46,XY disorders of sex development – the undermasculinised male with disorders of androgen action

Insensitivity to the action of androgens is a common cause of undermasculinisation in 46,XY individuals. These disorders are a result of the failure of major androgens to act via the intracellular androgen receptor and, thus, the genomic effects of androgen signalling are disrupted. The phenotype of affected individuals can vary considerably, depending on the dysfunction of the receptor. In childhood, the diagnosis is often complicated due to the lack of sensitive biochemical determinants, whilst during adolescence and in adults, the diagnosis can be readily made because of the striking clinical feminisation and a conclusive laboratory analysis. A variety of mutations in the androgen receptor have been analysed, providing insight into the complex pathways of intracellular processing and signal transduction via the androgen receptor. Endocrine therapy in androgen-insensitivity syndrome is controversial, because till date the special hormonal profiles in androgen insensitivity have not been acknowledged in replacement strategies.

Keywords: androgen insensitivity, androgen receptor, cofactors, dihydrotestosterone, genetics, mutations, testosterone

Abbreviations: CAIS, complete androgen insensitivity syndrome, PAIS, partial androgen insensitivity syndrome, MAIS, minimal androgen insensitivity syndrome, AR, androgen receptor