From the Guidelines
The management of Partial Androgen Insensitivity Syndrome (PAIS) requires a multidisciplinary approach involving endocrinologists, urologists, psychologists, and geneticists, with treatment decisions individualized based on the degree of androgen insensitivity, phenotypic presentation, and gender identity.
Key Considerations
- Treatment decisions should prioritize the individual's gender identity, phenotypic presentation, and degree of androgen insensitivity.
- For individuals raised as males, testosterone supplementation is typically initiated at puberty, starting with low doses (50-100 mg testosterone enanthate or cypionate intramuscularly every 3-4 weeks) and gradually increasing to adult replacement doses (200-250 mg every 2-3 weeks or daily transdermal applications of 5-10 g testosterone gel) 1.
- Surgical interventions may include hypospadias repair in childhood, orchiopexy for undescended testes, and gynecomastia correction during adolescence.
- For those raised as females, gonadectomy is recommended due to the risk of gonadal malignancy, followed by estrogen replacement therapy (starting with low-dose estradiol 0.5 mg daily, increasing gradually to 1-2 mg daily) at the time of expected puberty 1.
Psychological Support and Follow-up
- Psychological support is essential throughout development to address gender identity issues and body image concerns.
- Genetic counseling should be offered to affected individuals and their families to understand inheritance patterns and reproductive implications.
- Regular follow-up is necessary to monitor hormone levels, bone density, and overall health outcomes, as individuals with PAIS may have increased risks for metabolic disorders and osteoporosis.
Important Considerations for Treatment
- The Chicago Consensus statement did not include specific gender assignment recommendations for all diagnoses, but some consensus participants have provided separate, more specific recommendations 1.
- The possibility of dysphoria appears to be greater in certain forms of DSD, but the incidence is uncertain since a decision to proceed with gender reassignment is psychosocially complex and some individuals with dysphoria may not disclose or act on gender uncertainties 1.
From the Research
Definition and Management of Partial Androgen Insensitivity Syndrome (PAIS)
- Partial Androgen Insensitivity Syndrome (PAIS) is a form of disorders of sexual development, characterized by resistance of target tissues to the action of testosterone, leading to variable degrees of undervirilization in 46,XY individuals 2.
- The management and treatment of PAIS are not standardized and require individual evaluation and treatment, considering the risks and benefits of surgery, such as gonadectomy 3.
Treatment and Follow-up Protocols
- Treatment protocols for adults with PAIS are not well-established, and decisions on sex assignment, timing of gonadectomy, fertility, psychological outcomes, and genetic counseling are still open issues 2.
- A survey among healthcare professionals found that gonadectomy was recommended in early adulthood in 67% of centers for women with Complete Androgen Insensitivity Syndrome (CAIS), but the approach is more variable for PAIS, with 11% of centers recommending routine gonadectomy 4.
Gonadectomy in PAIS
- Gonadectomy is considered due to the increased risk of gonadal germ cell cancer (GGCC) associated with PAIS, but the timing and necessity of this procedure are still debated 4, 5.
- Some studies suggest that gonadectomy after puberty may be recommended, while others propose a biannual screening program for individuals who wish to keep their gonads, which needs to be evaluated in a prospective multi-center trial 5.
Multidisciplinary Management
- Multidisciplinary management, including psychiatric clinic referral, is essential for the diagnosis and treatment of PAIS, to address the complex physical and psychological aspects of the condition 6.
- Early diagnosis and individualized treatment approaches are crucial to improve the quality of life and outcomes for individuals with PAIS 6, 2.