Androgen insensitivity syndrome

Androgen insensitivity syndrome (AIS), also known as testicular feminization syndrome, is a rare genetic condition in which an individual with a 46,XY karyotype (genetically male) has partial or complete inability to respond to androgens (male sex hormones such as testosterone). The condition is caused by pathogenic variants in the AR gene, which encodes the androgen receptor. Because the body's cells cannot respond appropriately to androgens, the development of male internal and external genitalia is impaired to varying degrees, despite the presence of functional testes that produce normal or elevated levels of testosterone. AIS exists on a clinical spectrum. Complete androgen insensitivity syndrome (CAIS) presents with typical female external genitalia, absent or rudimentary Müllerian structures (uterus and fallopian tubes), a blind-ending vagina, undescended testes, and female breast development at puberty. Affected individuals are typically raised as females and often present in adolescence with primary amenorrhea. Partial androgen insensitivity syndrome (PAIS) presents with ambiguous genitalia ranging from predominantly female to predominantly male phenotypes, and mild androgen insensitivity syndrome (MAIS) may present with male genitalia, gynecomastia, and/or infertility. Management of AIS is multidisciplinary and individualized. For individuals with CAIS, gonadectomy (removal of undescended testes) may be recommended due to a small but real risk of gonadal malignancy, though timing is debated — many clinicians now recommend delaying gonadectomy until after puberty to allow natural feminization. Hormone replacement therapy with estrogen is typically initiated after gonadectomy. Vaginal dilation or surgical vaginoplasty may be offered if needed. For PAIS, management decisions regarding sex of rearing, surgical interventions, and hormonal therapy are complex and require careful consideration by a team including endocrinologists, surgeons, psychologists, and the patient and family. Psychological support is an essential component of care for all individuals with AIS.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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