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

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, P=0.007)), with GD(XX) women being the shortest (mean+/-s.d.: 1.66+/-0.10 m), GD(XY) women the tallest (1.74+/-0.09 m) and CAIS women were in-between (1.70+/-0.07 m). Delayed gonadectomy resulted in taller stature in CAIS women (P=0.011). The ratio of lower to upper body length in GD(XY) women was significantly (P=0.001) 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, P=0.018) more likely than CAIS women to have a low hip BMD. This difference was not evident among women with GD of different karyotypes (P=0.938). 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-alpha either directly or via aromatisation during critical periods of growth prior to gonadectomy.