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In this perspective article we discuss the limitations of sex as a binary concept and how it is challenged by medical developments and a better understanding of gender diversity. Recent data indicate that sex is not a simple binary classification based solely on genitalia at birth or reproductive capacity but encompasses various biological characteristics such as chromosomes, hormones, and secondary sexual characteristics. The existence of individuals with differences in sex development (DSD) who do not fit typical male or female categories further demonstrates the complexity of sex. We argue that the belief that sex is strictly binary based on gametes is insufficient, as there are multiple levels of sex beyond reproductivity. We also explore the role of sex in sex determination, gene expression, brain development, and behavioural patterns and emphasize the importance of recognizing sex diversity in personalized medicine, as sex can influence disease presentation, drug response, and treatment effectiveness. Finally, we call for an inter- and transdisciplinary approach to study sex diversity and develop new categories and methodologies that go beyond a binary model., (© 2023 the author(s), published by De Gruyter.)

Much later than the discovery of "sex chromosomes" and of "sex hormones", genetics started delivering detailed explanations of sex-determining developmental pathways. Despite increasing knowledge of biological processes, concepts and theories about sex development are never based on facts alone. There are inevitable entanglements of biological description and changing cultural assumptions and they play a key role in how sex genes are framed and interpreted in biological research. In this review article we first focus on the early 20th century biology that worked in a hormone-based paradigm. Genetic explanations emerged later, first on the basis of sex chromosomes; starting in the 1980s, on the basis of genes. We highlight orthodox views of female development, which saw the default pathway of human sex development. We will show how recent findings in biology challenge it. The article discusses the interactions of causal claims in science with cultural assumption about gender and outlines three influential strands of critical feminist philosophy of science: the critique of genetic determinism and genetic essentialism, of dualist assumptions, and of an androcentric bias in the conception of research strategies. In the final section we suggest key agenda points of future genetic research on sex determination., (© 2023 the author(s), published by De Gruyter.)