Hormonal Management of Complete Androgen Insensitivity Syndrome from Adolescence Onward

Abstract

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.

Characteristic Features of Reproductive Hormone Profiles in Late Adolescent and Adult Females with Complete Androgen Insensitivity Syndrome

“…Our findings would also imply a different approach to HRT in those women with CAIS who underwent gonadectomy. E2 replacement therapy currently aims at much higher estradiol levels in the female reference range, whereas T substitution is not a common practice [Bertelloni et al, 2011]. Malcompliance with HRT due to impaired physical well-being may be related to unphysiological hormone profiles with such therapy.…”

“…However, recent observations indicate that the risk of developing germ cell tumors before and during puberty is low in women with CAIS [Lecca et al, 1988;Cools et al, 2006;Hannema et al, 2006;Looijenga et al, 2007;Hersmus et al, 2008;Wünsch et al, 2012]. For those who underwent gonadectomy, hormone replacement therapy (HRT) is mandatory to induce puberty and improve bone health and well-being [Bertelloni et al, 2011].…”

Gonadectomy in Complete Androgen Insensitivity Syndrome: Why and When?

“…After gonadectomy, continuous and long-term hormone therapy is necessary to achieve induction of puberty and maintenance of sexual function, psychosocial well-being, and bone health [Bertelloni et al, 2011]. So far, there have not been any studies reported that examine different hormonal medications, their dosage, and routes of administration necessary to obtain these aims.…”

Update on the Pathophysiology and Risk Factors for the Development of Malignant Testicular Germ Cell Tumors in Complete Androgen Insensitivity Syndrome

“…Based on these data, and in line with demands from advocacy groups to restrict surgery in DSD children wherever possible, many DSD centers gradually adopted a policy of postponing prophylactic gonadectomy to late adolescence in individuals with CAIS [Hughes et al, 2012]. Such an approach allows for spontaneous breast development and bone mass accrual during puberty through peripheral conversion of androgens to estrogens [Bertelloni et al, 2010[Bertelloni et al, , 2011 without compromising safety regarding tumor development. In addition, informed consent for gonadectomy can be obtained directly from the adolescent girl, alleviating the pressure on parents and promoting psychological adaptation in patients [Siminoff and Sandberg, 2015].…”