Complete Androgen Insensitivity Syndrome has an estimated prevalence between 2/100,000 and 5/100,000.

CAIS is caused by mutations in the AR gene on the X chromosome and is inherited in an X-linked recessive manner (see RareShare Guide on Genetic Inheritance). Over 500 different AR mutations have been identified in patients with androgen insensitivity syndrome. 80-100% of CAIS patients have an AR mutation compared to around 16% for partial androgen insensitivity syndrome.The mutation results in the body's cells being completely unable to respond to androgens (male hormones) like testosterone. Androgens like testosterone and dihydrotestosterone are responsible for primary sex characteristics, involving the masculinization of genitals during fetal development, and appearance of secondary sex characteristics like facial hair during puberty. Complete androgen resistance interferes with both processes.

• Female external genitalia at birth

• Absent or sparse pubic and axillary (armpit) hair

• Breast development during puberty

• Absent menstruation (primary amenorrhea)

• Shallow or absent vagina

• Absence of uterus and fallopian tubes

• Undescended or absent testes (may be in the abdomen or pelvis)

• Tall stature compared to average female height

• Lack of acne during puberty

• Reduced bone density (osteoporosis risk)

• Infertility

• Normal to high testosterone levels (but ineffective due to receptor insensitivity)

• Elevated estradiol levels (converted from testosterone)

• Clinical evaluation: absence of menstruation, absent/delayed puberty, external female genitalia, pelvic exam assessing vaginal depth, hernia or lumps in the groin (infants), family history

• Radiological imaging: ultrasound or MRI showing lack of female reproductive organs and locating undescended testes

• Blood tests: elevated testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH)

• Genetic testing: karyotype (chromosome study), sequence the AR gene

There is no cure for CAIS. Treatment generally focuses on managing symptoms and improving quality of life. This includes:

• Estrogen replacement therapy (after puberty)

• Vaginal dilation to lengthen cavity

• Vaginoplasty if desired

• Monitoring of or prophylactic removal of undescended testes (cancer risk)

• Regular bone density scans 

• Psychological support

• Genetic counseling for family members

The prognosis for individuals with CAIS is favorable with proper management and counseling. Patients have a normal life expectancy and can live active fulfilling lives. The main complications are osteoporosis, mental health burden, sexual dysfunction, infertility, and cancer. Testicular monitoring and or removal helps reduce the risk of cancer. Meanwhile regular bone scans, hormonal therapy, and calcium/vitamin D supplements can reduce the risk of osteoporosis. Counseling can help address issues of gender identity, body image, and sexual functioning. Assisted reproductive technologies may help those wishing to bear children.

Androgen Insensitivity Syndrome: Complete & Partial. (2021, December 14). Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/22199-androgen-insensitivity-syndrome

Fulare, S., Deshmukh, S., & Gupta, J. (2020). Androgen Insensitivity Syndrome: A rare genetic disorder. International Journal of Surgery Case Reports, 71, 371–373. https://doi.org/10.1016/j.ijscr.2020.01.032

Känsäkoski, J., Jääskeläinen, J., Jääskeläinen, T., Tommiska, J., Saarinen, L., Lehtonen, R., Hautaniemi, S., Frilander, M. J., Palvimo, J. J., Toppari, J., & Raivio, T. (2016). Complete androgen insensitivity syndrome caused by a deep intronic pseudoexon-activating mutation in the androgen receptor gene. Scientific Reports, 6(1), 32819. https://doi.org/10.1038/srep32819