Introduction
  - Types of Implant
  - Benefits of Implantable Contraceptives
- Mode of Action
- Duration of Use
- Effectiveness
- Indications
- Timing of Insertion
- Switching from Another Method of Contraception
- Insertion and Removal
  - Follow-up
  - Signs and Symptoms Requiring Medical Attention
  - Advantages
  - Disadvantages
- Counseling
- Conclusion
- Introduction
  - Antifertility Action of Progesterone Releasing IUDs26
- Mechanism of Action
  - Candidates for LNG-IUS
- Contraindications for LNG–IUS
- Patient Counseling
  - Patient Evaluation
- Insertion
- Continuation and Follow up
- Effectivenes
  - Side Effects
- Conclusion
- Take Home Message
33:Emergency Contraception
- Introduction
- Indications
  - Contraceptive Accidents Include
- Types of EC and their Mechanism of Action
  - High Dose Estrogens
  - Estrogen Progestogen Combination: Yuzpe Method
- Levonorgestrel Alone
- Anti-progestogen Mifepristone
- Other Methods Tried
  - Danazol
  - Intrauterine Contraceptive Devices (IUD)
- Mechanism of Action of Hormonal EC
  - Management of a Request for EC
  - Follow-up
- Problems in Clinical Practice
- Ethical, Legal and Regulatory Aspects of EC
- Take Home Message
34:Endocrinology of Medical Abortion
- Introduction
- Endocrinology of Early Pregnancy
  - Human Chorionic Gonadotropin (HCG)
- Progesterone
- Estradiol
- IGFBP-l
- Endocrine Alteration Associated with Termination of Early Pregnancy
  - hCG
- Progesterone
  - Oestradiol
  - IGFBP-l
- Regulation of IGFBP-l
  - Compounds used for Medical Abortion and their Mechanisms of Action
- Uterotonics
- Prostaglandin Analogues
  - Sulprostone
- Gemeprost
- Misoprostol
- Uterine Contractility
- Antimetabolites
- Antiprogesterones
- Mifepristone
  - Clinical Course of Medical Abortion Induced with a Combination of Mifepristone and Misoprostol as Reflected by Selected Endocrine Markers
- Clinical Use of Medical Abortion
- Take Home Message
35:Thyroid Disorders in Pregnancy
- Introduction
  - Physiological Changes in Pregnancy
    - Iodine Requirements
    - Effects of hCG on Thyroid Function
- Thyroid Tests in Pregnancy
- Types of Disorders and Causes (Table 2)
- Take Home Message
36:Gestational Diabetes Mellitus
- Introduction
- Definition
- Prevalence
- Diagnosis
- Selective Versus Universal Screening
- Gestational Age at Screening
- Pathophysiology of Gestational Diabetes
  - Physiology in Normal Pregnancy
  - Physiology in Gestational Diabetes Mellitus
- Risk Factors
- Complications of GDM
- Maternal and Fetal Monitoring in GDM
  - Ultrasonography
  - Doppler Studies
- Monitoring Glycemic Control
  - Target26
- Treatment
- Medical Nutrition Therapy
  - Diet
  - Exercise
- Pharmacotherapy
- Antepartum Fetal Surveillance
- Postpartum
- Early Postpartum Care
- Take Home Message
37:Miscellaneous Endocrinopathies during Pregnancy
- Introduction
- Adrenal Disorders in Pregnancy
- Congenital Adrenal Hyperplasia (CAH) and Pregnancy
  - Management
- Treatment
- Cushing Syndrome with Pregnancy
- Clinical Features
- Pheochromocytoma in Pregnancy
- Clinical Features
- Take Home Message
38:Endocrinological Factors in Recurrent Pregnancy Loss
- Introduction
- Thyroid Disorders
  - Management
- Diabetes Mellitus
  - Management
    - Preconception
    - Pregnancy
- PCOS
  - Management
- Luteal Phase Deficiency
  - Management
- Take home message
39:Obesity Proneness at Transitional Phases in Women's Life
- Introduction
  - Sexual Dimorphism in Obesity, Body Fat and Fat Distribution
- Sexual Dimorphism in Adipose Tissue Metabolic Function
- Conclusion
- Take Home Message
40:Menopause: Physiology and Symptomatology
- Introduction
- Evolution of Menopause
- Classification and Definitions
  - Staging System
- Age of Menopause
- Physiology of Menopause17
- Ultrasound and Endocrine Markers
- Early Symptoms of Menopause
- Long-term Consequences of Estrogen Deficiency
  - Cardiovascular Diseases
- Osteoporosis5
- Treatment
- Conclusion
- Take Home Message
41:Management Options in Menopause
- Introduction
- Menopausal Health Trends
- Symptoms and Long-term Consequences
- Management (Flowchart 1)
- Nonhormonal Therapy
- Hormone Therapy
- Conclusion
- Take Home Message
42:Menopausal Hormone Therapy: An Update
- The WHI Trial
- Vasomotor Symptoms
- Urogenital Atrophy
- Osteoporosis
- Cardiovascular Disease
  - MHT and Cancer
- Breast Cancer
- Endometrial Cancer
- Alzheimer's Disease
  - What does current evidence say?
- Drugs and Formulations in MHT
- Side effects Associated with Estrogen and Progesterone
- Profile of an Ideal Hormone Therapy
- Other Hormones
  - Tibolone
    - Specific Indications for Tibolone
- SERMS: Raloxifene
- Take Home Message
43:Osteoporosis: Risk Factors, Diagnosis and Assessment of Fracture Risk
- Introduction
- Causes and Risk Factors
  - Causes
    - Primary Osteoporosis
    - Secondary Osteoporosis
  - Risk Factors for Osteoporosis
- Screening for Osteoporosis and Assessment of Fracture Risk
- Conclusion
- Take Home Message
44:Prevention and Management of Osteoporosis
- Prevention of Osteoporosis
- Dietary Measures
  - Exercise
- Pharmacologic Therapy
- Parathyroid Hormone
- Calcitonin
  - Denosumab
- Hormone Replacement Therapy
- Other Agents
- Physical Therapy
- Occupational Therapy
- Take Home Message
45:Sarcopenia in Women
- Introduction
- Classification
- Hormones
- Clinical Features
- Investigations
- Differential Diagnosis
  - Cachexia
  - Therapy
- Conclusion
- Flow Diagram
- Take Home Message
46:Hormones and Breast Cancer
- Introduction
  - History
- Pathophysiology
- Biological Effect of Estrogen on Breast Tumors
- Estrogen Receptor
- Principle of Hormonal Treatment
- Clinical Use
  - Drugs: Indication, Dose, Adverse Effects and duration of use
  - Aromatase Inhibitors (AI): Letrozole, Anastrozole, Exemestane
- Principles of Hormone Treatment in Breast Cancer
- Development of Hormonal Resistance
- Future
- Take Home Message
47:Hormones and Cancer
- Hormones and Cancers
- Endometrial Carcinoma
- Risk Factors
- Tamoxifen and Endometrial Carcinoma
  - Hormone Replacement Therapy and Endometrial Carcinoma
- Oral Contraceptive Pills and Endometrial Cancer
- Hormonal Treatment for Endometrial Carcinoma
- Role of Hormone Replacement Therapy after Endometrial Cancer Treatment
- Recommendations19
- Hormones and Ovarian Carcinoma
- Risk Factors for Ovarian Carcinoma
- Hormone Replacement Therapy and Risk of Ovarian Carcinoma
- Hormone Replacement Therapy After Ovarian Cancer Treatment
- Recommendations
- Hormones and Cervical Cancer
- OC Pills and Cervical Cancer
- The Possible Postulated Mechanism
- Hormone Replacement Therapy and Risk of Breast Cancer
- Conclusions
- Take Home Message
48:Hormones and Ovarian Cancer
- Introduction
- Hormonally Active Ovarian Tumors
- Sex Cord Stromal Tumors
- Granulosa Cell Tumors
- Thecomas
- Sertoli Leydig Cell Tumors
- Sex Cord Tumors with Annular Tubules (SCTAT)
- Gynandroblastoma
- Steroid Cell Neoplasms/Lipid Cell Neoplasms
- Other Hormonally Active Ovarian Tumors
- Protective and Detrimental Effects of Hormones on Ovarian Cancer
- Take Home Message

INDEX

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Chapter Notes