Bone mineral density in women with complete androgen insensivity syndrome

Giulia Gava (IT), ALESSANDRA LAMI (IT), ILARIA MANCINI (IT), VALENTINA MARTELLI (IT), STEFANIA ALVISI (IT), RENATO SERACCHIOLI (IT), MARIA CRISTINA MERIGGIOLA (IT)

[Gava] Gynecology and Pathophysiology of Human Reproduction, S.Orsola-Malpighi Hospital, University of Bologna, Department of Medical and Surgical Sciences (DIMEC), Bologna, Italy, [LAMI] Gynecology and Pathophysiology of Human Reproduction, S.Orsola-Malpighi Hospital, University of Bologna, Department of Medical and Surgical Sciences (DIMEC), Bologna, Italy, [MANCINI] Gynecology and Pathophysiology of Human Reproduction, S.Orsola-Malpighi Hospital, University of Bologna, Department of Medical and Surgical Sciences (DIMEC), Bologna, Italy, [MARTELLI] Gynecology and Pathophysiology of Human Reproduction, S.Orsola-Malpighi Hospital, University of Bologna, Department of Medical and Surgical Sciences (DIMEC), Bologna, Italy, [ALVISI] Gynecology and Pathophysiology of Human Reproduction, S.Orsola-Malpighi Hospital, University of Bologna, Department of Medical and Surgical Sciences (DIMEC), Bologna, Italy, [SERACCHIOLI] Gynecology and Pathophysiology of Human Reproduction, S.Orsola-Malpighi Hospital, Universit

Context – Complete androgen insensitivity syndrome (CAIS) is a rare condition due to complete androgen resistance in androgen-dependent tissues resulting in a female phenotype. One of the most relevant clinical aspects of women with CAIS is bone health since androgens are involved in bone mass and structure acquisition and maintenance. Objective – To assess the impact of hormonal replacement therapy (HRT) with estradiol 2 mg/day on bone density in women with CAIS with intact gonads or with previous gonadectomy. Methods – In this retrospective cross sectional study, we evaluated at the time of the first visit in our center (t0) and after 12 months (t1) the following parameters: bone mineral density (BMD) with DXA scan, anthropometric characteristics and hormonal and metabolic profile. Patients – We enrolled 35 women with CAIS; 24/35 women were already using HRT at t0, 4/35 women had intact gonads. Interventions – After first examination all enrolled women were prescribed with oral estradiol valerate 2 mg/day or transdermal estradiol hemihydrate 2 mg/day. Main Outcome Measure(s) – Mean age was at t0 was 27±10 years. Mean height was 169,0±7,0 cm. At t0 mean BMD was 0,886 ± 0,1 g/cm2 (T-score -2,3±1,1 and Z-score -2.0±1,1) at lumbar spine, and 0,785±0,1 g/cm2 (T-score -1,8±1,1 and Z-score -1,7±0,8) at proximal femur. Osteocalcin and bone alkaline phosphatase were increased, while parathyroid hormone, 25-hydroxyvitamin D and calcium were within normal ranges. At t1 mean BMD was 0,927 ± 0,1 g/cm2 (T-score -1,9 ± 0,9 and Z-score -2,0 ± 0,9) at lumbar spine, and 0,794 ± 0,1 g/cm2 (T-score -1,8 ± 1,0 and Z-score -1,8 ± 0,8) at proximal femur. Result(s) – All women at t0 were ostheopenic in particular at lumbar spine without significant differences between groups. Femoral BMD correlated positively with plasma estradiol and testosterone levels. At t1 there was improvement in lumbar BMD values (p = 0.0068). In our cohort the percentage of women with osteopenia was greater in the sub-group of women gonadectomized before 16 years of age (88.9% vs. 50% p = 0.0342). Conclusions - CAIS is a determining condition for osteopenia especially at the lumbar level, probably for a direct role of the absence of androgenic action. HRT is essential to reduce the alterations of the BMD but it is not enough to normalize it after one year of therapy. A delay in gonadectomy can be preferable for the benefits associated with the normal development of puberty.