From the Guidelines
For individuals with partial androgen insensitivity syndrome (PAIS), a multidisciplinary approach to management is crucial, with treatment depending on gender assignment, which should be determined based on the degree of genital virilization, potential for sexual function, and family preferences, as noted in the Chicago Consensus statement 1. When managing PAIS, several key factors must be considered, including:
- The degree of genital virilization
- Potential for sexual function
- Family preferences
- The need for surgical interventions, such as hypospadias repair or removal of undescended testes to prevent malignancy
- The potential need for hormone replacement therapy, such as testosterone supplementation for those raised as males, typically starting at 50-100mg monthly and adjusted based on response, or estrogen replacement therapy for those raised as females, starting at puberty with low doses of 0.25-0.5mg daily and gradually increasing 1. It is essential to prioritize a multidisciplinary approach, involving endocrinologists, urologists, psychologists, and geneticists, to address the complex needs of individuals with PAIS, including psychological support throughout development to address gender identity and body image concerns, as the development of gender dysphoria is a significant concern, with up to 25% of individuals with PAIS experiencing signs of gender dysphoria over time 1. The management of PAIS should be highly individualized, taking into account the unique needs and circumstances of each patient, with a focus on optimizing quality of life, minimizing morbidity, and reducing mortality, as the evidence supporting specific gender assignment is weak for most forms of DSD due to heterogeneous/ inadequate sample size, limited followup, and inability to contact individuals after puberty 1.
From the Research
Definition and Causes of Partial Androgen Insensitivity Syndrome
- Partial androgen insensitivity syndrome (PAIS) is a disorder characterized by peripheral androgen resistance due to androgen receptor mutations in subjects with 46 XY karyotype 2.
- The severity of hormone resistance determines the wide spectrum of phenotypes, with PAIS being one of the phenotypes 2, 3.
- PAIS is caused by mutations in the androgen receptor, resulting in resistance to the physiologic activities of androgens 4.
Clinical Presentation and Diagnosis
- Clinical suspicion of PAIS can arise at birth due to the presence of variable degrees of ambiguity of the external genitalia 2.
- Laboratory tests showing elevated LH and testosterone levels despite mild or absent virilization may be helpful in diagnosis 2, 3.
- Diagnosis can be achieved only after genetic testing (karyotype examination and androgen receptor sequencing) 2.
- A novel mutation in the androgen receptor can also be identified through molecular and genetic studies 5.
Management and Treatment
- Management of PAIS depends on the phenotype and social sex of the individual 3.
- A multidisciplinary team consisting of physicians, surgeons, and psychologists is highly recommended to support the patient and his/her family on gender identity choices and subsequent appropriate therapeutic decisions 2, 6, 4.
- Hormone replacement therapy is needed following gonadectomy 6.
- Patients who choose to retain the gonads are at risk of developing germ cell tumors 6.