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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

neuroendocrine prostate cancer --- castration-resistant prostate cancer --- androgen deprivation therapy (ADT) --- new therapy --- treatment resistance

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There is extensive evidence from animal models that gonadal steroids, produced in fetal and neonatal life, act on the developing organism to produce sex differences far beyond the reproductive system. That early gonadal steroid exposure also plays an important role in human development is supported by studies of individuals with disorders of sex determination and differentiation. It is much less clear whether normal variation in gonadal steroid exposure predicts sexually dimorphic health outcomes or within-sex variation. This is largely due to challenges related to the assessment of gonadal steroid exposure in the developing fetus and neonate. Regarding the prenatal period, serial measurements of serum hormone levels in the fetus, for use in studies of later development, are not possible for ethical reasons. Researchers have measured hormones in maternal blood, umbilical cord blood, and amniotic fluid; used putative anthropometric indices such as the relative lengths of the 2nd and 4th digits (2D:4D); evaluated common variants in genes related to hormone production, transport, and metabolism; and examined development in opposite sex twins and the offspring of mothers with hyperandrogeny. Each of these approaches has particular strengths and notable weaknesses. Regarding the neonatal period, serial measurements in serum are often impractical for studies of typical development. Salivary hormone assays, frequently used in studies of older children and adults, have not been extensively investigated in neonates. The most appropriate timing for testing is also open to debate. Early work suggested that testosterone levels in males begin to rise after the first postnatal week, peak around the 3rd to 4th months of life, and then drop back to very low levels by 1 year. However a more recent study of 138 infants did not demonstrate this pattern. Testosterone was highest on the day of birth and gradually dropped over the first 6 months. Even less is known about patterns of early estrogen exposure, though highly sensitive bioassays indicated that sex differences are present in early childhood. In addition, the design and interpretation of studies may be impacted by widespread acceptance of conceptual frameworks that are not well-supported empirically. For example, many researchers presume that the free hormone hypothesis, which states that unbound hormone is more readily diffusible into tissues and thus a better measure of actual exposure, is true. However this hypothesis has been challenged on multiple grounds. A second example: it is generally accepted that masculinization of the human brain is primarily mediated by the androgen receptor (in contrast to rodents where the estrogen receptor plays a major role), in part because chromosomal males with complete androgen insensitivity generally espouse a female gender identity. However this is not always the case, and other sexually dimorphic outcomes have not been carefully assessed in CAIS. The aim of this research topic is to gather together experimental and review papers which address the diverse challenges in assessing prenatal and neonatal gonadal steroid exposure for studies of human development with the expectation that this will allow more critical appraisal of existing studies, identify critical research gaps, and improve the design of future studies.

Endocrinology. --- minipuberty --- Testosterone --- androgen receptor --- digit ratio --- prenatal --- sexual differentiation --- umbilical cord blood --- Opposite-sex twins --- Saliva --- Hypogonadism

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This book is a practical clinical guide to the correct diagnosis and appropriate treatment of hyperandrogenism, an extremely common endocrine disease that can affect women from adolescence to menopause. The volume covers topics ranging from the causes to the treatment, providing an expert point of view on the assessment and the differential diagnosis. Since the hyper androgenic syndromes are often associated with menstrual disorders, it is a valuable and easy-to-use resource, not only for endocrinologists but for gynecologists as well. Thanks to its clear approach, it is also useful for all specialists who deal with this women’s disease.

Gynecology. --- Endocrinology. --- Internal medicine --- Hormones --- Gynaecology --- Medicine --- Generative organs, Female --- Diseases --- Gynecology . --- Endocrinology . --- Hyperandrogenism. --- Androgen excess disorders --- Androgens --- Endocrine gynecology --- Adrenogenital syndrome --- Polycystic ovary syndrome --- Pathophysiology

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Sex steroids, including androgens, estrogens, and progestogens, are knownto have widespread physiological actions beyond the reproductive systemvia binding to the sex hormone receptors. Meanwhile, emerging evidence hasindicated that sex hormone receptor signals are involved in the outgrowth ofsome malignancies, such as prostate and breast carcinomas, as well as othersthat have not traditionally been considered as endocrine-related neoplasms. ThisSpecial Issue “Sex Hormone Receptor Signals in Human Malignancies” coversvarious aspects of the potential role of sex hormone receptors and related signalsin prostate cancer, breast cancer, and other neoplastic conditions by depictingpromising findings derived from in vitro and in vivo experiments as well as theanalyses of surgical specimens. The current observations described may thusprovide a unique insight into novel or known functions of sex hormone receptorsand related molecules.

FOXA1 --- COBRA1 --- n/a --- estrogen --- progesterone receptor negative --- mutational profiling --- heterogeneous nuclear ribonucleoprotein K --- estrogen receptor alpha --- salivary gland tumors --- castration-resistant prostate cancer --- ELK1 --- fibroblasts --- androgen receptor --- melanocytes --- drug screening and proteomics --- PI3K pathway --- NELFB --- therapeutic targets --- immunohistochemistry --- androgen deprivation therapy --- ovarian cancer --- estrogen receptor --- epidermal growth factor receptor --- ethinylestradiol --- melanoma --- breast cancer --- keratinocytes --- G-protein coupled estrogen receptor --- prognosis --- levonorgestrel --- ultraviolet radiation --- sex hormone receptors --- upper urinary tract urothelial carcinoma --- CRPC --- nuclear factor erythroid 2-related factor 2 --- TP53

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The field of androgen excess disorders has advanced substantially since the original publication of this book. The Androgen Excess Society (AES) was founded to bring together investigators in the field. A better understanding of the screening, progression, and molecular genetics of nonclassic adrenal hyperplasia (NCAH) has improved the clinical care and diagnostic accuracy of these patients. New criteria for the diagnosis of the polycystic ovary syndrome (PCOS) were proposed in Rotterdam, criteria that have resulted in controversy and, hopefully, initiation of new studies. The association of insulin resistance with PCOS has been strengthened, and the role of metformin in tre- ing the infertility of the PCOS has been validated. Risks for diabetes and, more cont- versially, cardiovascular disease in women with PCOS have received substantial investigation. Our understanding of the epidemiology and economic impact of these disorders has expanded, emphasizing their critical importance. These are but a few highlights of how the terrain has changed in a relatively brief period of time. In keeping with these advances, the title of this book has been revised to reflect the growing importance of PCOS as the most prevalent androgen excess disorder in women, and arguably, as the one that might have the most serious adverse consequences for general health. There are fewer chapters to provide a more focused elucidation of the area. Several chapters were penned by new (and young) authors who are conducting cutting-edge research in the field.

Adrenal glands. --- Adrenal glands --- Androgens --- Polycystic ovary syndrome --- Adrenogenital Syndrome --- Adrenal Gland Diseases --- Ovarian Cysts --- Hormones --- 46, XX Disorders of Sex Development --- Disorders of Sex Development --- Ovarian Diseases --- Hormones, Hormone Substitutes, and Hormone Antagonists --- Cysts --- Endocrine System Diseases --- Adnexal Diseases --- Urogenital Abnormalities --- Gonadal Disorders --- Physiological Effects of Drugs --- Neoplasms --- Diseases --- Congenital Abnormalities --- Female Urogenital Diseases --- Pharmacologic Actions --- Male Urogenital Diseases --- Genital Diseases, Female --- Congenital, Hereditary, and Neonatal Diseases and Abnormalities --- Chemical Actions and Uses --- Female Urogenital Diseases and Pregnancy Complications --- Chemicals and Drugs --- Hyperandrogenism --- Polycystic Ovary Syndrome --- Adrenocortical Hyperfunction --- Medicine --- Health & Biological Sciences --- Clinical Endocrinology --- Gynecology & Obstetrics --- Metabolism --- Physiological effect --- Disorders, Congenital --- Congenital Disorders --- Neonatal Diseases and Abnormalities --- Congenital Disorder --- Disorder, Congenital --- Female Genital Diseases --- Gynecologic Diseases --- Diseases, Female Genital --- Diseases, Gynecologic --- Female Genital Disease --- Genital Disease, Female --- Gynecologic Disease --- Male Genitourinary Diseases --- Genitourinary Disease, Male --- Genitourinary Diseases, Male --- Male Genitourinary Disease --- Male Urogenital Disease --- Urogenital Disease, Male --- Urogenital Diseases, Male --- Chemical Actions --- Actions, Chemical --- Actions, Pharmacologic --- Female Genitourinary Diseases --- Female Genitourinary Disease --- Female Urogenital Disease --- Genitourinary Disease, Female --- Genitourinary Diseases, Female --- Urogenital Disease, Female --- Urogenital Diseases, Female --- Abnormalities, Congenital --- Defects, Congenital --- Birth Defects --- Congenital Defects --- Deformities --- Abnormality, Congenital --- Birth Defect --- Congenital Abnormality --- Congenital Defect --- Defect, Birth --- Defect, Congenital --- Defects, Birth --- Deformity --- Benign Neoplasms --- Malignancy --- Neoplasia --- Neoplasm --- Neoplasms, Benign --- Cancer --- Tumors --- Benign Neoplasm --- Cancers --- Malignancies --- Neoplasias --- Neoplasm, Benign --- Tumor --- Drug Effects on Physiology --- Drug Physiological Effects --- Effects, Drug Physiological --- Physiological Effects, Drug --- Disorder, Gonadal --- Disorders, Gonadal --- Gonadal Disorder --- Abnormalities, Urogenital --- Genitourinary Abnormalities --- Abnormalities, Genitourinary --- Abnormality, Genitourinary --- Abnormality, Urogenital --- Genitourinary Abnormality --- Urogenital Abnormality --- Urogenital System --- Adnexal Disease --- Disease, Adnexal --- Diseases, Adnexal --- Diseases of Endocrine System --- Endocrine Diseases --- Disease, Endocrine --- Disease, Endocrine System --- Diseases, Endocrine --- Diseases, Endocrine System --- Endocrine Disease --- Endocrine System Disease --- System Disease, Endocrine --- System Diseases, Endocrine --- Cyst --- Hormones, Substitutes, Antagonists --- Disease, Ovarian --- Diseases, Ovarian --- Ovarian Disease --- Ambiguous Genitalia --- Genital Ambiguity --- Hermaphroditism --- Intersex Conditions --- Intersexuality --- Pseudohermaphroditism --- Sexual Development Disorders --- Sexual Differentiation Disorders --- Disorders of Sexual Development --- Sex Development Disorders --- Sex Differentiation Disorders --- Ambiguities, Genital --- Ambiguity, Genital --- Condition, Intersex --- Conditions, Intersex --- Differentiation Disorder, Sex --- Differentiation Disorder, Sexual --- Differentiation Disorders, Sex --- Differentiation Disorders, Sexual --- Disorder, Sex Differentiation --- Disorder, Sexual Differentiation --- Disorders, Sex Differentiation --- Disorders, Sexual Differentiation --- Genital Ambiguities --- Genitalia, Ambiguous --- Intersex Condition --- Intersexualities --- Sex Development Disorder --- Sex Differentiation Disorder --- Sexual Development Disorder --- Sexual Differentiation Disorder --- Hormone --- Hormone Receptor Agonists --- Agonists, Hormone Receptor --- Receptor Agonists, Hormone --- Corpus Luteum Cyst --- Corpus Luteum Cysts --- Cyst, Corpus Luteum --- Cyst, Ovarian --- Cysts, Corpus Luteum --- Cysts, Ovarian --- Ovarian Cyst --- Adrenal Gland Disease --- Disease, Adrenal Gland --- Diseases, Adrenal Gland --- Gland Disease, Adrenal --- Gland Diseases, Adrenal --- PCOD (Gynecology) --- PCOS (Gynecology) --- Polycystic ovarian disease --- Polyfollicular ovarian disease --- Sclerocystic ovarian degeneration --- Sclerocystic ovaries --- Sclerocystic ovary syndrome --- Stein-Leventhal syndrome --- Androgenic hormones --- Adrenal Gland Hyperfunction --- Hyperadrenalism --- Hyperadrenocorticism --- Hypercorticism --- Hyperfunction, Adrenal Gland --- Hyperfunction, Adrenocortical --- Androgen Effect --- Androgen Effects --- Androgen Receptor Agonists --- Androgenic Agents --- Androgenic Compounds --- Agents, Androgenic --- Agonists, Androgen Receptor --- Compounds, Androgenic --- Effect, Androgen --- Effects, Androgen --- Receptor Agonists, Androgen --- Receptors, Androgen --- Polycystic Ovarian Syndrome --- Polycystic Ovary Syndrome 1 --- Sclerocystic Ovarian Degeneration --- Sclerocystic Ovaries --- Sclerocystic Ovary Syndrome --- Stein-Leventhal Syndrome --- Ovarian Degeneration, Sclerocystic --- Ovarian Syndrome, Polycystic --- Ovary Syndrome, Polycystic --- Ovary, Sclerocystic --- Sclerocystic Ovary --- Stein Leventhal Syndrome --- Syndrome, Polycystic Ovary --- Syndrome, Stein-Leventhal --- abnormalities --- agonists --- 46, XX DSD --- 46,XX DSD --- 46,XX Disorders of Sex Development --- Female Pseudohermaphroditism --- Female Pseudohermaphroditisms --- Pseudohermaphroditism, Female --- Pseudohermaphroditisms, Female --- Adrenogenital Syndromes --- Syndrome, Adrenogenital --- Syndromes, Adrenogenital --- Medicine. --- Endocrinology. --- Medicine & Public Health. --- Internal medicine --- Endocrinology .