Disorders of androgen action.

Area of Science:

• Endocrinology
• Genetics
• Reproductive Medicine

Background:

• Disorders of androgen action are primary causes of male pseudohermaphroditism.
• Key conditions include 5-alpha reductase (5α-R) deficiency and androgen receptor defects.

Purpose of the Study:

• To outline the clinical presentations, diagnostic approaches, and management strategies for male pseudohermaphroditism caused by androgen action disorders.
• To differentiate between 5α-R deficiency and androgen insensitivity syndromes.

Main Methods:

• Clinical phenotyping and biochemical testing (hormone levels, hormone ratios post-hCG stimulation).
• Genetic analysis to identify mutations in the 5α-R-2 and androgen receptor genes.
• Assessment of androgen-binding capacity in fibroblasts.

Main Results:

• 5α-R deficiency presents with female genitalia and some masculinization, with diagnosis aided by elevated testosterone/dihydrotestosterone ratios and genetic mutation identification.
• Androgen receptor defects include complete (CAIS) and partial (PAIS) insensitivity syndromes with distinct clinical features.
• CAIS typically presents at birth or puberty with a female phenotype, while PAIS shows a spectrum of undervirilization.

Conclusions:

• Accurate diagnosis of male pseudohermaphroditism requires integrated clinical, biochemical, and genetic evaluation.
• Management strategies vary based on the specific disorder, patient age, and genetic findings.
• Psychological support and appropriate timing of interventions like gonadectomy are crucial for patient well-being.