Surgery in disorders of sex development (DSD) with a gender issue: If (why), when, and how?

The birth of an intersex child prompts a long-term management strategy that involves a myriad of professionals working with the family. There has been progress in diagnosis, surgical techniques, understanding psychosocial issues and in recognizing and accepting the place of patient advocacy. The Lawson Wilkins Paediatric Endocrine Society (LWPES) and the European Society for Paediatric Endocrinology (ESPE) considered it timely to review the management of intersex disorders from a broad perspective, to review data on longer term outcome and to formulate proposals for future studies. The methodology comprised establishing a number of working groups whose membership was drawn from 50 international experts in the field. The groups prepared prior written responses to a defined set of questions resulting from an evidence based review of the literature. At a subsequent gathering of participants, a framework for a consensus document was agreed. This paper constitutes its final form.

The risk for the development of germ cell tumors is an important factor to deal with in the management of patients with disorders of sex development (DSD). However, this risk is often hard to predict. Recently, major progress has been made in identifying gene-products related to germ cell tumor development (testis-specific protein-Y encoded and octamer binding transcription factor 3/4) and in recognizing early changes of germ cells (maturation delay, preneoplastic lesions, and in situ neoplasia). The newly recognized "undifferentiated gonadal tissue" has been identified as a gonadal differentiation pattern bearing a high risk for the development of gonadoblastoma. It is expected that the combination of these findings will allow for estimation of the risk for tumor development in the individual patient (high risk/intermediate risk/low risk). This article reviews the recent literature regarding the prevalence of germ cell tumors in patients with DSD. Some major limitations regarding this topic, including a confusing terminology referring to the different forms of intersex disorders and unclear criteria for the diagnosis of malignant germ cells at an early age (maturation delay vs. early steps in malignant transformation) are discussed. Thereafter, an overview of the recent advances that have been made in our knowledge of germ cell tumor development and the correct diagnosis of early neoplastic lesions in this patient population is provided. A new classification system for patients with DSD is proposed as a tool to refine our insight in the prevalence of germ cell tumors in specific diagnostic groups.

Individuals with 5alpha-reductase-2 deficiency (5alpha-RD-2) and 17beta-hydroxysteroid dehydrogenase-3 deficiency (17beta-HSD-3) are often raised as girls. Over the past number of years, this policy has been challenged because many individuals with these conditions develop a male gender identity and make a gender role change after puberty. The findings also raised doubts regarding the hypothesis that children are psychosexually neutral at birth and emphasized the potential role of prenatal brain exposure to androgens in gender development. If prenatal exposure to androgens is a major contributor to gender identity development, one would expect that all, or nearly all, affected individuals, even when raised as girls, would develop a male gender identity and make a gender role switch later in life. However, an estimation of the prevalence of gender role changes, based on the current literature, shows that gender role changes occur frequently, but not invariably. Gender role changes were reported in 56-63% of cases with 5alpha-RD-2 and 39-64% of cases with 17beta-HSD-3 who were raised as girls. The changes were usually made in adolescence and early adulthood. In these two syndromes, the degree of external genital masculinization at birth does not seem to be related to gender role changes in a systematic way.