Bone health in complete androgen insensitivity syndrome: a comprehensive assessment in a large adult cohort
Eriselda Profka, Alessandra Mangone, Laura Cocchi, Maria Cristina Meriggiola, Maria Balzo, Elisa Restelli, Maria Francesca Bedeschi, Alfredo Berrettini, Daniela Alberico, Claudia Giavoli, Giulia Rodari, Giovanna MantovaniAbstract
Objective
Low bone mineral density (BMD) has been reported in individuals with complete androgen insensitivity syndrome (CAIS), but data on bone health, particularly on morphometric fractures, remain limited and heterogeneous. This study aimed to comprehensively assess bone health in a large monocentric cohort of adult women with CAIS.
Design
Cross-sectional study including 46 adults with CAIS (age 34 ± 8.7 years), 41 gonadectomized and 5 with gonads (age 34.6 ± 8.4 and 29.6 ± 7.5 years, respectively).
Methods
Bone health was assessed through dual-energy X-ray absorptiometry, vertebral morphometry and bone turnover markers. Hormonal levels and additional risk factors (eg, celiac disease, calcium and vitamin D intake) were evaluated. Among gonadectomized patients, all but 4 were receiving hormonal replacement therapy (HRT): 16 transdermal estradiol, 17 oral estradiol, and 4 testosterone.
Results
Lumbar spine BMD resulted impaired (mean Z-score = −1.78 ± 1) in both groups, with Z-score <−2 in 47.8% of the cohort. Femoral BMD was less affected (total hip −0.6 ± 1, femoral neck −0.77 ± 1), particularly in those with gonads. Fragility fractures rate was 8.7% (median age = 39 years). Bone turnover markers resulted increased compared with age-matched controls. No significant differences were found among HRT regimes. To enhance statistical power, retrospective BMD data from 27 additional individuals with CAIS were included. The expanded sub-analysis on 73 women confirmed no significant differences in BMD across HRT regimes.
Conclusions
Young adults with CAIS show impaired lumbar BMD and a notable prevalence of fragility fractures, with similar findings across gonadectomy status and HRT regimen. Treatment should be optimized considering hormonal levels and BMD.