Hormonal Pathology of the Uterus (Advances in Experimental Medicine and Biology Book 1242)

Hormonal influences, both natural and iatrogenic, are implicated in the most frequent health issues of women. Endometrial cancer is now the most common gynecologic cancer in the United States and the industrialized world. This cancer is strongly related to hormonal and metabolic factors. In addition, breast cancer treated with hormone therapy (Tamoxifen) may, in some cases, be associated with uterine pathology. Hormone therapy is used to improve the physiological effects and counteract abnormal and deleterious effects of “natural” hormonal activity. Millions of women receive hormone therapy at some point of their life: using oral contraceptives, reproductive technology, treatment for post-menopausal symptoms, among other uses. This book addresses a range of women’s health issues, from fertility to neoplasms, and their relationship with natural and iatrogenic hormonal effects. Chapters include clinical and pathological descriptions, theoretical and practical medical issues, and original studies and cases. Controversial issues in certain hormone therapies are presented with updated concepts based on clinical studies and novel statistical methods. The book will be useful for specialized and general physicians, oncologists, endocrinologists, researchers, medical students, and others in the field of women’s health. Contents 6 Contributors 7 Hormonal Biophysiology of the Uterus 9 1 Uterine Development 9 2 Endometrial Cyclic Changes 10 3 Uterus at Menopause 15 References 20 Hormonal Effects in Reproductive Technology with Focus on Diminished Ovarian Reserve 21 1 Introduction 21 2 Causes of Infertility 22 2.1 Male Factor 22 2.2 Tubal Factor 22 2.3 Ovarian Reserve 22 2.3.1 Antral Follicle Count (AFC) 23 2.3.2 Basal Follicle-Stimulating Hormone (b-FSH) 24 2.3.3 Anti-Mullerian Hormone (AMH) 25 3 Ovulation Induction 25 4 Maintenance of the Antral Follicle Pool 26 4.1 Factors Promoting Growth of Pre-antral and Antral Follicles 27 4.1.1 Androgens 27 4.1.2 Growth Hormone 28 4.1.3 Platelet-Rich Plasma 29 4.1.4 Estrogen Priming 30 5 Optimizing Oocyte Production 31 5.1 Individualized Egg Retrieval 31 5.2 In Vitro Maturation of Immature Oocytes (IVM) 31 5.3 Rebound 32 6 Embryo Factors 33 6.1 Fertilization and Implantation 33 6.1.1 Fertilization 34 6.1.2 Ectopic Pregnancy 34 6.2 Embryo Selection 34 6.2.1 Embryo Morphology 35 6.2.2 Preimplantation Genetic Testing 36 References 37 Role of Hormones in Common Benign Uterine Lesions: Endometrial Polyps, Leiomyomas, and Adenomyosis 45 1 Introduction 45 2 Leiomyoma 46 2.1 Definition, Epidemiology, Clinical Features 46 2.2 Risk Factors and Etiopathogenesis 48 2.3 Treatment 49 2.3.1 Medical Treatment 50 2.3.2 Interventional Procedures for ULs 51 2.3.3 Surgical Treatment 51 3 Adenomyosis 52 3.1 Definition, Epidemiology, Clinical Features 52 3.2 Risk Factors, Etiopathogenesis 53 3.3 Treatment 54 3.3.1 Steroidal Treatments 54 3.3.2 Nonsteroidal Medical Treatments 55 3.3.3 Interventional Procedures 55 3.3.4 Surgical Treatment 56 4 Endometrial Polyps 56 4.1 Definition, Epidemiology, Clinical Features 56 4.2 Etiopathogenesis 56 4.3 Treatment 57 5 Conclusions 58 References 59 Endometrial Carcinoma and its Precursors 67 1 Introduction 67 2 Endometrial Hyperplasia 69 2.1 Endometrial Intraepithelial Neoplasia Classification 70 2.2 Clinical Presentation and Diagnostic Evaluation 70 2.3 Management 70 3 Endometrial Carcinoma 72 3.1 Staging, Prognosis with Risk Factors 74 3.2 Diagnosis 76 3.3 Hormone Receptors 76 3.3.1 Estrogen 76 3.3.2 Progesterone 77 3.4 Management 77 3.4.1 Surgical Approaches 77 3.4.2 Chemotherapy and Hormone Therapy 78 3.4.3 Radiotherapy 78 References 78 Endometriosis and Endometriosis-Associated Ovarian Cancer (EAOC) 81 1 Introduction 81 2 Pathogenesis 82 3 The Relationship of Endometriosis and Ovarian Cancer 82 4 Epigenetics 87 5 The Role of Microenvironment and Immune System 87 6 Synchronous Endometrial Carcinoma with Endometrioid Ovarian Carcinoma 89 7 Treatment for EAOC 90 8 Conclusion 91 References 91 Hormone Therapy in Menopause 96 1 Introduction 96 2 Contraindications for MHT 97 3 Historical Overview 97 4 Before the WHI 97 4.1 Observational Data 97 4.2 The Postmenopausal Estrogen/Progestin Intervention (PEPI) Trial 98 4.3 The Heart and Estrogen Replacement Study (HERS) 98 5 The Women’s Health Initiative (WHI) Study 99 5.1 Intention and Design 99 5.2 Aftermath and Clinical Consequences of the WHI “Early News” 100 5.3 WHI Late News but Good News 101 6 The Timing Hypothesis 101 6.1 Vasomotor Symptoms 105 6.2 Physiology of VMS 106 7 Treatment of VMS 107 7.1 Estrogen Therapy 107 7.2 Nonhormonal Pharmacologic (Prescription) Therapies 108 7.2.1 Paroxetine 108 7.3 Contraindications Women on Tamoxifen 108 7.4 Gabapentin (GABA) 108 7.5 Clonidine 109 8 Genitourinary Syndrome of Menopause 109 9 Treatment Options 110 10 Off-Label Options 111 10.1 Vaginal Testosterone 111 10.2 Vaginal Laser 112 11 Osteoporosis Prevention 114 12 Primary Ovarian Insufficiency and Early Menopause 115 13 Vasomotor Symptoms and Cardiovascular Disease Risk 117 14 Other Benefits of MHT 118 14.1 Joints and Muscles 118 14.2 Metabolism 119 14.3 Colorectal Cancer 119 15 Risks 119 15.1 Venous Thromboembolism (VTE), Gallbladder Disease, Stroke 119 15.2 Breast Cancer 120 15.3 MHT for Primary Prevention of CVD and Other Chronic Diseases 121 16 Summary and Conclusions 121 References 122 Replacement Hormone Therapy for Gender Dysphoria and Congenital Sexual Anomalies 128 1 Definitions 129 2 Therapeutic Approach 130 3 Hormonal Therapy: Introduction 130 4 Hormonal Therapy for the Transgender Female 132 5 Hormonal Therapy for the Transgender Male 134 5.1 Effects of Hormonal Therapy for the Transgender Male: Histological Aspects 135 6 Cancer Screening After Hormonal Treatment in Transgender Persons 136 7 Congenital Sexual Anomalies 139 7.1 Hormonal Treatment: General Considerations 140 7.2 Patients with 45, X0/46, XY and 46, XX/46, XY Mosaicism 141 7.3 Turner Syndrome and Variants: (45,X-) and 45, X0/46,XX Mosaicism 142 7.4 Klinefelter Syndrome 144 7.5 Androgen Insensitivity Syndrome 144 7.6 Müllerian Agenesis 145 8 Conclusions 147 References 148 Hormone Therapy Effects on the Uterus 151 1 General Considerations 151 2 Iatrogenic Hormonal Effects on the Uterus 153 2.1 Hormonal Contraceptive Therapy 153 2.2 Hormonal Therapy for Infertility 157 2.3 Effects of Hormone Therapy on Benign Uterine Lesions 161 2.3.1 Leiomyomas 161 2.3.2 Adenomyosis 163 2.3.3 Endometrial Polyps 164 3 Hormone Replacement Therapy Effects on Uterus 164 3.1 Effects of ERT 165 3.2 Effects of Combined HRT 168 4 Effects of Antineoplastic Hormone Therapy 174 4.1 Progesterone Therapy 174 4.2 Tamoxifen Therapy for Breast Cancer 178 5 Conclusions 181 References 182 Index 184 Front Matter ....Pages i-viii Hormonal Biophysiology of the Uterus (Liane Deligdisch-Schor, Angelica Mareş Miceli)....Pages 1-12 Hormonal Effects in Reproductive Technology with Focus on Diminished Ovarian Reserve (David Barad)....Pages 13-36 Role of Hormones in Common Benign Uterine Lesions: Endometrial Polyps, Leiomyomas, and Adenomyosis (Myriam Kossaï, Frédérique Penault-Llorca)....Pages 37-58 Endometrial Carcinoma and its Precursors (Pouya Javadian, Farr Nezhat)....Pages 59-72 Endometriosis and Endometriosis-Associated Ovarian Cancer (EAOC) (Tanja Pejovic, Sarah Thisted, Michael White, Farr R. Nezhat)....Pages 73-87 Hormone Therapy in Menopause (John Paciuc)....Pages 89-120 Replacement Hormone Therapy for Gender Dysphoria and Congenital Sexual Anomalies (Angelica Mareş Miceli)....Pages 121-143 Hormone Therapy Effects on the Uterus (Liane Deligdisch-Schor)....Pages 145-177 Back Matter ....Pages 179-185