Height and bone mineral density in androgen insensitivity syndrome with mutations in the androgen receptor gene

  title={Height and bone mineral density in androgen insensitivity syndrome with mutations in the androgen receptor gene},
  author={D. L. S. Danilovic and Pedro Henrique Silveira Corr{\^e}a and Elaine M. F. Costa and K F Melo and B. B. Mendonça and Ivo JP Arnhold},
  journal={Osteoporosis International},
Introduction and hypothesisAndrogen insensitivity syndrome (AIS) constitutes a natural model to study effects of androgens and estrogens on growth and bone density. We evaluated height and bone density in patients with AIS with mutations in the androgen receptor (AR) gene.MethodsA retrospective analysis was conducted of eight subjects with complete AIS (CAIS) and four with partial AIS (PAIS) submitted to gonadectomy followed by estrogen replacement, and three with PAIS who did not undergo… 

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

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.

Case Report: Low Bone and Normal Lean Mass in Adolescents With Complete Androgen Insensitivity Syndrome

These limited data indicate that adolescents with CAIS have bone mass deficit, and further studies are needed to understand the extent of BMD abnormalities and the effect of gonadectomy, especially early in childhood, and to establish the optimal HRT regimen for bone accrual.

Bone mass in subjects with Klinefelter syndrome: role of testosterone levels and androgen receptor gene CAG polymorphism.

Testosterone levels and AR CAG polymorphism are not associated with bone mass phenotype in KS, and no significant relationship was observed between testosterone levels and bone parameters.

Comparison of bone mineral density and body proportions between women with complete androgen insensitivity syndrome and women with gonadal dysgenesis.

Taller stature in late gonadectomised CAIS women suggests an oestrogen deficiency in these women prior to gonadectomy, and increased lower to upper body ratio in GD(XY) women compared with the other groups implies that these subjects have the greatest degree of oestrogens deficiency in puberty.

Bone mineral density, body composition and metabolic profiles in adult women with complete androgen insensitivity syndrome and removed gonads using oral or transdermal estrogens.

The results reinforce the importance of adequate hormonal treatment in women living with CAIS, suggesting a better effect from the transdermal route over the oral route.

Male patients with partial androgen insensitivity syndrome: a longitudinal follow-up of growth, reproductive hormones and the development of gynaecomastia

Gynaecomastia and impaired phallic growth are frequently observed in adults with PAIS, but may be ameliorated by androgen therapy, and the authors suggest that male patients presenting with gynaecOMastia in puberty and elevated circulating levels of testosterone, estradiol and LH in puberty, but normal FSH, should be suspected of having PAIS and undergo genetic testing for AR mutations.

Anthropometric, metabolic and bone changes in women with premature ovarian failure when using estradiol analogues

The preliminary data suggest that estradiol is administered both transdermally and orally in young women with hypergonadotropic amenorrhea, with a significant time-treatment interaction effect.

Complete Androgen Insensitivity Syndrome: From Bench to Bed

Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk).

Osteoporosis in Klinefelter's syndrome.

Possible new determinants for osteoporosis in KS might be related to the AR function and insulin-like factor 3 (INSL3) levels, which has an anabolic role on bone metabolism by acting on osteoblasts and INSL3 levels are low in KS.

The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene

Boys with genetically confirmed PAIS are likely to have a poorer clinical outcome than those with XY DSD, with normal T synthesis, and without an identifiable AR mutation.



Altered Bone Mineral Density in Patients with Complete Androgen Insensitivity Syndrome

Both aBMD and vBMD are reduced in cAIS patients, while bone turnover and the fracture risk seem not to be increased, indicating that both androgens and estrogens may be required for acquisition of bone density during childhood.

Changes in bone mineral density after orchidectomy and hormone replacement therapy in individuals with androgen insensitivity syndrome.

Results indicate that both oestrogen and androgen play an important role in balancing BMD in men and that androgen plays anImportant role in bone mineralization in 46,XY individuals.

The contribution of testosterone to skeletal development and maintenance: lessons from the androgen insensitivity syndrome.

It is concluded that even when compliance to exogenous estrogen use is excellent, women with complete AIS show moderate deficits in spine BMD, averaging close to 1 SD from normative means, and that with correction of BMD for bone size, skeletal deficits are magnified and include the proximal femur.

Bone mineral density in the complete androgen insensitivity and 5alpha-reductase-2 deficiency syndromes.

1) Androgens are of direct importance in the development and/or maintenance of BMD; and 2) testosterone and/ or low levels of dihydrotestosterone appear to be sufficient for BMD development and-or maintenance.

Bone mass in androgen-insensitivity syndrome: Response to hormonal replacement therapy

Bone mineral density (BMD) measured by dual X-ray absorptiometry in lumbar spine and proximal femur was sharply reduced at the initial visit, and remained unchanged during long-term follow-up on hormone replacement therapy with estrogens and progestin.

Clinical, hormonal, behavioral, and genetic characteristics of androgen insensitivity syndrome in a Brazilian cohort: five novel mutations in the androgen receptor gene.

All subjects with PAIS maintained at postpubertal age the gender identity and social sex that was assigned to them in infancy, in contrast to other forms of pseudohermaphroditism.

Pubertal growth in patients with androgen insensitivity: indirect evidence for the importance of estrogens in pubertal growth of girls.

It is concluded that in normal girls, the pubertal growth spurt also results from the action of estrogens rather than of adrenal androgens, and physiologic estrogen replacement in hypogonadal females should be started at a bone age of about 11 years, and should not be delayed in the hope of achieving a greater mature height.

Estrogen, Bone, Growth and Sex: A Sea Change in Conventional Wisdom

  • M. Grumbach
  • Biology, Medicine
    Journal of pediatric endocrinology & metabolism : JPEM
  • 2000
Establishing a role for estrogen does not exclude a direct action of testosterone on bone in the human male (especially on cortical bone), but this action is less characterized than thought in the past and is relatively minor in comparison with the major effect of estrogen in the male.

Cross genotype sex hormone treatment in two cases of hypogonadal osteoporosis.

Phenotypically-matched sex hormone therapy in patients with abnormal sexual differentiation is essential not only to maintain external appearance but also for the preservation of bone mass.