Andrology: Male Reproductive Health and Dysfunction

Preface
Contents
Editors and Contributors
About the Editors
Contributors
1: Scope and Goals of Andrology
	1.1	 Definition and Status of Andrology
	1.2	 Andrology, Gynecology, Reproductive Medicine: Reproductive Health
	1.3	 Infertility, Subfertility, Sterility, Fecundity: Definition of Terms
	1.4	 The Infertile Couple as Target Patients
	1.5	 Prevalence of Infertility
	1.6	 Evidence-Based Andrology = Rational Andrology
	1.7	 The Crisis in Andrological Research
	1.8	 The Special Case of Male Contraception
	References
Part I: Physiologic Basis
	2: Physiology of Testicular Function
		2.1	 Introduction
			2.1.1	 Functional Organization of the Testes
				2.1.1.1	 Interstitial Compartment
					2.1.1.1.1 Leydig Cells
					2.1.1.1.2 Macrophages, Lymphocytes, and Nerve Fibers
				2.1.1.2	 Tubular Compartment
					2.1.1.2.1 Peritubular Cells
					2.1.1.2.2 Sertoli Cells
					2.1.1.2.3 Germ Cells
					2.1.1.2.4 Kinetics of Spermatogenesis
					2.1.1.2.5 Apoptosis and Spermatogenesis
			2.1.2	 Hormonal Control of Testicular Functions
				2.1.2.1	 Functional Organization of the Hypothalamic-Pituitary System
				2.1.2.2	 The Kisspeptin-GPR54 System
				2.1.2.3	 Gonadotropin-Releasing Hormone
					2.1.2.3.1 Structure of the GnRH
					2.1.2.3.2 Secretion of GnRH
					2.1.2.3.3 Mechanism of GnRH Action
				2.1.2.4	 Gonadotropins
					2.1.2.4.1 Structure of Gonadotropins
					2.1.2.4.2 Gonadotropin Secretion
					2.1.2.4.3 Mechanism of Gonadotropin Action
				2.1.2.5	 Endocrine Feedback Mechanism and Relative Importance of LH and FSH for Spermatogenesis
				2.1.2.6	 Local Regulation of Testicular Function
					2.1.2.6.1 Steroid Hormones
					2.1.2.6.2 Insulin-Like Factor 3
					2.1.2.6.3 Growth Factors
					2.1.2.6.4 Factors of the Immune System
			2.1.3	 Testicular Descent
			2.1.4	 Vascularization, Temperature Regulation, and Spermatogenesis
			2.1.5	 Testicular Androgens
				2.1.5.1	 Biosynthesis of Androgens
				2.1.5.2	 Transport of Testosterone in Blood
				2.1.5.3	 Extratesticular Metabolism of Testosterone
				2.1.5.4	 Mechanism of Androgen Action
				2.1.5.5	 Biological Effects of Androgens
				2.1.5.6	 Androgen Secretion and Sexual Differentiation
		References
	3: Physiology of Sperm Maturation and Fertilization
		3.1	 Introduction
		3.2	 Maturation of Spermatozoa in the Epididymis
			3.2.1	 Anatomy of the Epididymis and Sperm Transport
			3.2.2	 Epidydimal Secretion and Absorption
			3.2.3	 Sperm Maturation in the Epididymis
				3.2.3.1	 Findings from Surgical Anastomoses
				3.2.3.2	 Findings from Assisted Reproduction
			3.2.4	 Sperm Morphology and Motility
				3.2.4.1	 Changes in Sperm Morphology
				3.2.4.2	 Development of Sperm Motility
				3.2.4.3	 Regulation of Sperm Motility
				3.2.4.4	 Effects of Increased Activity of Mature Spermatozoa
			3.2.5	 Interaction with the Egg
				3.2.5.1	 Requirements for Sperm-zona Pellucida Binding
				3.2.5.2	 Development of the Acrosome Reaction
				3.2.5.3	 Sperm Chromatin Condensation and Pronucleus Formation
				3.2.5.4	 Contribution of Sperm to the Development of a Healthy Embryo
			3.2.6	 Sperm Storage in the Epididymis
				3.2.6.1	 Storage Capacity
				3.2.6.2	 Resting Stage and Protection of Spermatozoa
				3.2.6.3	 Mechanisms Preventing an Autoimmune Reaction Against Spermatozoa
		3.3	 Natural Fertilization
			3.3.1	 Erection and Ejaculation
			3.3.2	 The Ejaculate
			3.3.3	 Sperm Motility
				3.3.3.1	 Structure of the Axoneme and Flagellar Movement
				3.3.3.2	 Energy Source for Flagellar Movement
			3.3.4	 Movement of Sperm Through the Female Genital Tract
				3.3.4.1	 Movement of Uncapacitated Spermatozoa Through the Cervical Mucus
				3.3.4.2	 Capacitation and Ascent of Spermatozoa to the Oviduct
					3.3.4.2.1 Mechanism of Capacitation
					3.3.4.2.2 Hyperactivation and Migration to the Site of Fertilization
			3.3.5	 Sperm Penetration Through the Egg Envelopes
				3.3.5.1	 Penetration of the Cumulus Oophorus
				3.3.5.2	 Sperm Interaction with the Zona Pellucida
				3.3.5.3	 The Acrosome Reaction
			3.3.6	 Fusion of the Sperm with the Oolemma and Activation of the Egg
				3.3.6.1	 Membrane Fusion
				3.3.6.2	 Egg Activation
			3.3.7	 Processes After Fusion
				3.3.7.1	 Polyspermy Blockade
				3.3.7.2	 Formation of the Male Pronucleus
				3.3.7.3	 Early Embryonic Development
				3.3.7.4	 Implantation of the Embryo
		References
Part II: Classification and Diagnosis of Andrological Disorders
	4: Classification of Andrological Disorders
		4.1	 Classification by Localization and Causality
		4.2	 Classification According to Therapeutic Options
		References
	5: Anamnesis and Physical Examination
		5.1	 Anamnesis
		5.2	 Physical Examination
			5.2.1	 Body Proportions, Skeletal Structure, Fat Distribution
			5.2.2	 Voice
			5.2.3	 Skin and Hair
			5.2.4	 Olfactory Sense
			5.2.5	 Mammary Gland
			5.2.6	 Testes
			5.2.7	 Epididymis
			5.2.8	 Pampiniform Plexus
			5.2.9	 Deferent Ducts
			5.2.10	 Penis
			5.2.11	 Prostate and Seminal Vesicles
		References
	6: Ultrasound Imaging in Andrology
		6.1	 Introduction
		6.2	 Scrotal US
			6.2.1	 Indications
			6.2.2	 Methodological Standards
				6.2.2.1	 Scrotal Color Doppler Ultrasonography
				6.2.2.2	 Contrasted-Enhanced US
				6.2.2.3	 Sonoelastography
			6.2.3	 US Anatomy, Normal and Abnormal Patterns, Clinical Utility, and US Standards
				6.2.3.1	 Testis
					6.2.3.1.1 US Anatomy
					6.2.3.1.2 US Normal and Abnormal Patterns
						Testicular Volume
					6.2.3.1.3 Testicular Homogeneity and Echogenicity
					6.2.3.1.4 Testicular Vascularization
					6.2.3.1.5 Orchitis
					6.2.3.1.6 Testicular Microlithiasis
					6.2.3.1.7 Testicular Lesions
					6.2.3.1.8 Cryptorchidism
				6.2.3.2	 Epididymis and Vas Deferens
					6.2.3.2.1 US Anatomy
					6.2.3.2.2 US Abnormal Patterns
					6.2.3.2.3 Acute and Chronic Epididymitis
					6.2.3.2.4 Epididymal Nodules/Cysts
					6.2.3.2.5 Epididymal and Deferential Dilation
					6.2.3.2.6 Congenital Uni- or Bilateral Absence of Vas Deferens
				6.2.3.3	 Pampiniform Plexus and Varicocele
					6.2.3.3.1 US Anatomy
					6.2.3.3.2 US Abnormal Patterns: Varicocele
		6.3	 Prostate and Seminal Vesicles US
			6.3.1	 Indications
			6.3.2	 Methodological Standards
			6.3.3	 Anatomy, Normal and Abnormal Patterns, Clinical Utility, and Standards
				6.3.3.1	 Prostate
					6.3.3.1.1 US Anatomy
					6.3.3.1.2 US Normal and Abnormal Patterns
						Prostate Volume
						Prostate Inflammation
					6.3.3.1.3 Ejaculatory Duct (ED) Obstruction/Abnormalities
					6.3.3.1.4 Prostate Cancer
				6.3.3.2	 Seminal Vesicles and Deferential Ampullas
					6.3.3.2.1 US Anatomy
					6.3.3.2.2 US Normal and Abnormal Patterns
						Volume
					6.3.3.2.3 Echopattern Abnormalities
					6.3.3.2.4 Obstruction-Related Findings
					6.3.3.2.5 SV Agenesis, Hypoplasia, and Cysts
		6.4	 Specific Applications of Scrotal and Transrectal US
			6.4.1	 Sensitivity and Specificity in Discriminating Obstructive and Nonobstructive Azoospermia
			6.4.2	 Testis US and Surgical Sperm Retrieval in Azoospermic Subjects
			6.4.3	 Scrotal and Transrectal US and Hormonal Treatments
		6.5	 Penile US
			6.5.1	 Penile US: Indications
			6.5.2	 Penile US: Methodological Standards
			6.5.3	 Penile US: Anatomy, Normal and Abnormal Patterns, Clinical Utility, and US Standards
				6.5.3.1	 US Anatomy and Normal Patterns
				6.5.3.2	 US Abnormal Patterns
					6.5.3.2.1 Erectile Dysfunction (ED)
					6.5.3.2.2 Peyronie’s Disease
					6.5.3.2.3 Penile Mondor’s Disease (Superficial Dorsal Vein Thrombophlebitis)
					6.5.3.2.4 Priapism
					6.5.3.2.5 Penile Trauma
					6.5.3.2.6 Penile Tumors
		6.6	 Male Breast US
			6.6.1	 Male Breast US: Indications
			6.6.2	 Male Breast US: Methodological Standards
			6.6.3	 Male Breast US Anatomy, Normal and Abnormal Patterns, Clinical Utility, and US Standards
				6.6.3.1	 Male Breast US Anatomy and Normal Pattern
				6.6.3.2	 Male Breast US Abnormal Patterns
				6.6.3.3	 Gynecomastia
				6.6.3.4	 Pseudogynecomastia/Lipomastia
				6.6.3.5	 Male Breast Cancer
				6.6.3.6	 Specific Use of Male Breast US
		References
	7: Endocrine Laboratory Diagnosis
		7.1	 Gonadotropins
		7.2	 GnRH, GnRH Test, Kisspeptin
		7.3	 Prolactin
		7.4	 Testosterone, Free Testosterone, Salivary Testosterone, SHBG
		7.5	 hCG Test
		7.6	 Anti-Mullerian Hormone, Insulin-like factor 3
		7.7	 Inhibin B
		7.8	 Further Endocrine Diagnosis
		References
	8: Cytogenetic and Molecular Genetic Diagnostics
		8.1	 Introduction
		8.2	 Human Genome and Variability
		8.3	 Methods of Investigation
			8.3.1	 Conventional Cytogenetics
			8.3.2	 Fluorescence In Situ Hybridization
			8.3.3	 Array Analysis
			8.3.4	 Microdeletions of the Y Chromosome
			8.3.5	 Molecular Genetics: Sequencing
			8.3.6	 New Methods
		8.4	 Indications for Genetic Testing
		References
	9: Semen Analysis
		9.1	 Introduction
		9.2	 Semen Collection
		9.3	 Semen Analysis
			9.3.1	 Macroscopic Appearance of the Ejaculate
			9.3.2	 Initial Microscopical Examination
				9.3.2.1	 Sperm Aggregation and Agglutination
				9.3.2.2	 Non-sperm Cells
			9.3.3	 Further Microscopical Analysis
				9.3.3.1	 Sperm Motility
				9.3.3.2	 Total Sperm Numbers
				9.3.3.3	 Sperm Morphology
			9.3.4	 Additional Analyses
				9.3.4.1	 Sperm Vitality
				9.3.4.2	 Round Cells
				9.3.4.3	 Immunological Tests
		9.4	 Biochemical Analyses of Seminal Fluid
		9.5	 Microbiological Tests
		9.6	 Objective Semen Analysis
			9.6.1	 Sperm Concentration
			9.6.2	 Sperm Motility
			9.6.3	 Sperm Morphology
		9.7	 Quality Control in the Andrology Laboratory
			9.7.1	 Internal Quality Control
			9.7.2	 External Quality Control
		9.8	 Documentation, References Values, Nomenclature, and Classification of Semen Parameters
		References
	10: Sperm Quality and Sperm Function Tests
		10.1	 Introduction
			10.1.1	 Sperm Function in General
		10.2	 Sperm Survival and Viability
			10.2.1	 Sperm Survival
			10.2.2	 Sperm Vitality
		10.3	 Function of the Flagellum
			10.3.1	 Assessment of Sperm Motility by CASA
			10.3.2	 Sperm Motility After Washing
			10.3.3	 Assessment of Sperm Motility by Physiological Assays
			10.3.4	 Mobility in the Female Mucus
			10.3.5	 Antisperm Antibodies
		10.4	 Mitochondrial Function
		10.5	 The Cytoplasm
			10.5.1	 The Cytoplasmic Droplet as a Normal Structure
			10.5.2	 Excess Residual Cytoplasm
			10.5.3	 “Reactive Oxygen Species” (ROS) and Lipid Peroxidation
		10.6	 Capacitation
		10.7	 Interaction with the Fallopian Tube Epithelium
		10.8	 Interaction with the Zona Pellucida
			10.8.1	 Zona-Binding Assays
			10.8.2	 Hyaluronic Acid as Zona Surrogate
		10.9	 Acrosome Reaction
		10.10	 Sperm-ovum Fusion
			10.10.1 Hamster Ovum Penetration (HOP) Test or Sperm Penetration Assay (SPA)
		10.11	 Sperm Centrosome
		10.12	 Sperm Chromosomes
		10.13	 Sperm DNA
			10.13.1 Mitochondrial DNA (mtDNA)
			10.13.2 Nuclear DNA (nDNA)
		10.14	 DNA Fragmentation
			10.14.1 Chromatin Condensation
			10.14.2 Aniline Blue and Toluidine Blue Assay for Determination of Compaction
			10.14.3 Staining of Nucleic Acid: CMA3, Acridine Orange, and SCSA® Assays
				10.14.3.1	 CMA3 Test
				10.14.3.2	 Acridine Orange and SCSA® Assays
			10.14.4 Dispersion of DNA: Sperm Chromatin Dispersion (SCD) and Comet Assay
				10.14.4.1	 Sperm Chromatin Dispersion (SCD) Assay
				10.14.4.2	 Comet Assay
			10.14.5 “In Situ Nick Translation Assays” or TUNEL Assay
			10.14.6 Prognostic Value of DNA Tests
		10.15	 Epigenetics
		10.16	 Sperm RNA Assays
		10.17	 Translation Products
		10.18	 Conclusion and Future Developments
		References
	11: Biopsy and Histology of the Testis
		11.1	 Indication for Testicular Biopsy
		11.2	 Surgical Procedure and Tissue Preparation
			11.2.1	 Surgical Techniques
			11.2.2	 Fixation
		11.3	 Histology
			11.3.1	 Definitions
			11.3.2	 Evaluation
			11.3.3	 Score-Count Evaluation
		References
Part III: Clinics in Andrology: Secondary Hypogonadism
	12: Congenital Hypogonadotropic Hypogonadism of Hypothalamic Origin
		12.1	 Introduction
			12.1.1	 Definition of Terms
			12.1.2	 Causes of Hypothalamic Hypogonadotropic Hypogonadism
			12.1.3	 Epidemiology
		12.2	 Pathophysiology
			12.2.1	 Genetic Causes of CHH and Kallmann Syndrome
			12.2.2	 Genetic Basis of Syndromic Hypothalamic Hypogonadism
		12.3	 Clinics
			12.3.1	 Symptoms of CHH/Kallmann Syndrome in the Newborn, Infant, and Prepubertal Boy
			12.3.2	 Consequences of CHH/Kallmann Syndrome for Pubertal Development
				12.3.2.1	 Absence of Puberty
				12.3.2.2	 Arrested Puberty
				12.3.2.3	 Consequences of a Late Diagnosis of CHH/Kallmann Syndrome
		12.4	 Diagnostics
			12.4.1	 Medical History
			12.4.2	 Physical Examination and Ultrasound Imaging
			12.4.3	 Laboratory Diagnostics, Functional Testing, and Genetic Diagnostics
			12.4.4	 Magnetic Resonance Imaging (MRI) and Complementary Diagnostics
		12.5	 Treatment of CHH
		12.6	 Special Aspects: Functional Hypogonadotropic Hypogonadism
			12.6.1	 Hypogonadotropic Hypogonadism Due to Inadequate or Excessive Nutrient Intake or/and Sport Excess
			12.6.2	 Drug-Induced Hypogonadotropic Hypogonadism
		References
	13: Congenital Hypogonadotropic Hypogonadism of Pituitary Origin and Rare Syndromes with Central Hypogonadism
		13.1	 Introduction
		13.2	 Congenital Hypogonadism of Pituitary Origin
			13.2.1	 Pathophysiology
			13.2.2	 Clinic and Treatment
		13.3	 X-Linked Adrenal Hypoplasia Congenita (AHC)
			13.3.1	 Pathophysiology of AHC
			13.3.2	 Clinic and Treatment of AHC
		13.4	 Rare Syndromes with Central Hypogonadism
			13.4.1	 Prader-Willi (-Labhart) Syndrome (PWS)
				13.4.1.1	 Pathophysiology and Epidemiology of PWS
				13.4.1.2	 Clinic and Treatment of PWS
			13.4.2	 CHARGE Syndrome
			13.4.3	 Bardet-Biedl Syndrome and Laurence-Moon Syndrome
			13.4.4	 Cerebellar Ataxias with Pituitary-Induced Hypogonadism
				13.4.4.1	 Gordon-Holmes Syndrome
				13.4.4.2	 Boucher-Neuhauser Syndrome
				13.4.4.3	 Oliver-McFarlane Syndrome
		References
	14: Delayed Puberty in Boys
		14.1	 Introduction
			14.1.1	 Definition of Terms
			14.1.2	 Epidemiology
		14.2	 Physiology and Pathophysiology of Puberty
			14.2.1	 Physiology of Puberty
				14.2.1.1	 Hormonal Regulation of the Hypothalamic-Pituitary-Gonadal (HPG) Axis During Puberty
			14.2.2	 Pathophysiology of Puberty
		14.3	 Clinic
		14.4	 Diagnostics
			14.4.1	 Clinical Examination
			14.4.2	 Laboratory Investigations
			14.4.3	 Interpretation of Laboratory Findings
			14.4.4	 Diagnostic Imaging
			14.4.5	 Functional Tests
		14.5	 Treatment of Delayed Puberty
		References
	15: Pituitary Hypogonadism, Hyperprolactinemia, and Gonadotropin-Producing Tumors
		15.1	 Pituitary-Induced Hypopituitarism
			15.1.1	 Etiology and Pathogenesis
			15.1.2	 Clinic
			15.1.3	 Diagnostics
			15.1.4	 Therapy
			15.1.5	 Hypopituitarism in Hereditary Disposition
		15.2	 Isolated LH or FSH Deficiency
		15.3	 Hyperprolactinemia
			15.3.1	 Etiology and Pathogenesis
			15.3.2	 Clinic
			15.3.3	 Diagnosis
			15.3.4	 Therapy
		15.4	 Gonadotropin-Producing Tumors
		References
Part IV: Clinics in Andrology: Primary Hypogonadism (Disorders at the Testicular Level)
	16: Anorchia and Polyorchidism
		16.1	 Anorchia
			16.1.1	 Congenital Anorchia
				16.1.1.1	 Prevalence and Pathophysiology
				16.1.1.2	 Diagnostics
				16.1.1.3	 Therapy
			16.1.2	 Acquired Anorchia
				16.1.2.1	 Accidental Testicular Loss
				16.1.2.2	 Diagnostics and Therapy
				16.1.2.3	 Castration for Medical Reasons
				16.1.2.4	 Socio-cultural Castration
		16.2	 Polyorchidism
			16.2.1	 Prevalence and Pathophysiology
			16.2.2	 Diagnostics
			16.2.3	 Therapy
			16.2.4	 Historical Aspects
		References
	17: Undescended Testes
		17.1	 Epidemiology
		17.2	 Physiology and Pathophysiology of Testicular Descent
			17.2.1	 Physiology
			17.2.2	 Pathophysiology
		17.3	 Clinics
		17.4	 Diagnostics
		17.5	 Therapy
			17.5.1	 Surgical Therapy
			17.5.2	 Hormone Therapy
		17.6	 Effects of Undescended Testes on Testicular Function in Adulthood
			17.6.1	 Testicular Size
			17.6.2	 Endocrine Testicular Function
			17.6.3	 Spermatogenesis and Paternity Rates
			17.6.4	 Risk of Germ Cell Tumor
			17.6.5	 Therapeutic Options for Azoospermia
		References
	18: Varicocele
		18.1	 Epidemiology
		18.2	 Pathophysiology
		18.3	 Influence of Varicocele on Fertility
		18.4	 Clinic
		18.5	 Diagnosis
		18.6	 Influence of Varicocele Therapy on Chances of Fertility
		18.7	 Treatment Procedures
		18.8	 Varicocele in Adolescents
		References
	19: Orchitis
		19.1	 Epidemiology
		19.2	 Pathophysiology
			19.2.1	 Basic Immunobiology of the Testis
			19.2.2	 Etiopathogenesis and Classification of Testicular Inflammatory Reactions
		19.3	 Clinic and Diagnosis
			19.3.1	 Pathogen-Induced Orchitis
			19.3.2	 Non-Pathogen-Related Inflammatory Reactions in the Testis
			19.3.3	 Asymptomatic Testicular Inflammatory Reactions
		19.4	 Therapy
		References
	20: Disorders of Spermatogenesis and Spermiogenesis
		20.1	 Introduction
		20.2	 Oligoasthenoteratozoospermia
			20.2.1	 Etiopathogenesis
			20.2.2	 Clinical and Diagnostic Findings
			20.2.3	 Therapy
		20.3	 Non-obstructive Azoospermia: Disorders of Spermatogenesis
			20.3.1	 Sertoli Cell-only Phenotype
			20.3.2	 Spermatogenic Arrest
			20.3.3	 Clinic
			20.3.4	 Histopathology
			20.3.5	 Genetic Causes
			20.3.6	 Therapy
		20.4	 Specific Structural Sperm Defects: Disorders of Spermiogenesis
			20.4.1	 Macrozoospermia
			20.4.2	 Globozoospermia
			20.4.3	 Acephalic Spermatozoa
			20.4.4	 Midpiece and Flagellum Defects
			20.4.5	 Clinic and Diagnostics
			20.4.6	 Therapy
		References
	21: Klinefelter Syndrome
		21.1	 Introduction
		21.2	 Epidemiology
		21.3	 Pathophysiology
		21.4	 Clinical Picture
		21.5	 Diagnosis
			21.5.1	 General Features
			21.5.2	 Endocrine Dysfunction
			21.5.3	 Disruption of Spermatogenesis
			21.5.4	 Genetic Counselling
		21.6	 Clinical Management
		21.7	 Fertility Issues
		References
	22: XX Male and XYY Karyotype
		22.1	 XX Male
			22.1.1	 Definition and Epidemiology
			22.1.2	 Genetics
			22.1.3	 Clinic
		22.2	 XYY Karyotype
		References
	23: Structural Chromosomal Changes
		23.1	 Introduction
		23.2	 Prevalence and Consequences
		23.3	 Structural Changes of the Autosomes
		23.4	 Structural Alterations of the Sex Chromosomes
		23.5	 Y-Chromosomal AZF Microdeletions
		References
	24: Testicular Tumors
		24.1	 Incidence
		24.2	 Risk Factors
		24.3	 Malignant Germ Cell Tumors (TGCT) and Infertility
		24.4	 Germ Cell Neoplasia In Situ (GCNIS)
		24.5	 Germ Cell Tumors
			24.5.1	 Clinical Picture
			24.5.2	 Diagnostics
			24.5.3	 Primary Therapy and Planning for Further Therapy
			24.5.4	 Survival Data
			24.5.5	 Influence of Germ Cell Tumors and Therapy on Spermatogenesis
		24.6	 Endocrine Active Testicular Tumors
			24.6.1	 Leydig Cell Tumors
			24.6.2	 Sertoli Cell Tumors
		References
	25: Senescence and Late-Onset Hypogonadism
		25.1	 Physiology of Aging
		25.2	 Theories on Causes of Aging
		25.3	 Sexuality in Advanced Age
		25.4	 General Endocrine Changes in Advanced Age
		25.5	 Reproductive Functions in Advanced Age
			25.5.1	 Sex Hormones in Advanced Age
			25.5.2	 Testicular Morphology in Advanced Age
			25.5.3	 Ejaculate Parameters of Older Men
			25.5.4	 Fertility of Older Men
			25.5.5	 Reproductive Risks of Increased Paternal Age
				25.5.5.1	 Abortions and Paternal Age
				25.5.5.2	 Chromosomal Anomalies and Increased Paternal Age
				25.5.5.3	 Genetic Disorders and Increased Paternal Age
		25.6	 Late-Onset Hypogonadism
			25.6.1	 Definition
			25.6.2	 Mortality and Testosterone Deficiency
			25.6.3	 Symptoms of Late-Onset Hypogonadism
				25.6.3.1	 General Symptoms
				25.6.3.2	 Osteoporosis
				25.6.3.3	 Metabolic Syndrome
				25.6.3.4	 Psychosomatic Aspects
				25.6.3.5	 Cardiovascular Risk
			25.6.4	 Hormone Replacement in Advanced Age
				25.6.4.1	 Testosterone Substitution
				25.6.4.2	 Other Hormones
		25.7	 Diseases of the Prostate in Advanced Age
			25.7.1	 Benign Prostatic Hyperplasia (BPH)
			25.7.2	 Prostate Carcinoma
		25.8	 Outlook
		References
Part V: Clinics in Andrology: Diseases of Seminal Ducts and Accessory Sex Organs
	26: Infections and Inflammation of the Seminal Ducts and Accessory Sex Glands
		26.1	 Immunological Basics
			26.1.1	 Macrophages
			26.1.2	 Dendritic Cells
			26.1.3	 Lymphocytes
			26.1.4	 Mast Cells
		26.2	 Etiology and Pathogenesis
		26.3	 Clinical Entities
			26.3.1	 Epididymitis
			26.3.2	 Prostatitis
			26.3.3	 Urethritis
			26.3.4	 Infectious and Inflammatory Obstruction of the Seminal Ducts
			26.3.5	 Asymptomatic Infections and Inflammation of the Genital Tract in Infertile Men
		26.4	 Diagnostics
			26.4.1	 Clinical Diagnostics and Imaging Techniques
			26.4.2	 Laboratory Diagnostics
		26.5	 Therapy
		References
	27: Obstructions of the Seminal Ducts, Cystic Fibrosis, and Congenital Aplasia of the Ductus Deferens
		27.1	 Obstruction of the Seminal Ducts
			27.1.1	 Etiology and Pathogenesis
			27.1.2	 Clinic
			27.1.3	 Diagnostics
			27.1.4	 Therapy
		27.2	 Cystic Fibrosis
			27.2.1	 Etiology and Pathogenesis
			27.2.2	 Clinic and Diagnostics
			27.2.3	 Therapy
		27.3	 Congenital Aplasia of the Ductus Deferens (CBAVD)
			27.3.1	 Etiology and Pathogenesis
			27.3.2	 Clinic and Diagnosis
			27.3.3	 Therapy
			27.3.4	 Unilateral Aplasia of the Ductus Deferens
			27.3.5	 Bilateral Obstruction of the Ejaculatory Ducts
		27.4	 Young’s Syndrome
		References
	28: Immunologically Induced Infertility
		28.1	 Definition
		28.2	 Epidemiology
		28.3	 Etiology and Pathogenesis
		28.4	 Clinical Aspects
		28.5	 Diagnostics
		28.6	 Therapy
		References
	29: Andrologically Relevant Changes in the External Genitals
		29.1	 Introduction
		29.2	 Skin Lesions Without Pathological Significance and Benign Neoplasms
			29.2.1	 Papillae Coronae Glandis (Pearly Penile Papules)
				29.2.1.1	 Introduction
				29.2.1.2	 Clinic
				29.2.1.3	 Differential Diagnoses
				29.2.1.4	 Therapy
				29.2.1.5	 Andrological Relevance
			29.2.2	 Heterotopic Sebaceous Glands
				29.2.2.1	 Introduction
				29.2.2.2	 Clinic
				29.2.2.3	 Differential Diagnoses
				29.2.2.4	 Therapy
				29.2.2.5	 Andrologic Relevance
			29.2.3	 Hemangiomas
				29.2.3.1	 Introduction
				29.2.3.2	 Clinic
				29.2.3.3	 Differential Diagnoses
				29.2.3.4	 Therapy
				29.2.3.5	 Andrological Relevance
			29.2.4	 Penile Nevus Cell Nevi
				29.2.4.1	 Introduction
				29.2.4.2	 Clinic
				29.2.4.3	 Differential Diagnoses
				29.2.4.4	 Therapy
				29.2.4.5	 Andrological Relevance
			29.2.5	 Penile Lentiginosis
				29.2.5.1	 Introduction
				29.2.5.2	 Clinic
				29.2.5.3	 Differential Diagnoses
				29.2.5.4	 Therapy
				29.2.5.5	 Andrological Relevance
			29.2.6	 Fibroma Molle
				29.2.6.1	 Introduction
				29.2.6.2	 Clinic
				29.2.6.3	 Differential Diagnoses
				29.2.6.4	 Therapy
				29.2.6.5	 Andrological Relevance
			29.2.7	 Angiokeratomas
				29.2.7.1	 Introduction
				29.2.7.2	 Clinic
				29.2.7.3	 Differential Diagnoses
				29.2.7.4	 Therapy
				29.2.7.5	 Andrological Relevance
			29.2.8	 Median Raphe Cyst
				29.2.8.1	 Introduction
				29.2.8.2	 Clinic
				29.2.8.3	 Differential Diagnoses
				29.2.8.4	 Therapy
				29.2.8.5	 Andrological Relevance
		29.3	 Inflammatory Changes of the External Genitalia
			29.3.1	 Non-Venereal Coronary Lymphangitis or Coronary Phlebitis
				29.3.1.1	 Introduction
				29.3.1.2	 Clinic
				29.3.1.3	 Differential Diagnosis
				29.3.1.4	 Histopathology
				29.3.1.5	 Therapy
				29.3.1.6	 Andrological Relevance
			29.3.2	 Balanitis and Balanoposthitis
				29.3.2.1	 Andrological Relevance
			29.3.3	 Fixed Drug Exanthema
				29.3.3.1	 Andrological Relevance
		29.4	 Specific Diseases of the Skin of the Glans Penis and Praeputium
			29.4.1	 Balanoposthitis Chronica Circumscripta Benigna Plasmacellularis Zoon
				29.4.1.1	 Introduction
				29.4.1.2	 Clinic
				29.4.1.3	 Differential Diagnoses
				29.4.1.4	 Therapy
				29.4.1.5	 Andrologic Relevance
			29.4.2	 Lichen Sclerosus Et Atrophicus
				29.4.2.1	 Introduction
				29.4.2.2	 Clinic
				29.4.2.3	 Differential Diagnoses
				29.4.2.4	 Risks and Prognosis
				29.4.2.5	 Therapy
				29.4.2.6	 Andrological Relevance
			29.4.3	 Balanitis Erosiva Circinata (Circinate Balanitis)
				29.4.3.1	 Introduction
				29.4.3.2	 Clinic
				29.4.3.3	 Therapy
				29.4.3.4	 Andrological Relevance
		29.5	 Genital Involvement in General Skin Diseases
			29.5.1	 Introduction
			29.5.2	 Psoriasis Vulgaris
				29.5.2.1	 Introduction
				29.5.2.2	 Andrological Relevance
			29.5.3	 Atopic Dermatitis
				29.5.3.1	 Introduction
				29.5.3.2	 Andrological Relevance
			29.5.4	 Acne Inversa (Hidradenitis Suppurativa)
				29.5.4.1	 Introduction
				29.5.4.2	 Andrological Relevance
		29.6	 Genital Dermatoses Due to Infections
			29.6.1	 Viral Infections
				29.6.1.1	 Human Papillomaviruses
					29.6.1.1.1 Introduction
					29.6.1.1.2 HPV Types
					29.6.1.1.3 Epidemiology
					29.6.1.1.4 Clinic
					29.6.1.1.5 Differential Diagnoses
					29.6.1.1.6 Diagnostics
					29.6.1.1.7 HPV Screening and Prevention
					29.6.1.1.8 Therapy
					29.6.1.1.9 Vaccination
					29.6.1.1.10 Andrological Relevance
				29.6.1.2	 Herpes Simplex Virus (HSV)
					29.6.1.2.1 Introduction
					29.6.1.2.2 Clinic
					29.6.1.2.3 Differential Diagnosis
					29.6.1.2.4 Therapy
					29.6.1.2.5 Andrological Relevance
				29.6.1.3	 Molluscum Contagiosum Virus
					29.6.1.3.1 Introduction
					29.6.1.3.2 Clinic
					29.6.1.3.3 Differential Diagnoses
					29.6.1.3.4 Therapy
					29.6.1.3.5 Andrological Relevance
			29.6.2	 Fungal Infections
				29.6.2.1	 Candida Albicans
					29.6.2.1.1 Introduction
					29.6.2.1.2 Clinic
					29.6.2.1.3 Differential Diagnoses
					29.6.2.1.4 Therapy
					29.6.2.1.5 Andrological Relevance
				29.6.2.2	 Dermatophytes
					29.6.2.2.1 Introduction
					29.6.2.2.2 Clinic
					29.6.2.2.3 Differential Diagnoses
					29.6.2.2.4 Therapy
					29.6.2.2.5 Andrological Relevance
			29.6.3	 Bacterial Infections
				29.6.3.1	 Syphilis
					29.6.3.1.1 Introduction
					29.6.3.1.2 Clinic
					29.6.3.1.3 Differential Diagnosis
					29.6.3.1.4 Therapy
					29.6.3.1.5 Andrological Relevance
				29.6.3.2	 Gonorrhea
					29.6.3.2.1 Introduction
					29.6.3.2.2 Clinic
					29.6.3.2.3 Differential Diagnosis
					29.6.3.2.4 Therapy
					29.6.3.2.5 Andrological Relevance
				29.6.3.3	 Soft Chancre (Ulcus Molle)
					29.6.3.3.1 Introduction
					29.6.3.3.2 Clinic
					29.6.3.3.3 Differential Diagnosis
					29.6.3.3.4 Therapy
					29.6.3.3.5 Andrological Relevance
				29.6.3.4	 Inguinal Lymphogranuloma
					29.6.3.4.1 Introduction
					29.6.3.4.2 Clinic
					29.6.3.4.3 Differential Diagnosis
					29.6.3.4.4 Therapy
					29.6.3.4.5 Andrological Relevance
				29.6.3.5	 Acute Gangrene of the Male Genitalia (Fournier’s Gangrene)
					29.6.3.5.1 Introduction
					29.6.3.5.2 Clinic
					29.6.3.5.3 Therapy
					29.6.3.5.4 Andrological Relevance
		29.7	 Phimosis
		29.8	 Malignant Changes of the External Genitalia
			29.8.1	 Erythroplasia Queyrat
				29.8.1.1	 Introduction
				29.8.1.2	 Clinic
				29.8.1.3	 Differential Diagnoses
				29.8.1.4	 Therapy
				29.8.1.5	 Andrological Relevance
			29.8.2	 Extramammary Paget’s Disease
				29.8.2.1	 Andrological Relevance
			29.8.3	 Invasive Squamous Cell Carcinoma of the Penis
				29.8.3.1	 Andrological Relevance
		29.9	 Penile Injuries
			29.9.1	 Penile Rupture (“Penile Fracture”)
				29.9.1.1	 Andrological Relevance
			29.9.2	 Side Effects of Penile Augmentation Injections
				29.9.2.1	 Andrological Relevance
			29.9.3	 Self-Injury of the Penis
			29.9.4	 Piercings
		29.10	 Induratio Penis Plastica (Peyronie’s Disease)
			29.10.1	 Introduction
			29.10.2	 Clinic
			29.10.3	 Therapy
			29.10.4	 Andrological Relevance
		29.11	 Congenital Malformations of the Penis
			29.11.1	 Introduction
			29.11.2	 Andrological Relevance
		29.12	 Scrotal Skin Lesions
			29.12.1	 Scrotal Cysts (Scrotal Calcinosis)
				29.12.1.1	 Introduction
				29.12.1.2	 Clinic
				29.12.1.3	 Therapy
				29.12.1.4	 Andrological Relevance
			29.12.2	 Pruritus Scroti
				29.12.2.1	 Introduction
				29.12.2.2	 Clinic
				29.12.2.3	 Therapy
		References
	30: Disorders of Erection, Cohabitation, and Ejaculation
		30.1	 Erectile Dysfunction
			30.1.1	 Definition, Epidemiology, and Risk Factors
			30.1.2	 Anatomy
			30.1.3	 Physiology of Erection
				30.1.3.1	 Hemodynamics
				30.1.3.2	 Neurophysiology
				30.1.3.3	 Cellular Control of Erection
			30.1.4	 Pathophysiology of Erection
				30.1.4.1	 Psychogenic Influences on Erection
				30.1.4.2	 Vascular Erectile Dysfunction
				30.1.4.3	 Neurogenic Erectile Dysfunction
				30.1.4.4	 Endocrine-Related Erectile Dysfunction
				30.1.4.5	 Drug-Induced Erectile Dysfunction
			30.1.5	 Diagnostic Assessment of Erectile Dysfunction
				30.1.5.1	 Anamnesis and Sexual Anamnesis
				30.1.5.2	 Clinical Examination
				30.1.5.3	 Validated Questionnaires
				30.1.5.4	 Laboratory Medical Tests
				30.1.5.5	 Oral Pharmaceutical Test with PDE-5 Inhibitors
				30.1.5.6	 Cavernous Body Pharmacoinjection Test
				30.1.5.7	 Doppler Sonography
				30.1.5.8	 Duplex Sonography
				30.1.5.9	 Penile Angiography
				30.1.5.10	 Venous Outflow Diagnostics
				30.1.5.11	 Neurophysiological Assessment
				30.1.5.12	 Nocturnal Rigidity and Tumescence Measurements
			30.1.6	 Therapy of Erectile Dysfunction
				30.1.6.1	 Lifestyle Modification and Risk Factor Reduction
				30.1.6.2	 Psychological/Psychotherapeutic Interventions
				30.1.6.3	 Hormonal Treatment
				30.1.6.4	 External Erectile Aids
				30.1.6.5	 Oral Therapy
				30.1.6.6	 Topical Therapy
			30.1.7	 Low-Energy Extracorporeal Shock Wave Therapy (“Low-Intensity Shock Wave” Therapy)
				30.1.7.1	 Intracavernous Auto-Injection Therapy
				30.1.7.2	 Surgical Treatment
					30.1.7.2.1	Vein Surgery
					30.1.7.2.2	Revascularization Surgery
		30.2	 Ejaculation Disorders
			30.2.1	 Anejaculation and Retrograde Ejaculation
				30.2.1.1	 Diagnostics
				30.2.1.2	 Therapy
			30.2.2	 Premature Ejaculation
				30.2.2.1	 Epidemiology
				30.2.2.2	 Diagnostics
				30.2.2.3	 Therapy
		30.3	 Penile Abnormalities
			30.3.1	 Hypospadias and Epispadias
			30.3.2	 Phimosis
			30.3.3	 Penile Deviation
				30.3.3.1	 Congenital Penile Deviation
				30.3.3.2	 Peyronie’s Disease
					30.3.3.2.1	Definition and Pathophysiology
					30.3.3.2.2	Epidemiology and Risk Factors
					30.3.3.2.3	Clinical Findings
					30.3.3.2.4	Diagnostics
					30.3.3.2.5	Therapy
						Conservative Therapy
						Oral Pharmacotherapy
						Intralesional Injection
						Low-Intensity Extracorporeal Shock Wave Therapy (Li-ESWT)
						Penile Traction Therapy
						Surgical Therapy
						Penile Prosthesis Implantation
		30.4	 Priapism
			30.4.1	 Definition and Epidemiology
			30.4.2	 Classification and Clinical Findings
			30.4.3	 Ischemic Priapism
			30.4.4	 Etiology and Risk Factors
			30.4.5	 Recurrent Priapism
			30.4.6	 Nonischemic Priapism
			30.4.7	 Diagnostics
			30.4.8	 Laboratory Tests
			30.4.9	 Sonography
			30.4.10 MRI
			30.4.11 Therapy
				30.4.11.1	 Therapy of Ischemic Priapism
					30.4.11.1.1	Nonsurgical Therapy
					30.4.11.1.2	Surgical Therapy
				30.4.11.2	 Therapy of Nonischemic Priapism
					30.4.11.2.1	Conservative Therapy Methods
					30.4.11.2.2	Surgical Therapeutic Procedures
					30.4.11.2.3	Therapy of Recurrent Priapism
		References
Part VI: Clinics in Andrology: Disorders of Sexual Differentiation and Androgen Target Organs
	31: Variants of Sex Development
		31.1	 Introduction
		31.2	 Nomenclature and Classification
			31.2.1	 The Classification of DSD
		31.3	 Clinical Examination and Medical Classification
		31.4	 Structural Chromosomal Abnormalities
			31.4.1	 Definition and Etiology
			31.4.2	 Diagnosis
			31.4.3	 Therapy
		31.5	 46,XX Men (with 21-Hydroxylase Deficiency)
			31.5.1	 Definition and Etiology
			31.5.2	 Diagnosis
			31.5.3	 Therapy
		31.6	 46XY-DSD
			31.6.1	 Gonadal Dysgenesis
				31.6.1.1	 Definition and Etiology
				31.6.1.2	 Diagnosis
				31.6.1.3	 Therapy
			31.6.2	 Gonadal Dysgenesis Due to SRY Mutation (Yp11.3)
			31.6.3	 Gonadal Dysgenesis Due to SF1/NR5A1 Mutations (9q33)
			31.6.4	 Gonadal Dysgenesis Due to WT-1 Mutations (11p13)
			31.6.5	 Gonadal Dysgenesis Due to Deletion of the DMRT1 Gene Locus (9p-)
			31.6.6	 SOX9 (17q24), DAX1 (Xp21.3), DHH (12q13.1), WNT4 (1p35)
		31.7	 46,XY-DSD Caused by Defects in Androgen Biosynthesis
			31.7.1	 17ß-Hydroxysteroid Dehydrogenase Type 3 Defect (9q22)
			31.7.2	 5α-Reductase Type 2 Defect (2p23) = Perineoscrotal Hypospadias with Pseudovagina
			31.7.3	 Gonadotropin Receptor Mutations
				31.7.3.1	 LH Receptor Defect (2p21) or Inactivating LH Receptor Mutations
				31.7.3.2	 Activating LH Receptor Mutations
				31.7.3.3	 Inactivating and Activating FSH Receptor Mutations
		31.8	 Disorders of Androgen Action
			31.8.1	 Definition and Etiology
			31.8.2	 Diagnosis
			31.8.3	 Therapy
			31.8.4	 Complete Androgen Insensitivity Syndrome (CAIS)
			31.8.5	 Partial Androgen Insensitivity Syndrome (PAIS)
			31.8.6	 Minimal Androgen Insensitivity Syndrome (MAIS)
		31.9	 Persistent Müllerian Duct Syndrome
		31.10	 Vanishing Testis Syndrome
		31.11	 Ovotesticular DSD
			31.11.1	 Definition and Etiology
			31.11.2	 Diagnosis
			31.11.3	 Therapy
		References
	32: Gynecomastia
		32.1	 Definition of a Multicausal Symptom
		32.2	 Prevalence of Gynecomastia
		32.3	 Pathophysiology
		32.4	 Psychosocial Aspects
		32.5	 Diagnostics
			32.5.1	 Clinical Examination
			32.5.2	 Laboratory Diagnostics
			32.5.3	 Imaging Diagnosis
		32.6	 Clinical Pictures
			32.6.1	 “Physiological” Gynecomastia
			32.6.2	 Gynecomastia due to Reduced Androgen Production
			32.6.3	 Gynecomastia due to Androgen Insensitivity
			32.6.4	 Gynecomastia due to Increased Estrogen Production
			32.6.5	 Gynecomastia Caused by Drugs
			32.6.6	 Gynecomastia Due to Food and Cosmetics
		32.7	 Male Breast Cancer
		32.8	 Therapy
		References
	33: Male Androgenetic Alopecia
		33.1	 Epidemiology
		33.2	 Pathophysiology
		33.3	 Genetics
		33.4	 Diagnostics
		33.5	 Therapy
			33.5.1	 5-Alpha-Reductase Inhibitors: Finasteride and Dutasteride
			33.5.2	 Minoxidil
			33.5.3	 Laser Therapies
			33.5.4	 Hair and Stem Cell Transplantation
			33.5.5	 Other Therapeutic Approaches
		References
Part VII: Clinics in Andrology: Disorders of Reproductive Health Caused by Environmental and Systemic Diseases
	34: Testicular Dysfunction in Systemic Diseases
		34.1	 Background
		34.2	 Mechanisms of Reproductive Disruption by Systemic Diseases
			34.2.1	 Onset of Hypogonadism, Sexual Dysfunction, and Spermatogenic Failure
			34.2.2	 Level of Disruption in the Male Reproductive Axis
		34.3	 Specific Diseases and Disorders
			34.3.1	 Renal Disease
			34.3.2	 Liver Disease
			34.3.3	 Respiratory Diseases
			34.3.4	 Malignant Disease
				34.3.4.1	 Surgery
				34.3.4.2	 Chemo-/Radiotherapy
				34.3.4.3	 Immunotherapy
			34.3.5	 Neurological Diseases
				34.3.5.1	 Genetic Disorders
				34.3.5.2	 Acquired Disorders
			34.3.6	 Gastrointestinal Diseases
			34.3.7	 Hematological Diseases
			34.3.8	 Endocrine and Metabolic Diseases
			34.3.9	 Immune Diseases
			34.3.10 Infectious Diseases
			34.3.11 Cardiovascular Diseases
			34.3.12 Dermatological Diseases
			34.3.13 Other Chronic Diseases
		34.4	 Therapeutic Implications
		References
	35: Environmental Influences on Male Reproductive Health
		35.1	 Introduction
		35.2	 Potential Adverse Effects on Spermatogenesis
			35.2.1	 Cell Death
			35.2.2	 Genetic Change
				35.2.2.1	 DNA Repair in the Germline
			35.2.3	 Epigenetics in Spermatogenic Cells
		35.3	 Common Threats to Male Reproduction
			35.3.1	 General
			35.3.2	 Smoking
			35.3.3	 Ionising Radiation
			35.3.4	 Electromagnetic Radiation
			35.3.5	 Cancer Therapies
			35.3.6	 Heat
			35.3.7	 Ageing
			35.3.8	 Occupational Exposures
			35.3.9	 Toxic Mixtures
		35.4	 Developmental Reproductive Toxicity
			35.4.1	 Cryptorchidism
			35.4.2	 Hypospadia
			35.4.3	 Testicular Cancer
			35.4.4	 Semen Quality
			35.4.5	 Hormone Levels
		35.5	 Design and Interpretation of Toxicological Studies
			35.5.1	 Design of Non-Human Studies
			35.5.2	 Design of Human Studies
			35.5.3	 Regulatory Testing for Reproductive Toxicity
				35.5.3.1	 Regulatory Reproductive Research Strategies
				35.5.3.2	 Regulatory Reproductive Research Strategies
					35.5.3.2.1 Experimental Methods in Male Reproductive Research
		35.6	 Future Perspectives
			35.6.1	 Experimental Studies
				35.6.1.1	 Non-Human Studies
				35.6.1.2	 Human Studies
			35.6.2	 Clinical Implications
				35.6.2.1	 Clinical Practice
		References
Part VIII: Andrological Therapy
	36: Therapy with Testosterone
		36.1	 Overview of Indications and Preparations
		36.2	 Pharmacology of Testosterone Preparations
			36.2.1	 Oral Testosterone Preparations
				36.2.1.1	 Testosterone Undecanoate
				36.2.1.2	 Methyltestosterone and Fluoxymesterone
				36.2.1.3	 Mesterolone
			36.2.2	 Buccal Forms of Administration
			36.2.3	 Intramuscular Testosterone Preparations
				36.2.3.1	 Testosterone Enanthate
				36.2.3.2	 Testosterone Propionate
				36.2.3.3	 Testosterone Undecanoate
			36.2.4	 Transdermal Testosterone Preparations
				36.2.4.1	 Testosterone Patches
				36.2.4.2	 Testosterone Gels
				36.2.4.3	 Transdermal Dihydrotestosterone
			36.2.5	 Testosterone Implants
			36.2.6	 Nasal Testosterone Preparations
		36.3	 Contraindications for Testosterone Therapy
		36.4	 Monitoring Testosterone Therapy in Hypogonadism
			36.4.1	 Psyche and Sexuality
			36.4.2	 Somatic Parameters
			36.4.3	 Laboratory Parameters
			36.4.4	 Prostate and Seminal Vesicles
			36.4.5	 Bone and Muscle
		36.5	 Evaluation of Testosterone Replacement Therapy in Hypogonadism
		36.6	 Testosterone Therapy for Excessively Tall Stature
		References
	37: Abuse of Anabolic Androgenic Steroids (AAS) for Doping
		37.1	 Dimension of the Problem/Epidemiology
		37.2	 Chemistry and Detection
		37.3	 Side Effects on Reproductive Functions (Table 37.2)
			37.3.1	 Specific Side Effects in Men
			37.3.2	 Specific Side Effects in Women
				37.3.2.1	 Hypothalamic-Pituitary-Gonadal Axis
				37.3.2.2	 Hirsutism
				37.3.2.3	 Changes in the Voice
		37.4	 Effects on Nonreproductive Organs (Table 37.3)
			37.4.1	 Hematological Side Effects
			37.4.2	 Side Effects on the Cardiovascular System
				37.4.2.1	 Arrhythmias
				37.4.2.2	 Myocardial Hypertrophy
				37.4.2.3	 Sudden Cardiac Death
				37.4.2.4	 Dilated Cardiomyopathy (DCM)
				37.4.2.5	 Arterial Hypertension
				37.4.2.6	 Atherosclerosis
			37.4.3	 Liver Disease
			37.4.4	 Nephropathies
			37.4.5	 Influence on the Musculoskeletal System
			37.4.6	 Dermatological Side Effects
			37.4.7	 Neoplasms
			37.4.8	 Side Effects on the Psyche
		References
	38: Treatment of Hypogonadism of Hypothalamic or Pituitary Origin
		38.1	 Hormonal Treatment of Hypogonadotropic Hypogonadism (HH)
			38.1.1	 Comparison GnRH Versus Gonadotropins
			38.1.2	 Replacement of GnRH
				38.1.2.1	 Treatment Protocol for GnRH Replacement
			38.1.3	 Replacement of Gonadotropins
				38.1.3.1	 Treatment Protocol for Gonadotropin Replacement in Testosterone-Naïve Prepubescent Adolescents with Congenital Hypogonadotropic Hypogonadism (CHH)
				38.1.3.2	 Treatment Protocol for Gonadotropin Replacement in Adolescents with HH, Previously Virilized by Testosterone
				38.1.3.3	 Hormone Replacement in Men with Postpubertally Acquired HH
		38.2	 Monitoring of Hormone Replacement and Cryostorage of Semen
		38.3	 Success Rates
		38.4	 Therapeutic Options in the Case of Persistent Azoospermia
		38.5	 Pregnancy Rates
		38.6	 Inheritance of Congenital Hypogonadotropic Hypogonadism
		38.7	 Misdiagnosis of Constitutional Delay of Growth and Puberty (CDGP) as CHH and “CHH Reversal”
		38.8	 Treatment of Functional HH
			38.8.1	 Treatment of Functional HH Due to Excessive Weight Loss or Obesity
			38.8.2	 Treatment of Functional HH Resulting from Drug-Induced Suppression of the Hypothalamic-Pituitary-Gonadal (HPG) Axis
		References
	39: Therapeutic Attempts in Idiopathic Infertility
		39.1	 Definition and Incidence of Idiopathic Infertility
		39.2	 Empirical Therapy
			39.2.1	 Gonadotropins: hCG/hMG/rFSH
			39.2.2	 Antiestrogens and Aromatase Inhibitors
				39.2.2.1	 Antiestrogens
				39.2.2.2	 Aromatase Inhibitors
			39.2.3	 Antioxidants, Diets, and Supplements with Antioxidant Effects: Vitamins, Folic Acid, Zinc, Carnitine, and Others
				39.2.3.1	 Diets
			39.2.4	 Herbs from Natural Medicine
			39.2.5	 Pentoxifylline /Theophylline
			39.2.6	 Antibiotics and Anti-Inflammatory Drugs
			39.2.7	 Historical Deviations: Mesterolone, Pulsatile GnRH, Kallikrein, etc.
		39.3	 Therapeutic Guideline
		References
	40: Gynecology Relevant to Andrology
		40.1	 Medical History and Somatic Factors
			40.1.1	 Age
			40.1.2	 Coital Frequency
			40.1.3	 Length of Childlessness
			40.1.4	 Risk of Infection
			40.1.5	 Psychological Factors
				40.1.5.1	 Libido Dysfunction and Orgasmic Disturbances
				40.1.5.2	 Dyspareunia
			40.1.6	 Hormones and Female Sexuality
			40.1.7	 Stress
				40.1.7.1	 Immunological Modulation and Stress
			40.1.8	 Environmental Factors
				40.1.8.1	 Definitions
				40.1.8.2	 Epidemiology
				40.1.8.3	 Nicotine
				40.1.8.4	 X-Rays and Radioactivity
				40.1.8.5	 Electromagnetic Fields
			40.1.9	 Pertinent Medical History
				40.1.9.1	 Physiology of Pregnancy
				40.1.9.2	 Pertinent Medical Disorders
					40.1.9.2.1 Pulmonary Disease
		40.2	 Ovarian Cycle and Ovulation
			40.2.1	 Follicles
				40.2.1.1	 Early Oocyte Development
				40.2.1.2	 Meiosis
				40.2.1.3	 Follicle Development
				40.2.1.4	 Regulatory Mechanisms
			40.2.2	 Menstrual Cycle
				40.2.2.1	 Hormone Variations
				40.2.2.2	 Luteal Phase
				40.2.2.3	 Ovulation
				40.2.2.4	 Changes in the Uterine Cervix and in Cervical Mucus Production
				40.2.2.5	 Endometrium
				40.2.2.6	 Vaginal Epithelium
			40.2.3	 Diagnostic Evaluation of the Cycle
				40.2.3.1	 Ultrasound
				40.2.3.2	 Endometrial Evaluation
				40.2.3.3	 LUF Syndrome
				40.2.3.4	 Endometrial Biopsy
				40.2.3.5	 Progesterone Levels and Evaluation of Luteal Quality
			40.2.4	 Impairment of Follicle Maturation
				40.2.4.1 Amenorrhea
				40.2.4.2	 Primary Amenorrhea
				40.2.4.3	 Secondary Amenorrhea
				40.2.4.4	 Hyperprolactinemia
				40.2.4.5	 Pituitary Adenoma
				40.2.4.6	 Empty Sella Syndrome
				40.2.4.7	 Surgical and Radiological Treatment of Hyperprolactinemia
				40.2.4.8	 Pharmacological Treatment
				40.2.4.9	 Polycystic Ovarian Disease
				40.2.4.10	 Hyperandrogenemia
				40.2.4.11	 Chronic Anovulation
				40.2.4.12	 Polycystic Ovaries Confirmed by Ultrasound
				40.2.4.13	 Insulin Resistance
				40.2.4.14	 Obesity
				40.2.4.15	 Causes and Risk Factors
				40.2.4.16	 Diagnosis
				40.2.4.17	 Treatment
				40.2.4.18	 hMG and FSH
				40.2.4.19	 GnRH Downregulation
				40.2.4.20	 Pulsatile GnRH Treatment (LutrePulse® System)
				40.2.4.21	 Ovarian Wedge Resection
				40.2.4.22	 Reduced Body Weight and Follicular Maturation
				40.2.4.23	 Primary Ovarian Failure
				40.2.4.24	 Autoimmune Diseases
				40.2.4.25	 Treatment
		40.3	 Infertility Due to Disturbances of Gamete Migration
			40.3.1	 Vagina and Cervix
			40.3.2	 Anomalies of the Female Genital Tract
				40.3.2.1	 Uterus
				40.3.2.2	 Fallopian Tubes
			40.3.3	 Physiology of Tubal Function
			40.3.4	 Diseases of the Fallopian Tubes
				40.3.4.1	 Salpingitis
			40.3.5	 Diagnostic Tests for Uterine and Tubal Patency
				40.3.5.1	 Tubal Insufflation
				40.3.5.2	 Hysterosalpingography
				40.3.5.3	 Hysteroscopy and Laparoscopy
			40.3.6	 Treatment
		40.4	 Endometriosis
			40.4.1	 Pathogenesis and Epidemiology
			40.4.2	 Symptoms
			40.4.3	 Pathophysiology
			40.4.4	 Staging of Endometriosis
			40.4.5	 Treatment
				40.4.5.1	 GnRH Analogs
				40.4.5.2	 Aromatase Inhibitors
				40.4.5.3	 Surgical Treatment
				40.4.5.4	 IVF
		40.5	 Sperm Antibodies
			40.5.1	 Pathophysiology
			40.5.2	 Antibody Testing
			40.5.3	 Treatment
		40.6	 Early Pregnancy Abnormalities
			40.6.1	 Implantation
			40.6.2	 Pregnancy Loss
		40.7	 Idiopathic Infertility
		40.8	 Prospects and Conclusion
		References
	41: Assisted Reproduction
		41.1	 Assisted Reproduction as a Treatment of Infertility
		41.2	 Methods of Medically Assisted Reproduction for the Treatment of Male Infertility
		41.3	 Likelihood of Natural Conception after Long-Term Infertility
		41.4	 Medically Assisted Reproduction (MAR)
			41.4.1	 Intrauterine Insemination (IUI)
			41.4.2	 In Vitro Fertilization (IVF)
			41.4.3	 Intracytoplasmic Sperm Injection (ICSI)
			41.4.4	 Semen Donation
		41.5	 Collection and Preparation of Sperm
			41.5.1	 Collection of Semen
			41.5.2	 Basics of Sperm Preparation
			41.5.3	 The Swim-Up Method
			41.5.4	 Density Gradient Centrifugation
			41.5.5	 Removal of Infectious Viral Particles from the Semen
			41.5.6	 Sorting of Spermatozoa Based on Predefined Characteristics
				41.5.6.1	 Selection of Sperm with Flow Cytometry and Sorting (FACS) Based on the Sex Chromosomes
				41.5.6.2	 Selection of Spermatozoa Through Binding to Hyaluronidase
				41.5.6.3	 Sorting Based on the Morphology of Spermatozoa
				41.5.6.4	 Selection of Normal Spermatozoa Based on Exclusion of Spermatozoa with Fragmented DNA
			41.5.7	 Chemical Treatment of Spermatozoa in Culture
		41.6	 Ovarian Follicular Development, Ovarian Stimulation, and Ovulation Induction
			41.6.1	 Monitoring of Ovarian Follicular Development and Ovarian Stimulation for Insemination
			41.6.2	 Ovarian Stimulation for IVF and ICSI
				41.6.2.1	 Planning the Treatment
				41.6.2.2	 Ovarian Hyperstimulation with Exogenous Gonadotropin Preparations
				41.6.2.3	 Ovulation Induction
			41.6.3	 Oocyte Collection
			41.6.4	 Embryo Transfer
				41.6.4.1	 Luteal Phase Support
			41.6.5	 Cryopreservation of Oocytes in the Pronucleate Stage and of Embryos
		41.7	 Complications of Medically Assisted Reproduction
			41.7.1	 Short-Term Complications of Assisted Reproduction
			41.7.2	 Complications During Pregnancy
			41.7.3	 Long-Term Complications for the Mother
			41.7.4	 Pediatric Aspects of Assisted Reproduction
		References
	42: Cryopreservation of Human Sperm and Testicular Germ Cell Tissue for Fertility Reserve
		42.1	 Cryopreservation of Sperm and Testicular Tissue for Fertility Protection and Fertility Reserve
			42.1.1	 Historical Development of Sperm Cryopreservation from Ejaculate and Testicular Tissue
			42.1.2	 Emergence of the “Androprotect®” Network: Cryopreservation of Immature Germ Cell Tissue (Spermatogonial Stem Cells)
			42.1.3	 Guidelines and Legal Framework for Sperm and Germ Cell Tissue Cryopreservation
		42.2	 Indications for Cryopreservation of Sperm and Testicular Tissue
			42.2.1	 Oncological Diseases and Gonadotoxic Therapies in Adults and Adolescents
			42.2.2	 Oncological and Non-Oncological Diseases in Children
			42.2.3	 Cryopreservation in Congenital Diseases with Gonadal Damage
			42.2.4	 Cryopreservation in Spinal Cord Lesions
			42.2.5	 Cryopreservation in the Context of Infertility Diagnosis and Therapy
			42.2.6	 Fertility Protection in Transpersons (Transwomen)
			42.2.7	 Cryopreservation Before Vasectomy or After Vasovasostomy (VV) (or Vasotubulostomy (VT))
			42.2.8	 Cryopreservation for Nonmedical Indication (“Social Freezing”)
			42.2.9	 Sperm Donation
		42.3	 Sperm Analysis, Processing, and Cryopreservation
		42.4	 Analysis, Processing, and Cryopreservation of Spermatogonial Stem Cells (Androprotect®)
		42.5	 Safety and Quality Requirements and Risk Assessment in the Context of Cryopreservation of Human Germ and Spermatogonial Stem Cells
			42.5.1	 Safety and Quality Control Measures
			42.5.2	 Handling of (Potentially) Infectious Specimens
			42.5.3	 Risk of Tumor Cell Contamination of Spermatogonial Stem Cells
		42.6	 Use and Quality of Cryopreserved and Stored Spermatozoa and Germ Cell Tissue
			42.6.1	 Use of Cryopreserved Sperm Cells from Ejaculate and Germ Cell Tissue
			42.6.2	 Experimental Use of Immature Germ Cell Tissue
			42.6.3	 Quality Assessment of Immature Germ Cell Tissue
				42.6.3.1	 Histological Evaluation of Immature Testicular Tissues
				42.6.3.2	 The Androprotect® Score
		42.7	 Prospects, Limitations, and Risks of Cryopreservation
			42.7.1	 Prospects for Success and Risks for Later Paternity
			42.7.2	 Genetic Risk for Offspring
			42.7.3	 Experimental Use of Spermatogonial Stem Cells and Their Prospects for Clinical Application
			42.7.4	 Psychological Aspects
		References
Part IX: Sexual Health
	43: Sexual Medicine and Andrology
		43.1	 Sexual Medicine in Clinical Practice
		43.2	 Basic Understanding of Human Sexuality
		43.3	 The Spectrum of Sexual Disorders
			43.3.1	 Disorders of Sexual Function
				43.3.1.1	 Disorders of Sexual Desire
				43.3.1.2	 Disorders of Sexual Arousal
				43.3.1.3	 Disorders of Orgasm
				43.3.1.4	 Sexual Dysfunctions Due to Illness and/or Treatment
			43.3.2	 Disorders of Sexual Development
				43.3.2.1	 Disorder of Sexual Maturation
				43.3.2.2	 Disorders of Sexual Orientation
				43.3.2.3	 Disorders of Sexual Identity
				43.3.2.4	 Disorders of Sexual Relationship
			43.3.3	 Disorders of Gender Identity (Gender Dysphoria/Gender Incongruence)
			43.3.4	 Disorders of Sexual Preference (Paraphilic Disorders)
			43.3.5	 Disorders of Sexual Behavior (Dissexuality)
			43.3.6	 Disorders of Sexual Reproduction
		43.4	 Principles of Diagnosis in Sexual Medicine
			43.4.1	 Exploration of a Sexual Disorder
			43.4.2	 Exploration of the Three Dimensions of Sexuality
				43.4.2.1	 The Dimension of Attachment
				43.4.2.2	 The Dimension of Reproduction
				43.4.2.3	 The Dimension of Desire
				43.4.2.4	 Individual and Partner-Related Interaction of These Three Dimensions
			43.4.3	 Medical History and Somatic Findings
		43.5	 Principles of Therapy in Sexual Medicine
			43.5.1	 Sexual Counseling
			43.5.2	 Sex Therapy
			43.5.3	 Integration of Somatic Therapy Options
			43.5.4	 Treatment of Disorders of Sexual Preference and Behavior
		References
	44: Involuntary Childlessness from the Perspective of Sexual Medicine
		44.1	 Couple-Related Effects of Involuntary Childlessness
		44.2	 Importance of the Dimension of Reproduction
			44.2.1	 Biological Influencing Factors
			44.2.2	 Psychosocial Influencing Factors
			44.2.3	 Conflict Processing Via Reproduction
			44.2.4	 Clinical Case Studies
				44.2.4.1	 “Unbearable Pressure”
				44.2.4.2	 “Pregnant Even as a Man”
				44.2.4.3	 “It’s Now or Never”.
		44.3	 Expanded Concept of Sexuality in Fertility Treatment
		44.4	 Indication for Couple-Related Interventions
		References
Part X: Male Contraception
	45: Male Contribution to Contraception
		45.1	 Introduction
		45.2	 Requirements and Perspectives
			45.2.1	 Global Goal: “Sexual and Reproductive Health”
			45.2.2	 Contraception, Family Planning, and World Population
			45.2.3	 Acceptability of Male Contraception
			45.2.4	 Possibilities
		45.3	 Existing Methods
			45.3.1	 Coitus Interruptus
			45.3.2	 Periodic Abstinence
			45.3.3	 Condoms
		References
	46: Vasectomy
		46.1	 History of Vasectomy
		46.2	 Social and Demographic Relevance
		46.3	 Indications for Vasectomy
		46.4	 Informed Consent
		46.5	 Surgical Vasectomy Techniques
		46.6	 Technical Modifications
		46.7	 Effectiveness and Cost Efficiency
		46.8	 Complications
		46.9	 Vasectomy and Long-Term Morbidity
		46.10	 Psychosexual Effects
		46.11	 Refertilization
			46.11.1	 History of Refertilization Surgery
			46.11.2	 Current Demand and Frequency of Refertilization
			46.11.3	 Vasovasostomy
				46.11.3.1	 Indications, Counseling, Consent, and Costs
				46.11.3.2	 Vasovasostomy Technique
				46.11.3.3	 Results of Vasovasostomy
				46.11.3.4	 Complications Following Vasovasostomy
			46.11.4	 Epididymovasostomy
			46.11.5	 Future Developments in Surgical Refertilization
		46.12	 Future Development of Vasectomy
		References
	47: Approaches to Hormonal Male Contraception
		47.1	 Principle of Hormonal Male Contraception
		47.2	 Androgens Alone
			47.2.1	 Testosterone Enanthate
			47.2.2	 Testosterone Buciclate
			47.2.3	 Testosterone Undecanoate
			47.2.4	 Testosterone Implants
			47.2.5	 19-Nortestosterone
			47.2.6	 7α-Methyl-19-Nortestosterone
			47.2.7	 Dimethandrolone Undecanoate and 11β-Methyl-19-Nortestosterone Dodecylcarbonate
		47.3	 Androgens in Combination with GnRH Analogues
			47.3.1	 GnRH Agonists
			47.3.2	 GnRH Antagonists
		47.4	 Androgens Combined with Progestins
			47.4.1	 Depot Medroxyprogesterone Acetate
			47.4.2	 Levonorgestrel
			47.4.3	 Norethisterone
			47.4.4	 Cyproterone Acetate
			47.4.5	 Desogestrel and Etonogestrel
			47.4.6	 Nestorone®
		47.5	 Conclusion and Outlook
		References
	48: Non-Hormonal Approaches to Male Contraception
		48.1	 Introduction
		48.2	 Principles of Non-Hormonal Contraception
			48.2.1	 Systemic
			48.2.2	 Nonsystemic
		48.3	 Sperm Production
			48.3.1	 Sperm-Specific Targets
				48.3.1.1	 Retinoic Acid Pathway
					48.3.1.1.1 RARα
					48.3.1.1.2 BDAD and ALDH1A
				48.3.1.2	 Testis-Specific Bromodomain (BRDT)
			48.3.2	 Small-Molecule Inhibitors
				48.3.2.1	 Inhibition of Sertoli–Germ Cell Adhesion (Adjudin, Gamendazole, and Indenopyridines)
		48.4	 Sperm Function
			48.4.1	 Sperm-Specific Targets
				48.4.1.1	 Ion Channels
				48.4.1.2	 Immobilization–Motility
				48.4.1.3	 Sperm–Egg Interaction
		48.5	 Sperm Production, Maturation, and/or Function
		48.6	 Antibody, mRNA, and Immunocontraceptives
		48.7	 Natural Products
		48.8	 Sperm Transport–Physical Blockage
		48.9	 Contraceptive Database
		48.10	 Conclusion
		References
Part XI: Law and Ethics in Reproductive Medicine
	49: Legal Regulations in Andrology and Reproductive Medicine
		49.1	 General Part
			49.1.1	 Regulations on Medical Law
			49.1.2	 Prerequisites for Medical Treatment
			49.1.3	 Prerequisites for Medical Research
			49.1.4	 Medical Liability and Insurance
		49.2	 Special Legal Aspects
			49.2.1	 Preventing Pregnancies
				49.2.1.1	 Legal Framework
				49.2.1.2	 Castration
				49.2.1.3	 Sterilization
				49.2.1.4	 Medical Liability
			49.2.2	 Inducing Pregnancy (Assisted Reproduction)
				49.2.2.1	 Introduction: Diversity of Applicable Legal Norms
				49.2.2.2	 Sperm Donation in the Homologous and Heterologous System
				49.2.2.3	 Law of Parenthood
				49.2.2.4	 Physician Liability
				49.2.2.5	 Cost Coverage by Private and Statutory Health Insurance
			49.2.3	 Preimplantation Genetic Diagnosis
			49.2.4	 Cryopreservation
			49.2.5	 Egg Donation, Embryo Donation, and Surrogate Motherhood
			49.2.6	 Research with Embryos and Embryonic Stem Cells
		References
	50: Ethical Criteria of Reproductive Medicine
		50.1	 Questions Under Consideration
		50.2	 Aspects of Medical and Cultural History
		50.3	 Particular Aspects of Reproductive Treatment Options
		50.4	 Normative Criteria
			50.4.1	 Self-Determination
			50.4.2	 Health Protection
			50.4.3	 Child Welfare
			50.4.4	 A Further Aspect: The Status of Embryos Prior to Nidation
		50.5	 Treatment Options of Reproductive Medicine from an Ethical Standpoint
			50.5.1	 Extracorporeal Creation of Embryos in a Homologous Setting
				50.5.1.1	 Intracytoplasmic Sperm Injection
				50.5.1.2	 Medical Freezing
				50.5.1.3	 Other Quasi-Homologous Case Constellations
					50.5.1.3.1 Social Freezing
					50.5.1.3.2 Postmortem Insemination
				50.5.1.4	 Preimplantation Diagnostics
			50.5.2	 Extracorporeal Creation of Embryos in a Heterologous Context
				50.5.2.1	 Sperm Donation
				50.5.2.2	 Oocyte Donation
				50.5.2.3	 Surrogacy
		50.6	 Hypothetical Treatment Options
			50.6.1	 Germline Therapy
			50.6.2	 The Use of Stem Cells
		50.7	 Research on Reproductive Health: Ethically Required
		50.8	 The Role of Religions
			50.8.1	 Opposing Views
			50.8.2	 The Difficulties of Religious Viewpoints
		References
Index