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

Abstract

Objectives: To compare bone mineral density (BMD) and body proportions between women with complete androgen insensitivity syndrome (CAIS) and with gonadal dysgenesis (GD). Setting: Adult Disorders of Sexual Development and Ovarian Failure Clinics at University College London Hospitals. Design: Retrospective cross-sectional study of three groups of women aged 17-58 years with varying degrees of exposure to sex hormones and different combinations of sex chromosomes. Forty-six subjects had CAIS, 18 had GD and 46,XY (GD(XY)), and 25 had GD and 46,XX (GD(XX)). In addition, body proportions of subgroups of these women were analysed. Outcome measures: Oestrogen therapy, karyotype, anthropometry and BMD. Results: Height differed between groups (F ratio 5.2, PZ0.007)), with GD(XX) women being the shortest (meanGS.D.: 1.66G0.10 m), GD(XY) women the tallest (1.74G0.09 m) and CAIS women were in-between (1.70G0.07 m). Delayed gonadectomy resulted in taller stature in CAIS women (PZ0.011). The ratio of lower to upper body length in GD(XY) women was significantly (PZ0.001) greater than that of CAIS women. Multivariate logistic regression analysis (adjusted for age and height) showed that among women with XY karyotype, GD(XY) women were 5.2 times (95% confidence interval (CI): 1.3-20.1, PZ0.018) more likely than CAIS women to have a low hip BMD. This difference was not evident among women with GD of different karyotypes (PZ0.938). Spinal BMD did not differ between subject groups. Further adjustment for oestrogen replacement did not alter these relationships. Conclusions: Taller stature in late gonadectomised CAIS women suggests an oestrogen deficiency in these women prior to gonadectomy. Increased lower to upper body ratio in GD(XY) women compared with the other groups implies that these subjects have the greatest degree of oestrogen deficiency in puberty. Androgen rather than sex chromosomes may play an important role in cortical bone mineralisation in CAIS women, probably via estrogen receptor-a either directly or via aromatisation during critical periods of growth prior to gonadectomy.

Hormonal Management of Complete Androgen Insensitivity Syndrome from Adolescence Onward

“…Recent data in patients with CAIS and mutations in AR gene, followed from infancy to late adolescence, substantially confirmed such data, showing that mean adult height was closer to median male target height than female target height [10]. Han et al [12] reported that the adult height of women with CAIS and removed gonads at puberty or at older age was significantly higher than those who underwent gonadectomy before puberty (172 vs. 165 cm, respectively). In the same study, the lower to upper body ratio was intermediate between that of females and males [12].…”

“…Han et al [12] reported that the adult height of women with CAIS and removed gonads at puberty or at older age was significantly higher than those who underwent gonadectomy before puberty (172 vs. 165 cm, respectively). In the same study, the lower to upper body ratio was intermediate between that of females and males [12]. …”

Androgen Insensitivity Syndrome (AIS)

“…14 Patients in whom gonadectomy is delayed are even taller, suggesting a relative oestrogen defi ciency before gonadectomy. 15 However, no evidence shows that girls with complete androgen insensitivity syndrome start puberty later than girls without the syndrome. 16 The enlarged adult stature in the syndrome is mainly due to the eff ect of the growth-controlling region on the long arm of the Y chromosome, but genome-wide association studies have identifi ed several loci that aff ect adult height.…”

Androgen Insensitivity Syndrome (AIS)

“…15 However, no evidence shows that girls with complete androgen insensitivity syndrome start puberty later than girls without the syndrome. 16 The enlarged adult stature in the syndrome is mainly due to the eff ect of the growth-controlling region on the long arm of the Y chromosome, but genome-wide association studies have identifi ed several loci that aff ect adult height.…”

“…77 No defi nitive evidence shows that bone mineral density is less aff ected in women who had late gonadectomies than in women who had early gonadectomies, although those who had the procedure later in life are substantially taller than those who had early gonadectomies. 78,79 Women with complete androgen insensitivity syndrome do not seem to have an increased risk of fractures. Measurement of bone density at presentation in the case of young women with complete androgen insensitivity syndrome and at 2 yearly inter vals is a useful index of the eff ectiveness of hormone replacement (unpublished).…”