The birth of an intersex child prompts a long term management strategy that involves a myriad of professionals working with the family. It is estimated that genital anomalies occur in 1 in 4500 births. There has been progress in diagnosis, surgical techniques, understanding psychosocial issues, and recognising and accepting the place of patient advocacy. The Lawson Wilkins Pediatric 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 several 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 published reports. At a subsequent gathering of participants, a framework for a consensus document was agreed. This paper constitutes its final form.
Advances in identification of molecular genetic causes of abnormal sex with heightened awareness of ethical issues and patient advocacy concerns necessitate a re‐examination of nomenclature.1
Terms such as intersex, pseudohermaphroditism, hermaphroditism, sex reversal, and gender based diagnostic labels are particularly controversial. These terms are perceived as potentially pejorative by patients,2
and can be confusing to practitioners and parents alike. The term “disorders of sex development” (DSD) is proposed, as defined by congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical.
The proposed changes in terminology are summarised in table 1. A modern lexicon is needed to integrate progress in molecular genetic aspects of sex development. As outcome data in individuals with DSD are limited, it is essential to employ precision when applying definitions and diagnostic labels.3,4
It is also appropriate to use terminology that is sensitive to the concerns of patients. The ideal nomenclature should be sufficiently flexible to incorporate new information yet robust enough to maintain a consistent framework. Terms should be descriptive and reflect genetic aetiology when available, and accommodate the spectrum of phenotypical variation. Clinicians and scientists must value its use and it must be understandable to patients and their families. An example of how the proposed nomenclature could be applied in a classification of DSD is shown in table 2.
Table 1Proposed revised nomenclature
Table 2An example of a DSD classification
Psychosexual development is traditionally conceptualised as three components. Gender identity refers to a person's self representation as male or female (with the caveat that some individuals may not identify exclusively with either). Gender role (sex‐typical behaviours) describes the psychological characteristics that are sexually dimorphic within the general population, such as toy preferences and physical aggression. Sexual orientation refers to the direction(s) of erotic interest (heterosexual, bisexual, homosexual) and includes behaviour, fantasies, and attractions. Psychosexual development is influenced by multiple factors such as exposure to androgens, sex chromosome genes, and brain structure, as well as social circumstance and family dynamics.
Gender dissatisfaction denotes unhappiness with assigned sex. Causes of gender dissatisfaction are poorly understood, even among individuals without DSD. Gender dissatisfaction occurs more frequently in individuals with DSD than in the general population, but is difficult to predict from karyotype, prenatal androgen exposure, degree of genital virilisation, or assigned gender.5,6,7
Prenatal androgen exposure is clearly associated with other aspects of psychosexual development.8,9
There are dose related effects on childhood play behaviour in girls with congenital adrenal hyperplasia (CAH), whereby those with the more severe mutations and marked genital virilisation play more with boys' toys.10
Prenatal androgen exposure is also associated with other psychological characteristics such as maternal interest and sexual orientation. It is important to emphasise the separability of sex‐typical behaviour, sexual orientation, and gender identity. Thus homosexual orientation (relative to sex of rearing) or strong cross‐sex interest in an individual with DSD is not
an indication of incorrect gender assignment. Understanding variations in psychosexual development in individuals with DSD requires reference to studies in non‐human species that show marked but complex effects of androgens on sex differentiation of the brain and on behaviour. Outcomes can be influenced by timing, dose, and type of androgen exposure, receptor availability, and modification by the social environment.11,12,13,14
Data from rodent studies suggest that sex chromosome genes may also influence brain structure and behaviour directly.15,16
However, studies in individuals with complete androgen insensitivity syndrome (CAIS) do not indicate a behavioural role for Y chromosome genes, although data are limited.17
Sex differences in brain structures have been identified across species, some of which coincide with pubertal onset, perhaps suggesting hormonal responsivity.18,19,20
The limbic system and hypothalamus, both playing a role in reproduction, show sex differences in specific nuclei but it is not clear when these differences emerge. Interpretation of sex differences is complicated by the effect of cell death and synaptic pruning on normal maturation and by effects of experience on the brain. Structure of the brain is not currently useful for gender assignment.