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Management of disorders of sex development

Key Points

  • Disorders of sex development (DSDs) include at least 50 different congenital abnormalities of urogenital differentiation

  • The terms 'variations of sex development' and 'differences of sex development' can also be used to describe individuals with DSDs

  • Diagnosis of DSDs requires clinical assessment, morphological determination, endocrine evaluation and genetic studies; however, the pathogenetic mechanisms have only been elucidated in a subset of individuals with DSDs

  • Management of patients with DSDs should involve a group of specialists working in an interdisciplinary team in a dedicated Centre of Expertise

  • Important areas of DSD research include personalized approaches to patient management and the development of diagnostic strategies that combine modern genetic techniques with endocrine evaluations

Abstract

The medical term disorders of sex development (DSDs) is used to describe individuals with an atypical composition of chromosomal, gonadal and phenotypic sex, which leads to differences in the development of the urogenital tract and reproductive system. A variety of genetic factors have been identified that affect sex development during gonadal differentiation or in specific disorders associated with altered androgen biosynthesis or action. The diagnosis of DSDs in individuals and the subsequent management of patients and their families requires a targeted and structured approach, involving a multidisciplinary team with effective communication between the disciplines. This approach includes distinct clinical, imaging, laboratory and genetic evaluations of patients with DSDs. Although treatment of patients with DSDs can include endocrine and surgical options, many patients have concerns that arise from past incorrect treatments that were founded on the traditional binary concept of the sexes. To dispel these concerns, it is necessary to create centres of expertise for DSDs that include physicians, surgeons, psychologists and specialists in diagnostic procedures to manage patients and their families. Additionally, the inclusion of trained peer support in the multidisciplinary DSD team seems to be integral to the supportive management of patients with DSDs. Most importantly, dealing with DSDs requires acceptance of the fact that deviation from the traditional definitions of gender is not necessarily pathologic.

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Figure 1: Composition of a team managing patients with disorders of sex development.
Figure 2: Evaluation of disorders of sex development by clinical, laboratory and genetic investigations.

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Acknowledgements

The authors would like to acknowledge the support of the European Science Foundation (COST Action BM1303).

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O.H., W.B., L.M., L.W., R.W., T.S. and P.-M.H. researched data for the article. O.H., W.B., L.M., L.W., R.W., U.D. and P.-M.H. made substantial contributions to discussions of the content. O.H., W.B., L.W., R.W. and P.-M.H. wrote the article. O.H., W.B., L.M., L.W., R.W., T.S., U.D. and P.-M.H. reviewed and/or edited the manuscript before submission.

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Correspondence to Olaf Hiort.

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Hiort, O., Birnbaum, W., Marshall, L. et al. Management of disorders of sex development. Nat Rev Endocrinol 10, 520–529 (2014). https://doi.org/10.1038/nrendo.2014.108

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