Endometriosis and Adenomyosis: Global Perspectives Across the Lifespan

Foreword
Foreword
Foreword
Preface
Contents
Contributors
Part I: Endometriosis: An Overview
	1: A History of Endometriosis
		1.1	 Introduction
		1.2	 The Identification of Adenomyoma
		1.3	 Adenomyosis and Endometriosis
		1.4	 Identifying the Various Phenotypes of Endometriosis
			1.4.1	 The Ovarian Endometrioma
			1.4.2	 Deep Endometriotic Nodules
			1.4.3	 Superficial Peritoneal Lesions
		1.5	 The Work of Sampson
		References
	2: Global Epidemiological Data on Endometriosis
		2.1	 Overview
		2.2	 The Diagnosis of Endometriosis and the Dilemma for Epidemiology
		2.3	 Individual, Social and Medical Determinants of an Endometriosis Diagnosis
			2.3.1	 Individual Determinants of Diagnosis
			2.3.2	 Symptoms
			2.3.3	 Social and Medical Constructions of Endometriosis
			2.3.4	 Socio-economic, Cultural and Political Context
		2.4	 Epidemiology of Endometriosis
			2.4.1	 Incidence
			2.4.2	 Prevalence
				2.4.2.1	 Hospital/Clinic Samples
				2.4.2.2	 General Population Samples: Hospital Records/Insurance Claims Databases
				2.4.2.3	 General Population Samples: Self-Reported Endometriosis
				2.4.2.4	 Geographical Variations in Prevalence
				2.4.2.5	 Is the Prevalence of Endometriosis Increasing?
			2.4.3	 The Epidemiology of Endometriosis: Where to Next?
				2.4.3.1	 Endometriosis Diagnosis: Stages, Subtypes or Syndrome?
		References
	3: Pathogenesis of Endometriosis: Theories of the Cells of Origin and Methods of Dissemination
		3.1	 Introduction
			3.1.1	 Endometriotic Concerns
			3.1.2	 Theoretical Concerns
			3.1.3	 Müllerian Cells of Origin
			3.1.4	 Non-Müllerian Cells of Origin
			3.1.5	 Activation, Transition, and Inactivation
		3.2	 Cells of Origin
			3.2.1	 Ovarian Germinal Epithelium
			3.2.2	 Extension of Tubal Epithelium
			3.2.3	 Müllerian Rests
			3.2.4	 Endometriosis as a Cell of Origin
			3.2.5	 Wolffian (Mesonephric) Duct Remnants
			3.2.6	 Coelomic Metaplasia
			3.2.7	 Endometrium (Acquired Müllerian Disease)
			3.2.8	 Bone Marrow Stem Cells
		3.3	 Methods of Dissemination
			3.3.1	 Retrograde Menstruation
			3.3.2	 Retrograde Menstruation Model
			3.3.3	 Hematogenous/Venous Dissemination
			3.3.4	 Lymphatic Dissemination
			3.3.5	 Surgical Transplantation
			3.3.6	 Embryonic Development
			3.3.7	 Direct Extension
		3.4	 Conclusion
		References
	4: Pathogenesis of Endometriosis: Role of Platelets in Endometriosis
		4.1	 Introduction
		4.2	 A Primer on Platelets
		4.3	 Role of Platelets in Endometriosis Progression
			4.3.1	 Platelet Activation by Thrombin/Thromboxane
			4.3.2	 Platelets-Mediated Suppression of Cytotoxicity in NK Cells in Endometriosis
			4.3.3	 Platelets Promote Progression of Endometriotic Lesions
			4.3.4	 Platelets, Estrogen Production, and Ovarian Steroid Receptor
			4.3.5	 Endometriosis and Hypercoagulability
			4.3.6	 Therapeutic Implications
		4.4	 Summary and Perspective
		References
	5: Pathogenesis of Endometriosis: Role of Macrophages in Endometriosis
		5.1	 Introduction
		5.2	 Fundamentals of Macrophages
		5.3	 Macrophages and Innate Immune Cells
			5.3.1	 Role of Macrophages/NK Cells in Endometriosis
			5.3.2	 Macrophages and Fibrogenesis in Endometriosis
		5.4	 Macrophages in Early and Advanced Endometriosis
			5.4.1	 Mφ Infiltration in Eutopic and Ectopic Endometrium
			5.4.2	 Mφ Infiltration Based on Phases of Menstrual Cycle
			5.4.3	 Mφ Infiltration Based on Morphologic Appearance of Lesions
			5.4.4	 Correlation Between Mφ Infiltration and HGF Expression/MVD
		5.5	 Regulation of HGF by Basal and Stimulated Mφ
		5.6	 ER/PR Expression in Mφ and Role of Ovarian Steroids
		5.7	 Crosstalk Between Inflammation and Ovarian Steroids
		5.8	 Effect of GnRHa on Tissue Inflammation
		5.9	 Summary and Perspective
		References
	6: Pathogenesis of Endometriosis: Genetics
		6.1	 Introduction
		6.2	 Discovery of Endometriosis Genetic Susceptibility Variants
		6.3	 Genome-Wide Association Studies
		6.4	 Conclusions and Future Work
		References
	7: Pathogenesis of Endometriosis: Progesterone Resistance in Women with Endometriosis
		7.1	 Introduction
		7.2	 Mechanisms of Progesterone Resistance in Endometriosis
			7.2.1	 Altered Steroid Receptor Levels in Endometriosis
		7.3	 Clinical Relevance of Progesterone Resistance
			7.3.1	 Prediction of Resistance to Progestin Therapy
			7.3.2	 Treatment Options in Patients with Progesterone Resistance
		References
	8: Classification and Clinical Staging of Endometriosis
		8.1	 Introduction
		8.2	 The rASRM Score
		8.3	 The EFI (Endometriosis Fertility Index)
		8.4	 The Enzian Classification
			8.4.1	 The #Enzian Classification
			8.4.2	 Coding of the #Enzian Classification
		8.5	 Conclusion
		References
	9: Endometriosis Diagnostic Modalities: The Sonographic Diagnosis of Deep Endometriosis
		9.1	 Introduction
		9.2	 Uterus Assessment
		9.3	 Adnexal Assessment
		9.4	 Ovarian Position Assessment (Soft Markers)
		9.5	 Pouch of Douglas Assessment
		9.6	 Deep Endometriosis Assessment
		9.7	 Tenderness-Guided Transvaginal Ultrasonography
		9.8	 Gel Sonovaginography
		9.9	 Rectal Water-Contrast Transvaginal Ultrasonography
		9.10	 Three-Dimensional Ultrasonography
		9.11	 Comparison with Other Imaging Techniques
		9.12	 Conclusion
		References
	10: The Evil Quadruplets: Painful Conditions Coexisting with Endometriosis
		10.1	 Introduction
		10.2	 Mechanism of Coexisting Conditions
		10.3	 Bladder Pain Syndrome/Interstitial Cystitis
			10.3.1	 Pathophysiology
			10.3.2	 Epidemiology
			10.3.3	 Symptoms
			10.3.4	 Diagnosis
			10.3.5	 Treatment
				10.3.5.1	 First-Line Interventions
				10.3.5.2	 Second-Line Interventions
				10.3.5.3	 Third-Line Intervention
				10.3.5.4	 Fourth-Line Intervention
				10.3.5.5	 Fifth-Line Intervention
				10.3.5.6	 Sixth-Line Intervention
			10.3.6	 Treatments That Should Not Be Offered
		10.4	 Spastic Pelvic Floor Syndrome
			10.4.1	 Pathophysiology
			10.4.2	 Epidemiology
			10.4.3	 Diagnosis
			10.4.4	 Treatment
		10.5	 Irritable Bowel Syndrome
			10.5.1	 Epidemiology
			10.5.2	 Pathophysiology
			10.5.3	 Diagnosis
			10.5.4	 Treatment
				10.5.4.1	 Diet
				10.5.4.2	 Probiotics
				10.5.4.3	 Gluten
				10.5.4.4	 IBS-C
				10.5.4.5	 IBS-D
		10.6	 Suggestions from the Author
		References
Part II: Endometriosis: Across the Lifespan
	11: In Utero and Early-Life
		11.1	 Brief Historical Background
		11.2	 The Possible Fetal Origin of Ectopic Endometrium
			11.2.1	 Endometrial Glands Development
		11.3	 Development of Ectopic Endometrial Foci During Fetal Life
		11.4	 Perimenarcheal Endometriosis
		References
	12: Endometriosis in Adolescence
		12.1	 Prevalence and Epidemiology
		12.2	 Risk Factors
		12.3	 Pathophysiology
		12.4	 Clinical Presentation
		12.5	 Evaluation
		12.6	 Laboratory/Imaging Studies
		12.7	 Trial of Medical Therapy
		12.8	 Diagnostic Surgery
		12.9	 Surgical Treatment
		12.10	 Postoperative Medical Therapies
		12.11	 Combined Hormonal Contraception
		12.12	 Progestin-Only Therapies
		12.13	 Androgens
		12.14	 Gonadotropin-Releasing Hormone Agonists and Antagonists
		12.15	 Complementary Therapies
		12.16	 Support and Long-Term Follow-Up
		References
	13: Endometriosis in Reproductive Years: Fertility
		13.1	 Effect of Endometriosis on Fertility
		13.2	 Effect of Surgery on Infertility
		13.3	 Peritoneal Endometriosis
		13.4	 Deep Infiltrating Endometriosis
		13.5	 Ovarian Endometriosis
		13.6	 Endometriosis Fertility Index
		References
	14: Endometriosis in Reproductive Years: ART and Endometriosis
		14.1	 Introduction
		14.2	 Epidemiology
		14.3	 Diagnosis Delay
		14.4	 Pathogenesis and Pathophysiology
		14.5	 Risk Factors
		14.6	 Relationship Between Endometriosis and Infertility
		14.7	 Diagnosis of Endometriosis
		14.8	 Biomarkers
		14.9	 Classification of Endometriosis
		14.10	 Differential Diagnosis of Endometriosis
		14.11	 Treatment of Infertility Associated with Endometriosis
			14.11.1 Medical Treatment
			14.11.2 Surgical Treatment
			14.11.3 Combined Medical and Surgical Treatment
			14.11.4 Intrauterine Insemination (IUI)
			14.11.5 In Vitro Fertilization (IVF)
		14.12	 Conclusions
		References
	15: Endometriosis in Reproductive Years: The Origin of Pain in Endometriosis and Adenomyosis
		15.1	 Pathogenesis of Endometriotic Lesions
		15.2	 Pathophysiologic Origin of Pain
			15.2.1	 Endometriosis-Associated Pain
		15.3	 Principles of Pain Development
			15.3.1	 Pathogenesis of Specific Forms of Pain
			15.3.2	 Neurogenic Inflammation
			15.3.3	 Development of Central Sensitization with Spinal Hyperalgesia
		References
	16: Endometriosis in Reproductive Years: Surgical Management of Colorectal Endometriosis
		16.1	 Introduction
		16.2	 Rectal Shaving
		16.3	 Disc Excision/The Rouen Technique
		16.4	 Segmental Bowel Resection for DE
		References
	17: Endometriosis in  Peri- and Postmenopausal Year
		17.1	 Introduction
		17.2	 Prevalence
		17.3	 Pathophysiology
		17.4	 Diagnosis and Clinical Manifestations
		17.5	 Treatment
			17.5.1	 Management of Fertility Problems in Women with Endometriosis After the Age of 40
			17.5.2	 Management of Pain Problems in Women with Endometriosis After the Age of 40
			17.5.3	 Hormone Replacement Therapy and Management of Menopausal Symptoms in Women with Endometriosis After the Age of 40
			17.5.4	 Asymptomatic Patient in Women with Endometriosis After the Age of 40
		17.6	 Risk of Malignant Transformation
		17.7	 Conclusion
		References
	18: Pregnancy and Obstetric Outcomes in Endometriosis
		18.1	 Introduction
		18.2	 Pregnancy
		18.3	 Obstetrics
		References
Part III: Endometriosis: Miscellaneous Clinical Presentations and Management
	19: Recurrent Endometriosis
		19.1	 Definition
		19.2	 Mechanisms of Recurrence
		19.3	 Timing of Recurrence
		19.4	 Risk Factors for Recurrent Endometriosis
		19.5	 Prevention of Recurrence
		19.6	 Management of Recurrent Endometriosis
			19.6.1	 Early Recurrence
			19.6.2	 Medium-/Long-Term Recurrence
		19.7	 Conclusion
		References
	20: Extrapelvic Endometriosis
		20.1	 Introduction
		20.2	 Abdominal Wall Endometriosis: Scar, Perineal, Umbilical, and Inguinal Endometriosis
		20.3	 Visceral Endometriosis
		20.4	 Thoracic Endometriosis Syndrome
		20.5	 Other Sites
		References
	21: Pelvic Nerve Endometriosis (Neuropelveology)
		21.1	 Introduction
		21.2	 Etiology and Pathophysiology
		21.3	 Basic Pelvic Neuroanatomy
		21.4	 Clinical Evaluation
			21.4.1	 Non-discogenic Sciatica
			21.4.2	 Sacral Plexus Endometriosis
			21.4.3	 Sciatic Nerve (SN) Endometriosis
			21.4.4	 Femoral Nerve Endometriosis
			21.4.5	 Obturator Nerve Endometriosis
		21.5	 Diagnosis of Nerve Endometriosis (Neuropelveologic Diagnosis)
			21.5.1	 Electromyography
			21.5.2	 Urodynamic Test
		21.6	 Imaging of the Pelvic Nerves
			21.6.1	 Ultrasonography
			21.6.2	 Magnetic Resonance Imaging
		21.7	 Exclusion of Other Reasons of Sciatica
		21.8	 Natural Course of Nerve Endometriosis
		21.9	 Treatment of Nerve Endometriosis
			21.9.1	 Medical Treatment
			21.9.2	 Surgical Treatment
		21.10	 Long-Term Prognosis After Nerve Resection
		References
	22: Fertility Preservation in Endometriosis
		22.1	 Introduction
		22.2	 Population Characteristics
			22.2.1	 Endometriosis and Poor Oocyte Quality
			22.2.2	 Endometriosis and Reduction of Ovarian Reserve
		22.3	 Clinical Impact of Surgical Removal of Endometriomas
		22.4	 Strategies for COS in Patients with Endometriosis
		22.5	 Fertility Preservation by Cryopreservation of Ovarian Tissue
		22.6	 Conclusion
		References
	23: Malignancy Risks Associated with Endometriosis: Epidemiology
		23.1	 Introduction
		23.2	 Epidemiological Evidence on the Associations Between Endometriosis and Malignancy
			23.2.1	 Gynaecological Cancers
				23.2.1.1	 Ovarian Cancer
				23.2.1.2	 Breast Cancer
				23.2.1.3	 Endometrial Cancer
			23.2.2	 Other Types of Cancer
				23.2.2.1	 Skin Cancer
				23.2.2.2	 Thyroid Cancer
				23.2.2.3	 Colorectal Cancer
				23.2.2.4	 Cervical Cancer
				23.2.2.5	 Other Cancers
		23.3	 Research Methodology Considerations
			23.3.1	 Temporality
			23.3.2	 Misclassification and Population Sampling
			23.3.3	 Confounding and Mediation
			23.3.4	 Study Robustness and Study Heterogeneity
			23.3.5	 Endometriosis and Cancer Disease Heterogeneity
			23.3.6	 Publication Bias
		23.4	 Potential Pathophysiological Mechanisms Underlying the Associations Between Endometriosis and Cancer
		23.5	 How Should Clinicians Inform Women with Endometriosis Regarding Their Cancer Risk?
		23.6	 Cancer Screening and Monitoring Recommendations
		23.7	 Conclusion
		References
	24: Malignancy Risks Associated with Endometriosis: Clinical Aspects
		24.1	 Introduction
		24.2	 Background
		24.3	 Clinic
			24.3.1	 Risk Factors
			24.3.2	 Diagnosis
			24.3.3	 Clinical Presentation
			24.3.4	 Therapy
			24.3.5	 Clinical Implications
		References
	25: Psychological Considerations in Endometriosis
		25.1	 Introduction
		25.2	 Endometriosis and Quality of Life
		25.3	 Psychological and Emotional Impact of Endometriosis
		25.4	 Endometriosis and Sexuality
		25.5	 Endometriosis Treatments and Quality of Life Assessment
		25.6	 Effects of Endometriosis Treatments on Sexual Function
		References
	26: Nutritional Interventions, Complementary and Alternative Medicine for Endometriosis
		26.1	 Introduction
		26.2	 Nutritional Interventions
			26.2.1	 Vitamin D and Fatty Acids
			26.2.2	 Antioxidant Diet
			26.2.3	 Combination of Nutrients
			26.2.4	 What About Nutrients to Avoid?
		26.3	 Complementary and Alternative Medicine
			26.3.1	 Chinese Medicine Decoctions
			26.3.2	 Herbal Medicines (Phytotherapy)
			26.3.3	 Herbal Extracts Therapies
			26.3.4	 Acupuncture and Electrotherapy
			26.3.5	 Osteopathic Manipulative Therapy and Yoga
		References
	27: Prevention of Endometriosis: Is It Possible?
		27.1	 Defining Prevention
		27.2	 Primary Prevention of Endometriosis
		27.3	 Secondary Prevention of Endometriosis
		27.4	 Tertiary Prevention of Endometriosis
		27.5	 Conclusion
		References
	28: Cost Estimates Associated with Diagnosis and Treatment of Endometriosis
		28.1	 Introduction
			28.1.1	 What Is Endometriosis?
			28.1.2	 What Is the Prevalence of Endometriosis?
			28.1.3	 What Are the Signs and Symptoms of Endometriosis?
			28.1.4	 What Are the Impacts of Endometriosis?
				28.1.4.1	 Impacts on Health-Related Quality of Life
				28.1.4.2	 Impacts on Fertility
				28.1.4.3	 Impacts on Psychosocial Functioning
				28.1.4.4	 Impacts on Employment and Work Productivity
			28.1.5	 Why Are Costs of Endometriosis Important?
		28.2	 Costs Associated with the Diagnosis of Endometriosis
			28.2.1	 How Is Endometriosis Diagnosed?
			28.2.2	 What Are the Challenges Associated with Diagnosing Endometriosis?
				28.2.2.1	 Unnecessary Investigations and Lack of Reliable, Low-Cost Diagnostics for Endometriosis
				28.2.2.2	 What Are the Impacts of a Delayed Diagnosis?
			28.2.3	 Potential Investigations to Aid the Diagnosis of Endometriosis
				28.2.3.1	 Endometriosis Biomarkers
				28.2.3.2	 Imaging
		28.3	 Costs Associated with the Treatment of Endometriosis
			28.3.1	 How Is Endometriosis Treated?
			28.3.2	 Cost of Medical Treatments for Endometriosis
			28.3.3	 Costs Associated with Surgical Interventions for Endometriosis
				28.3.3.1	 Cost Differences Between Surgical Procedures
				28.3.3.2	 Cost Differences Between Medical and Surgical Treatment of Endometriosis
				28.3.3.3	 Hospital Admissions
				28.3.3.4	 Risk of Disease Recurrence
				28.3.3.5	 Costs Associated with Treating Endometriosis-Related Infertility/Subfertility
		28.4	 Indirect Costs Associated with Endometriosis
			28.4.1	 What Are the Indirect Costs Associated with Work Absences and Productivity?
			28.4.2	 What Are the Indirect Costs Associated with Surgery?
			28.4.3	 Why Are Indirect Costs Important?
		28.5	 Conclusions
			28.5.1	 What Is the Global Economic Burden of Endometriosis?
			28.5.2	 Limitations and Future Directions
				28.5.2.1	 Lack of Control Groups
				28.5.2.2	 Inclusion of Patient Profile Characteristics
				28.5.2.3	 Costs Associated with Recurrence Risk
				28.5.2.4	 Value-Based Care Studies
				28.5.2.5	 Lack of Studies Quantifying Non-Healthcare Costs and Indirect Costs
			28.5.3	 Concluding Remarks
		References
Part IV: Adenomyosis
	29: What Is Adenomyosis?
		29.1	 Introduction
		29.2	 From Adenomyoma to Adenomyosis: The Endometrial Myometrial Interface
		29.3	 Diagnosing Adenomyosis
			29.3.1	 Clinical Diagnosis
			29.3.2	 Imaging Diagnosis
				29.3.2.1	 Magnetic Resonance Imaging
				29.3.2.2	 Ultrasound
			29.3.3	 Biomarker-Based Diagnosis
		29.4	 Mapping of Adenomyosis
		29.5	 Attempts at Creating a Classification of Adenomyosis
		29.6	 Adenomyosis in Young Women and After the Menopause
		29.7	 Variants with Similarities to Adenomyosis
		29.8	 Conclusion
		References
	30: A History of Adenomyosis
		30.1	 Introduction
		30.2	 The Work of Thomas Cullen
		30.3	 Otto Frankl and the Birth of Adenomyosis
		30.4	 Conclusion
		References
	31: Insights on Adenomyosis Development
		31.1	 Introduction
		31.2	 Risk Factors for Adenomyosis
		31.3	 Pathogenic Theories on the Origin of Adenomyosis
			31.3.1	 Invasion from the Endometrium
			31.3.2	 Metaplasia
		31.4	 Pathogenic Mechanisms
			31.4.1	 Genetics and Epigenetics
			31.4.2	 Sex Steroid Hormone Function
			31.4.3	 Pituitary Hormone Function
			31.4.4	 Inflammation
			31.4.5	 Immune Response
			31.4.6	 Proliferation and Cell Survival
			31.4.7	 Migration, Invasion, and Fibrosis
			31.4.8	 Angiogenesis
			31.4.9	 Neurogenic Factors and Neurogenesis
		31.5	 Conclusions
		References
	32: Classification and Staging of Adenomyosis
		32.1	 Introduction
		32.2	 What Is the Role of MRI and Ultrasound for an Accurate Classification?
		32.3	 Difficulties with Classification: Correlation to Histology and Symptoms
		32.4	 Conclusion
		References
	33: Noninvasive Diagnosis of Adenomyosis: Ultrasonography
		33.1	 Introduction
		33.2	 Ultrasound Features of Adenomyosis
			33.2.1	 2D TVS Features of Adenomyosis
			33.2.2	 3D TVS Features of Adenomyosis
		33.3	 Ultrasound Evaluation and Description of Adenomyosis
			33.3.1	 TVS Types of Adenomyosis
			33.3.2	 TVS Uterine Wall Location of Adenomyosis
			33.3.3	 TVS Myometrial Layer Location of Adenomyosis
			33.3.4	 TVS Size and Extension of Adenomyosis Inside the Uterus
		33.4	 Ultrasound Diagnostic Accuracy of Adenomyosis Compared to Histology
		33.5	 Ultrasound Diagnosis of Adenomyosis Compared to MRI Diagnosis
		33.6	 Ultrasound Diagnosis of Adenomyosis and Association with Endometriosis
		33.7	 Ultrasound Diagnosis of Adenomyosis and Association with Symptoms
		33.8	 Conclusions
		References
	34: Noninvasive Diagnosis of Adenomyosis: Magnetic Resonance Imaging (MRI)
		34.1	 Introduction
			34.1.1	 The Role of MRI in Adenomyosis Diagnosis
			34.1.2	 Overall Diagnostic Performance of MRI in Adenomyosis Diagnosis
		34.2	 Uterine Zonal Anatomy in MRI and Adenomyosis
		34.3	 Diagnostic Signs of Adenomyosis in MRI
			34.3.1	 Direct Signs
			34.3.2	 Indirect Signs
			34.3.3	 Alterations in the Junctional Zone
			34.3.4	 Adenomyoma
		34.4	 Technical Requirements
		References
	35: Adenomyosis in Adolescence
		35.1	 Diagnosis of Adenomyosis in Adolescents
		35.2	 Juvenile Cystic Adenomyomas
		35.3	 Surgical Treatment of Adenomyosis in Adolescents
		35.4	 Medical Treatment of Adenomyosis in Adolescents
		35.5	 Conclusion
		References
	36: Adenomyosis in Reproductive Years: Abnormal Uterine Bleeding and Pain
		36.1	 Introduction
		36.2	 Symptoms of Pain and AUB
		36.3	 Pain of Adenomyosis in Patients at Younger Reproductive Age
		36.4	 Pain and AUB of Adenomyosis in Patients at Elder Reproductive Age
		36.5	 The Efficacy of Adenomyomectomy for Symptomatic Adenomyosis
		36.6	 Conclusion
		References
	37: Adenomyosis in Reproductive Years: Fertility and ART in Adenomyosis
		37.1	 Introduction
		37.2	 Adenomyosis and Fertility Outcome
			37.2.1	 Proposed Theories for Factors Causing Infertility
			37.2.2	 Effect on Pregnancy Outcomes
		37.3	 Management
			37.3.1	 Medical Management of Adenomyosis-Related Infertility
			37.3.2	 Surgical Management of Adenomyosis-Related Infertility
		37.4	 Conclusion
		References
	38: Pregnancy and Obstetric Outcomes in Adenomyosis
		38.1	 Introduction
			38.1.1	 Fertility Outcomes after ART
			38.1.2	 Pregnancy Outcomes
			38.1.3	 Obstetrical Outcomes
			38.1.4	 Neonatal Outcomes
		38.2	 Conclusion
		References
	39: Does Adenomyosis Increase Cancer Risk?
		39.1	 Introduction
		39.2	 Malignant Transformation of Adenomyosis
		39.3	 Diagnosis and Staging of Endometrial Cancer in Patients with Adenomyosis
		39.4	 Conclusion
		References
Part V: Clinical Pharmaceutical Features of Drugs Used in Endometriosis and Adenomyosis Treatment and Guidelines
	40: Hormonal Therapy in Endometriosis and Adenomyosis: Oral Contraceptives
		40.1	 Treatment of Endometriosis
		40.2	 Treatment of Adenomyosis
		40.3	 Mechanism of LEP
		40.4	 Endometriosis in Adolescents
		References
	41: Hormonal Therapy in Endometriosis and Adenomyosis: Progestins
		41.1	 Introduction
		41.2	 Progestins in the Treatment of Endometriosis
			41.2.1	 Classification
			41.2.2	 Mechanism of Action
			41.2.3	 Molecular Effects on Target Tissue
			41.2.4	 Route of Administration
				41.2.4.1	 Oral Route
					41.2.4.1.1 Dienogest
					41.2.4.1.2 Norethisterone (Norethindrone) Acetate
					41.2.4.1.3 Dydrogesterone
					41.2.4.1.4 Medroxyprogesterone Acetate
					41.2.4.1.5 Cyproterone Acetate
				41.2.4.2	 Other Routes of Application
					41.2.4.2.1 Depot Injections
					41.2.4.2.2 Subdermal Implants
					41.2.4.2.3 Intrauterine Systems
			41.2.5	 Side Effects
		41.3	 Results for Treatment for Pain
		41.4	 Patients with Rectovaginal Endometriosis
		41.5	 Patients with Infertility
		41.6	 Postoperative Hormonal Suppression
		41.7	 Progestins in Adenomyosis
		41.8	 Recent Guidelines on Hormonal Therapy with Progestins in Endometriosis
		41.9	 Conclusion
		References
	42: Hormonal Therapy in Endometriosis and Adenomyosis: Danazol, Aromatase Inhibitors
		42.1	 Introduction
		42.2	 Endometriosis
			42.2.1	 Danazol
			42.2.2	 Aromatase Inhibitors
		42.3	 Adenomyosis
			42.3.1	 Danazol
			42.3.2	 Aromatase Inhibitors
		42.4	 Conclusion
		References
	43: GnRH Agonists and Antagonists in Endometriosis and Adenomyosis Therapy
		43.1	 GnRH Physiology
		43.2	 Clinical Uses
		43.3	 Impact of GnRH Agonist Amino Acid Substitution on Clinical Effect
		43.4	 Adenomyosis
		43.5	 Endometriosis
		43.6	 GnRH Agonists for the Treatment of Endometriosis
		43.7	 Impact on GnRH Agonists on Bone
		43.8	 Add-Back Therapy as a Strategy to Protect Bone and Extend GnRH Agonist Use
		43.9	 Estrogen Threshold Hypothesis and the Suggestion of an Alternative Strategy
		43.10	 Empiric Use of GnRH Agonists
		43.11	 Post-Operative Use of GnRH Agonists
		43.12	 GnRH Antagonists for the Treatment of Endometriosis
		43.13	 Conclusion
		References
	44: Recent Guidelines on Endometriosis and Adenomyosis
		44.1	 Introduction
		44.2	 Methodology
		44.3	 Diagnosis of Endometriosis
		44.4	 Medical Treatment for Endometriosis-Associated Pain
		44.5	 Surgical Treatment for Endometriosis-Associated Pain
		44.6	 Management of Endometriosis-Associated Infertility
		44.7	 Adenomyosis
		44.8	 Conclusion
		References
Index