Endocrine Abstracts

Gender or sex assignment is instantaneous at birth in the vast majority of infants. Rarely, the external genitalia are sufficiently ambiguous to render an assignment impossible and genetic, hormonal and radiological investigations are necessary before a decision can be reached about the sex of rearing. The commonest cause of such ambiguous genitalia is adrenal 21-hydroxylase deficiency (congenital adrenal hyperplasia) leading to virilisation of an affected female newborn. The XY infant with under-masculinisation represents a challenge of diagnosis due to numerous possible causes. A simple classification refers to disorders of testis formation (gonadal dysgenesis), defects in androgen biosynthesis (for example, LH receptor dysfunction or 17beta-hydroxysteroid dehydrogenase deficiency) and resistance to the action of androgens (the androgen insensitivity syndromes). A number of syndromes also comprise genital anomalies as a contributory component. Less severe genital anomalies which do not give rise to questions about birth gender such as hypospadias, micropenis and undescended testes are more common. Indeed, it has been suggested that deviation of the genital anatomy from the 'ideal' male or female newborn occurs in as many as two per cent of live births. The evidence that environmental factors may have a role in developmental genital anomalies is less persuasive in humans than in animals. However, variations in the incidence of undescended testes and hypospadias within populations raise the possibility of gene-environment interactions which need to be assessed by combined laboratory and epidemiological studies. A multi-centre EU-funded study has addressed the question and preliminary results do indicate that undescended testes, at least, may be increasing in frequency perhaps as a result of environmental factors.