Complete androgen insensitivity syndrome (CAIS) represents a main disorder of sex development. Women with CAIS may have their gonads removed before, during or after adolescence, thus requiring hormonal replacement therapy to induce puberty and/or maintain secondary sexual characteristics, to optimize bone mass accrual, and to promote physical and social well-being. Usually estrogens are used for this purpose, but formulations and doses should be better defined in multicentric prospective studies. Some women started testostosterone as hormonal replacement therapy, but this practice remains anecdotal. Bone health remains a crucial aspect in the management of persons with CAIS, but few sound data are available to guide clinical practice.

Keywords:
Complete androgen insensitivity syndrome, Adolescence, Hormonal replacement therapy, Estrogens, Testosterone, Bone health
1.
Ahmed SF, Rodie M, Jiang J, Sinnott RO: The European disorder of sex development registry: a virtual research environment. Sex Dev 2010;4:192–198.
2.
Hughes IA, Deeb A: Androgen resistance. Best Pract Res Clin Endocrinol Metab 2006;20:577–598.
3.
Audi L, Fernández-Cancio M, Carrascosa A, Andaluz P, Torán N, Piró C, Vilaró E, Vicens-Calvet E, Gussinyé M, Albisu MA, Yeste D, Clemente M, Hernández de la Calle I, Del Campo M, Vendrell T, Blanco A, Martínez-Mora J, Granada ML, Salinas I, Forn J, Calaf J, Angerri O, Martínez-Sopena MJ, Del Valle J, García E, Gracia-Bouthelier R, Lapunzina P, Mayayo E, Labarta JI, Lledó G, Sánchez Del Pozo J, Arroyo J, Pérez-Aytes A, Beneyto M, Segura A, Borrás V, Gabau E, Caimarí M, Rodríguez A, Martínez-Aedo MJ, Carrera M, Castaño L, Andrade M, Bermúdez de la Vega JA: Grupo de Apoyo al Síndrome de Insensibilidad a los Andrógenos (GrApSIA). Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development. J Clin Endocrinol Metab 2010;95:1876–1888.
4.
Melo KF, Mendonca BB, Billerbeck AE, Costa EM, Inácio M, Silva FA, Leal AM, Latronico AC, Arnhold IJ: Clinical, hormonal, behavioral, and genetic characteristics of androgen insensitivity syndrome in a Brazilian cohort: five novel mutations in the androgen receptor gene. J Clin Endocrinol Metab 2003;88:3241–3250.
5.
Ahmed SF, Cheng A, Dovey L, Hawkins JR, Martin H, Rowland J, Shimura N, Tait AD, Hughes IA: Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab 2000;85:658–665.
6.
Pleskacova J, Hersmus R, Oosterhuis JW, Setyawati BA, Faradz SM, Cools M, Wolffenbuttel KP, Lebl J, Drop SL, Looijenga LH: Tumor risk in disorders of sex development. Sex Dev 2010;4:259–269.
7.
Warne GL, Grover S, Zajac JD: Hormonal therapies for individuals with intersex conditions: protocol for use. Treat Endocrinol 2005;4:19–29.
8.
Bertelloni S, Dati E, Baroncelli GI: Disorders of sex development: hormonal management in adolescence. Gynecol Endocrinol 2008;24:339–346.
9.
Zachmann M, Prader A, Sobel EH, Crigler JF Jr, Ritzen EM, Atares M, Ferrandez A: Pubertal growth in patients with androgen insensitivity: indirect evidence for the importance of estrogens in pubertal growth of girls. J Pediatr 1986;108:694–697.
10.
Papadimitriou DT, Linglart A, Morel Y, Chaussain JL: Puberty in subjects with complete androgen insensitivity syndrome. Horm Res 2006;65:126–131.
11.
Tanner JM, Whitehouse RH: Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976;51:170–179.
12.
Han TS, Goswami D, Trikudanathan S, Creighton SM, Conway GS: Comparison of bone mineral density and body proportions between women with complete androgen insensitivity syndrome and women with gonadal dysgenesis. Eur J Endocrinol 2008;159:179–185.
13.
Van Gelderen HH: Skeletal maturation in the XY female syndrome. Clin Genet 1986;30:199–201.
14.
Doehnert U, Bertelloni S, Richter-Unruh A, Werner R, Hiort O: Hormone profiles in adolescents and adults with complete androgen insensitivity syndrome (abstract). 3rd International Symposium on Disorders of Sex Development, Lübeck, May 20–22, 2011, p 57.
15.
Bertelloni S, Baroncelli GI, Mora S: Bone health in disorders of sex differentiation. Sex Dev 2010;4:270–284.
16.
Kirsch S, Weiss B, Kleiman S, Roberts K, Pryor J, Milunsky A, Ferlin A, Foresta C, Matthijs G, Rappold GA: Localisation of the Y-chromosome stature gene to a 700-kb interval in close proximity to the centromere. J Med Genet 2002;39:507–513.
17.
Brookman RR: Appendix D: Endocrinology of puberty; in McAnarney ER, Kreipe RE Orr DP, Comerci GD (eds): Textbook of Adolescent Medicine. Philadelphia, Saunders, 1992, pp 1180–1183.
18.
Hughes IA, Houk C, Ahmed SF, Lee PA, LWPES/ESPE Consensus Group: Consensus statement on management of intersex disorders. Arch Dis Child 2006;91:554–563.
19.
Hiort O, Reinecke S, Thyen U, Jürgensen M, Holterhus PM, Schön D, Richter-Appelt H: Puberty in disorders of somatosexual differentiation. J Pediatr Endocrinol Metab 2003;16(suppl 2):297–306.
20.
Drobac S, Rubin K, Rogol AL, Rosenfield RL: A workshop on pubertal hormone replacement options in the United States. J Pediatr Endocrinol Metab 2006;19:55–64.
21.
Balsamo A, Bertelloni S, in rappresentanza dei Gruppi di Studio SIEDP di Fisiopatologia della Pubertà & Complicanze Endocrine nelle Malattie Croniche: Trattamento dell’ ipogonadismo in età evolutiva: indagine conoscitiva SIEDP (abstract). XVI Congresso Nazionale SIEDP, Parma, October 11–13, 2007, p 167.
22.
Kiess W, Conway G, Ritzen M, Rosenfield R, Bernasconi S, Juul A, van Pareren Y, de Muinck Keiser-Scharama SMPF, Bourguignon J-P: Induction of puberty in the hypogonadal girl. Practices and attitudes of pediatric endocrinologists in Europe. Horm Res 2002;57:66–71.
23.
Rosenfield RL, Devine N, Hunold JJ, Mauras N, Moshang T Jr, Root AW: Salutary effects of combining early very low-dose systemic estradiol with growth hormone therapy in girls with Turner syndrome. J Clin Endocrinol Metab 2005;90:6424–6430.
24.
Kopper NW, Gudeman J, Thompson DJ: Transdermal hormone therapy in postmenopausal women: a review of metabolic effects and drug delivery technologies. Drug Des Devel Ther 2009;2:193–202.
25.
Nabhan ZM, Dimeglio LA, Qi R, Perkins SM, Eugster EA: Conjugated oral versus transdermal estrogen replacement in girls with Turner syndrome: a pilot comparative study. J Clin Endocrinol Metab 2009;94:2009–2014.
26.
Mauras N, Shulman D, Hsiang HY, Balagopal P, Welch S: Metabolic effects of oral versus transdermal estrogen in growth hormone-treated girls with Turner syndrome. J Clin Endocrinol Metab 2007;92:4154–4160.
27.
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321–333.
28.
Vujovic S, Brincat M, Erel T, Gambacciani M, Lambrinoudaki I, Moen MH, Schenck-Gustafsson K, Tremollieres F, Rozenberg S, Rees M: European Menopause and Andropause Society. EMAS position statement: managing women with premature ovarian failure. Maturitas 2010;67:91–93.
29.
Slob AK, van der Werff ten Bosch JJ, van Hall EV, de Jong FH, Weijmar Schultz WC, Eikelboom FA: Psychosexual functioning in women with complete testicular feminization: is androgen replacement therapy preferable to estrogen? J Sex Marital Ther 1993;19:201–209.
30.
Birnbaum W, Marshall L, Schnabel D, Bals-Pratch M, Richter-Unruh A, Wagner R, Kropf S, Hiort O: Comparison of clinical and metabolic effect of testosterone and estradiol in adult gonadectomised patients with 46,XY DSD due to complete androgen insensitivity (abstract). 3rd International Symposium on Disorders of Sex Development, Lübeck, May 20–22, p 71.
31.
Sobel V, Schwartz B, Zhu YS, Cordero JJ, Imperato-McGinley J: Bone mineral density in the complete androgen insensitivity and 5α-reductase-2 deficiency syndromes. J Clin Endocrinol Metab 2006;91:3017–3023.
32.
Taes Y, Lapauw B, Vandewalle S, Zmierczak H, Goemaere S, Vanderschueren D, Kaufman JM, T’Sjoen G: Estrogen-specific action on bone geometry and volumetric bone density: longitudinal observations in an adult with complete androgen insensitivity. Bone 2009;45:392–397.
33.
Dati E, Bertelloni S, Ghione S, Petracchi A, Baroncelli GI: Bone mineral density in women with complete androgen insensitivity syndrome (abstract). 3rd International Symposium on Disorders of Sex Development, Lübeck, May 20–22, 2011, p 37.
34.
Ferlin A, Pepe A, Gianesello L, Garolla A, Feng S, Giannini S, Zaccolo M, Flacciolli A, Morello R, Agoulnik AI, Foresta C: Mutations in the insulin-like factor-3 receptor are associated with osteoporosis. J Bone Miner Res 2008;23:683–693.
35.
Brain CE, Creighton SM, Mushtaq I, Carmichael PA, Barnicoat A, Honour JW, Larcher V, Achermann JC: Holistic management of DSD. Best Pract Res Clin Endocrinol Metab 2010;24:335–354.
36.
Crowley R, Wolfe I, Lock K, McKee M: Improving the transition between paediatric and adult healthcare: a systematic review. Arch Dis Child 2011;96:548–553.
37.
Prader A, Budliger H: Body measurements, growth velocity and bone age of healthy children up to 12 years of age (longitudinal growth study Zurich) (in German). Helv Paediatr Acta 1977;(suppl 37):1–44.
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