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

The management of disorders of sex development (DSD) has been a problem area for years, partly because clinicians have started to see that not all of their patients grow up to be happy adults content with the gender assigned to them at birth, and partly because of the vigorous activities of patient advocacy organizations who have publicized their unhappiness and disagreement about current practices to the world at large and to politicians in particular. Results from a large number of long-term outcome studies have been published in the last decade and this paper attempts to give an overview of what we now know and what we still do not know about how to obtain a good outcome for our patients. Many studies have focused on a particular disorder and there have been more about congenital adrenal hyperplasia and complete androgen insensitivity (CAIS) than any of the other conditions, even though mixed gonadal dysgenesis is probably more common than CAIS. This is because researchers have wanted to know about the effects of hormones on the brain. There have been studies from a number of different countries, and cultural differences come to the fore in disorders affecting sex and gender. Very few studies have been done in Africa or East Asia so far. Long-term outcome should be studied in every treatment center, but there is a great need for study instruments to be developed that would be robust enough to use in a range of different cultural settings and languages. The studies show that while many patients fare well and are leading productive lives, gender dysphoria has been underestimated in the past and that gender counseling as well as sexual counseling should be part of the multi-disciplinary service available to patients with DSD. More emphasis is also needed on strategies to prevent the development of germ cell cancers. Urological problems in both males and females with DSD have been underestimated and deserve more attention.

Section: Complete Androgen Insensitivity Syndrome (Cais)mentioning

confidence: 99%

Long-Term Outcome of Disorders of Sex Development

Warne

2008

“…Variable results have been reported, but a tendency to reduced BMD values has been found, mainly at the lumbar spine. Lumbar BMD scans below -2.5 standard deviations (SD) (that is the cutoff to define osteoporosis according to WHO) [NIH Consensus, 2001] were reported in 5/10 women [Muñoz-Torres et al, 1995;Soule et al, 1995;Bertelloni et al, 1998;Mizunuma et al, 1998;Tian et al, 2005;Danilovic et al, 2007;Chin et al, 2012] ( Table 1 ). All femoral neck measurements were within the normal range, even though below the 0 SD in 6/9 persons [Soule et al, 1995;Muñoz-Torres et al, 1995;Mizunuma et al, 1998;Bertelloni et al, 1998;Tian et al, 2005;Danilovic et al, 2007;Chin et al, 2012] ( Table 1 ).…”

Section: Bmd Status In Women Living With Cais and Intact Gonadsmentioning

confidence: 99%

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

Bertelloni

Meriggiola²,

Dati

et al. 2017

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.

“…BMD in individuals with 46,XY DSD has been measured mainly in CAIS, but some data are available for individuals with partial AIS (PAIS), 5 ␣ -reductase-2 deficiency and 46,XYGD [Muñoz-Torres et al, 1995;Soule et al, 1995;Vered et al, 1997;Bertelloni et al, 1998;Mizunuma et al, 1998;Marcus et al, 2000;Costa et al, 2001;Tian et al, 2005;Sobel et al, 2006;Danilovic et al, 2007;Dati et al, 2008;Han et al, 2008;Taes et al, 2009]. Results are summarized in table 1 .…”

Section: Xy Dsd: Bone Health In Disorders Of Androgen Biosynthesismentioning

confidence: 99%

“…However, some limitations exist. Data on BMD were mostly collected in single individuals or small samples of patients [Muñoz-Torres et al, 1995;Soule et al, 1995;Vered et al, 1997;Bertelloni et al, 1998;Mizunuma et al, 1998;Costa et al, 2001;Danilovic et al, 2007;Taes et al, 2009] or obtained by cumulating results collected with different bone scanners [Marcus et al, 2000], so introducing some difficulties in the interpretation of the data. In addition, BMD measurements were obtained in heterogeneous populations regarding gonadal status and/or substitutive therapy, with the diagnosis sometimes relying only on clinical and/or endocrine features, because mutational analysis of the AR have not been performed in all of the studies ( table 1 ).…”

Section: Xy Dsd: Bone Health In Disorders Of Androgen Biosynthesismentioning

confidence: 99%

Bone Health in Disorders of Sex Differentiation

Bertelloni

Baroncelli

Mora³

2010

Sex steroids are main regulators of skeletal growth, maturation and mass in both men and women. People with disorders of sex development (DSD) may experience problems in developing normal bone growth, structure and mass, because abnormal sex steroid secretion or action may be operative. In complete androgen insensitivity syndrome several reports documented reduced bone mineral density (BMD). Reduced BMD is evident in patients with not removed or removed gonads, but it is poorer in the latter, mainly when compliance with estrogen replacement therapy is not guaranteed. Large impairment of BMD does not seem to be present in patients with partial androgen insensitivity syndrome or 5α-reductase-2 deficiency, providing that gonads are not removed or that substitutive therapy is optimized. In congenital adrenal hyperplasia, BMD may be impaired as a result of not optimal glucocorticoid administration. In Turner syndrome, impaired BMD may result from the combined actions of estrogen deficiency, low bone dimensions, altered bone geometry, deficient cortical bone, and trabecular bone loss. Optimal estrogen administration seems to be important in preserving bone mass and enhancing trabecular bone volume. On the whole, bone health represents a main clinical issue for the management of persons with disorders of sex differentiation, and well designed longitudinal studies should be developed to improve their bone health and well-being.