Long-term consequences of androgen insensitivity syndrome

Androgen insensitivity syndrome (AIS) is one of the most common sexual developmental disorders. According to the grade of the remaining androgen receptor (AR) function, AIS is classified as complete (CAIS), partial (PAIS) or mild (MAIS). In CAIS, the prevalence of germ cell tumours is increased compared with the general population. Although patients with CAIS used to undergo gonadectomy before puberty, nowadays a gonadectomy is recommended after spontaneous puberty, and up to 15% of patients retain their gonads. Nevertheless, the risk of germ cell tumour increases gradually after puberty. Annual follow-up with ultrasound or magnetic resonance imaging (MRI) is recommended. Unfortunately, these imaging methods are not sensitive enough for the diagnosis of an in situ germ cell tumour. In PAIS, the risk of germ cell tumour is higher than in CAIS; therefore, an early gonadectomy or an orchidopexy is indicated. Optimal hormone replacement therapy (HRT) is necessary for long-term health. The risks of osteopenia and of regimen osteoporosis are higher, ESPECIALLY in patients with early gonadectomy. Infertility is the rule in CAIS and PAIS. A few mutations do not affect fertility detrimentally, and these are responsible for MAIS. In PAIS leading to a predominantly male phenotype or ambiguous genitalia, multiple surgical procedures for gynaecomastia and/or hypospadias are required. Some small studies have found a higher risk of obesity, hyperlipidaemia and impaired insulin sensitivity. Psychological support is essential, as the prevalence of psychiatric disorders is increased. In conclusion, the diagnosis of AIS has long-term consequences for which shared decision-making (physicians, patients, parents) is appropriate.