Awarded with the 2018 Prose Award in Clinical Medicine, the third edition of Principles of Gender-Specific Medicine explored and described exciting new areas in biomedicine that integrated technology into the treatment of disease and the augmentation of human function. Novel topics such as the sex-specific aspects of space medicine, the development and the use of genderized robots and a discussion of cyborgs were included in the third edition, providing a preview of the expanding world of sex-specific physiology and therapeutics. This Fourth Edition is a continuation of the mission to trace the relevance of biological sex to normal function and to the experience of disease in humans.We are now twenty years into the postgenomic era. The investigation of how the genome produces the phenome has led to fascinating insights as well as yet unanswered questions. Principles of Gender-Specific Medicine, Fourth Edition, has a central theme: discuss advances in understanding the role of epigenetics in regulating gene expression in a dynamic, sex-specific way during human life. It explores the protean role of epigenetics in human physiology, the relevance of environmental experience to human function, the therapeutic promise of cutting-edge methodologies like gene manipulation, the preparation of humans for space travel, the use of artificial intelligence in detection and therapeutic decisions concerning disease states, the possibilities for technological support of not only compromised individuals but of the augmentation of human function, and an analysis of the benefits, limitations and issues that surround our current expectations of personalized medicine.

DedicationMarianne J. LegatoForewordMarek GlezermanPrefaceMarianne J. LegatoSection A1. Is there a role for Natural Selection in Sex Differences?Adriana Maggi2. Battle of the Sexes: How the Selection of Spermatozoa in the Female Reproductive Tract Manipulates the Sex Ratio of OffspringAlireza Fazeli, William Vincent Holt, Suranga Kodithuwakku, Kasun Godakumara and Lisa M. Thurston3. Gender/sex: Shaping identity in infancy and early childhood Anne Sterling and Jihyun Sung4. A gendered brain perspective from structure to brain network interactionsCarme Uribe, Leire Zubiaurre-Elorza and Antonio Guillamon5. Third Edition: Sex-specific implications of adverse intrauterine environment. Writing with Antonia Hufnagel.Catherine Aiken and Antonia Hufnagel6. Sex-Specific Brain Transcriptome of the MouseDiethard Tautz and Maryam Keshavarz7. Using the exposome to understand the role of the environment in gender- and sex-specific medicineGary W. Miller, Faith Anderson, Meghan Bucher, Yunjia Lai and Jocelyn Dicent8. Regulation of Gene Expression in the Brain by Sex HormonesJessica Tollkuhn and Simón(e) Sun9. Sex-specific disparities in mitochondrial function and its role in health and diseaseKeshav K. Singh and Suresh Mishra10. Sex Differences  in Fetal ProgrammingMarek Glezerman11. Sex Differences in the Brain: Focus on Developmental MechanismsMargaret M. McCarthy12. Genes, Environments and Epigenetic ModificationsMarla B. Sokolowski, Sydney Gram and Dustin J. Sokolowski13. Epigenetics: Mechanisms, Theory and Social ImplicationsMaurizio Meloni14. Adipose-derived Stem CellsSatoshi Sobajima, Yoshitomo Saita, Hideki Iwaguro, Ryosuke Kuroda and Masanori Tsubosaka15. Role of Sex Chromosomes in Human DiseaseNeil Bradbury16. Best-laid plans: The establishment of biological sex, and its susceptibility to disruptionPeter Koopman17. CRISPR Technology and Its Role in Treating Rare Imprinting DiseasesRadislav Sedlácek, Petr Nickl and Linn Amanda Syding18. Perinatal Genome and Brain Functions: The Case of Genomic ImprintingValter Tucci, Angelo Serani and Alice Melloni19. Microbiome: Impact of Gender on Function & Characteristics of Gut MicrobiomeVeena TanejaSection B20. Geoepidemiology and the Impact of Sex on Autoimmune DiseasesAna Lleo21. Molecular Mechanisms of Sex Differences in EpilepsySamba Reddy22. Consideration of biological sex in stem cell therapiesDan Gazit, Gadi Pelled, Zulma Gazit and Zoe Krut23. Sex and Human Brain Structure and Function: Moving Beyond the BinaryDaphna Joel24. Genomic and Epigenomic Signature at the branch-point among Genome, Phenome and Sexome in health and disease: A Multi-Omics approachDonato Gemmati and Veronica Tisato25. The Importance of Gender-Specific Medicine in the Pharmaceutical Industry, Clinical Practice, and Global Health CareIbis Sanchez-Serrano26. The neurobiology of gender identity and gender dysphoriaivanka SAVIC27. Biological Sex in the times of Precision NutritionJose M. Ordovas and D Corella28. The invaluable contribution of animal models in understanding sex-dependent differences in neuropsychiatric disordersLiana Fattore29. Sexual Dimorphism in Molecular Biology of CancerMehmet Tevfik Dorak30. The Importance of Expeditionary Fitness in Optimizing the  Human Commercial Spaceflight ExperienceMichael A. Schmidt31. Brain morphological changes associated with sexual orientationMikhail Votinov and Andrei A. Puiu32. Current options for the measurement and operationalization of sex and genderSabine Oertelt-Prigione33. Precision Medicine::  Overview and Challenges to Clinical ImplementationSusanne HagaSection C34. Assessment of fall risks in older females and males using an automated smartphone mobility suiteEmil Jovanov35. Impact of Statin Therapy on Sex HormonesAmirhossein Sahebkar, Zeljko Reiner, Hossein Chiti, Negin Parsamanesh and Tannaz Jamialahmadi36. The Role of Gender in Exercise Physiology and MetabolismAndreas M. Fritzen, Anne-Marie Lundsgaard and Bente Kiens37. Cerebral effects of gender affirming hormone treatments in transgender personsLeire Zubiaurre-Elorza, Antonio Guillamon and Carme Uribe38. Artificial Intelligence in HealthcareArthur Argenson and Virginia Devi-Chou39. Trauma and Gender in Primary CareDorte Mølgaard Christiansen40. Fertility Treatment and Preservation in Transgender Men and WomenDov Feldberg41. Sexual dimorphism of the pathophysiology and treatment of atrial fibrillationElaine Y. Wan, Ellie Coromilas, Stephanie Kochav and Jessica Hennessey42. Reductionistic and Holistic Research Approaches: Lessons from the COVID-19 PandemicFerric Fang and Arturo Casadevall43. Sex and Gender Differences in Sleep Disorders: An OverviewFidaa Shaib and Hrayr Attarian44. Estrogen: Impact on Cardiomyocytes and the HeartJin Kyung Kim45. Beyond Sex and Gender Differences: The Case for Women's Health ResearchLiisa Galea46. Dimorphic or bimodal? Measurement and Meaning of Sex/Gender from Bench to BedsideReubs J. Walsh47. Person Centred Cancer Genetic Counselling for Transgender and Gender Diverse PatientsJosephine Giblin48. Musculoskeletal Complaints in Male and Female Instrumental MusiciansRob G.H.H Nelissen and Laura Madelinde Kok49. Sex, Gender, and PainRoger Fillingim50. Urothelial Cancer: Bladder and Upper TractS. F. Shariat, Reza Sari Motlagh, Fajkovic Harun and Manuela Schmidinger51. Beyond the mask: the role of camouflaging in managing an autistic identity for girls and women Jan Burns and Siobhan Tierney52. Vulnerable Males and Strong Females: Gender Differences in Susceptibilty to Stress Factors during Prenatal Development from the Viewpoint of Life History TheorySylvia Kirchengast53. Robots and GenderTatsuya Nomura54. Sex Specificity in Neonatal OutcomesVineet Bhandari and Vishwanath Bhat55. Human Male and Female Phenotypes Depend on Lifestyles (Smoking and Hormonal Contraceptives): Implications for Prevention and CareIlaria Campesi and Flavia Franconi