What is the management plan for androgen insensitivity syndrome (AIS)?

Management of Androgen Insensitivity Syndrome (AIS)

The management of Androgen Insensitivity Syndrome requires a multidisciplinary approach focusing on gonadectomy, hormone replacement therapy, psychological support, and genetic counseling to optimize quality of life and prevent long-term health complications. 1, 2

Diagnosis and Initial Assessment

• AIS is characterized by peripheral androgen resistance due to androgen receptor mutations in individuals with 46,XY karyotype, resulting in a female phenotype despite male genetics 3
• Clinical presentation varies based on the degree of androgen insensitivity:
  • Complete AIS (CAIS): Female external genitalia, primary amenorrhea, absent uterus and ovaries 3
  • Partial AIS (PAIS): Variable degrees of genital ambiguity 3
  • Mild AIS (MAIS): Male phenotype with infertility or gynecomastia 2
• Diagnostic workup should include:
  • Karyotype analysis to confirm 46,XY chromosomal pattern 4
  • Hormonal profile (elevated testosterone and LH levels despite female phenotype) 3
  • Genetic testing for androgen receptor mutations 2
  • Imaging studies (MRI/ultrasound) to evaluate internal reproductive structures 4

Surgical Management

• Gonadectomy is recommended due to the increased risk of gonadal malignancy 4
  • Risk increases with age: 3.6% at age 25 and up to 33% at age 50 4
  • Timing considerations:
    • Traditionally performed after puberty to allow natural feminization 5
    • Delayed gonadectomy requires careful monitoring 5
• Vaginoplasty may be considered in cases with vaginal hypoplasia, based on patient preference and readiness 3

Hormone Replacement Therapy (HRT)

• Estrogen replacement therapy should be initiated after gonadectomy or at puberty if gonadectomy was performed earlier 1, 5
• HRT goals include:
  • Promoting development of secondary sexual characteristics 3
  • Maintaining bone health and preventing osteoporosis 1
  • Supporting cardiovascular health 3
• Estrogen formulations and dosing should be tailored based on age and clinical response 5
• Long-term monitoring of bone mineral density is essential 1

Psychological Support and Counseling

• Gender identity counseling should be provided, recognizing that most individuals with CAIS identify as female 3
• Psychological support addressing:
  • Body image concerns 2
  • Fertility issues and reproductive options 2
  • Disclosure of diagnosis to the patient and family 3
• Regular psychological assessment to monitor adjustment and quality of life 4

Genetic Counseling

• Family screening should be offered to identify female carriers 2
• Genetic counseling regarding:
  • X-linked recessive inheritance pattern 4
  • Reproductive options for family planning 2
  • Prenatal diagnosis possibilities for future pregnancies 3

Long-term Follow-up

• Regular monitoring of:
  • Hormone replacement adequacy 1
  • Bone health with periodic bone density scans 1
  • Psychological well-being 4
• Annual clinical evaluations to assess overall health and treatment response 3

Special Considerations

• Fertility options should be discussed, including adoption and assisted reproductive technologies 2
• Vaginal dilation may be recommended for those with vaginal hypoplasia 3
• Transition of care from pediatric to adult services should be carefully planned 2

The management of AIS requires ongoing collaboration between endocrinologists, gynecologists, urologists, geneticists, and mental health professionals to provide comprehensive care and optimize quality of life 4.