Bone Mineral Density in Women Living with Complete Androgen Insensitivity Syndrome and Intact Testes or Removed Gonads

Abstract

Complete androgen insensitivity syndrome (CAIS) is due to complete androgen resistance in androgen-dependent tissues. Since androgens are involved in growth, development, and mass maintenance of the skeleton, bone health may be a relevant clinical issue for improving quality of life of women living with CAIS. Bone mineral density (BMD) in women with CAIS and intact gonads has been reported in a normal range, although exceptions are known showing a low BMD mainly at the lumbar level. In women with CAIS and removed gonads, BMD is usually reduced at both the lumbar spine and femoral neck. However, the fracture risk remains largely unknown. In women with CAIS, hormonal replacement therapy may improve BMD, but it does not normalize it. Several factors may be operative (e.g., loss of AR signaling at the bone level, gonadal removal, and age at surgery [before or after attainment of the peak bone mass], inadequate sex steroid replacement therapy, poor compliance with hormonal treatment, high serum FSH levels, lack of testicular protein hormones after gonadal removal), but they are poorly evaluated. In conclusion, the maintenance of testes may represent a strategy to improve bone health in women with CAIS, but a strict follow-up to monitor the cancer risk is mandatory mainly from their 20s onwards. Optimal sex steroid substitutive therapy in adolescence and adulthood is a key factor to improve BMD status in women with CAIS and removed gonads, but conclusive data on optimal management are lacking.