Complete Androgen Insensitivity and Decreased Bone Mineral Density

Background: Complete androgen insensitivity syndrome (CAIS) is a rare disorder of sex development and primary amenorrhea results in an XY karyotype but female phenotype. Patients with this syndrome have lower bone mineral density (BMD) when compared to age matched controls. Clinical Case: A 44-year-old phenotypic woman with a history of complete androgen insensitivity syndrome presented for follow-up. She was previously on hormone replacement therapy (HRT) at various doses from the age of 12 until her early 30s when her therapy became sporadic. At age 40, she was prescribed transdermal estrogen therapy but discontinued soon after a dermatologic reaction and had not been on any form of hormone replacement since that time. Past medical history was significant for karyotype 46 XY, osteochondritis dissecans of right ankle and bilateral orchiectomy at age 4. She was single with one adopted child. Physical examination showed a height 75 inches, weight 244 lbs and a normal heart, lung, and abdominal examinations. Laboratory results showed estradiol 12.3pg/mL(7.63-42.6), total testosterone 12.0 ng/dL(7-40), FSH 109.6 mIU/mL(25.8-134.8), LH 42.49 mIU/mL(7.7-58.5), anti-mullerian hormone < 0.015 ng/mL (0.26-5.81), inhibin B <7.0 pg/mL(<17), androstenedione 48 ng/dL(41-262), dihydrotestosterone 2.7 ng/dL(4-22) and dehydroepiandrosterone sulfate 209 ng/dL(31-701). A baseline DXA showed low bone density for age with T-score (Z-score) of -2.0 (-1.6) lumbar-spine; -1.6 (-1.2) femoral neck, -1.1 (-0.8) total hip and -2.5 (-2.0) forearm. Discussion:CAIS is caused by a mutation in the androgen receptor (AR) located on the X-chromosome causing complete unresponsiveness to androgen hormone. Karyotype is XY but feminization occurs due to aromatization of androgen to estrogen. Gonadectomy for testicular malignancy prevention is controversial as testicular tumors in CAIS is generally low and gonadal resection subjects individuals to lifelong hormone replacement. These patients also have lower BMD when compared to female or male age matched controls. This is even more apparent in those with removed gonads. Low BMD is exacerbated by poor compliance, inadequate dose or inappropriate HRT. Whether or not fracture risk is higher has yet to be elucidated. Currently, there is no guideline on how to manage low BMD including osteoporosis in this patient population. It is important to counsel patients with CAIS on BMD loss and to ensure optimization of factors that affect bone health including compliance with HRT, vitamin D/calcium intake and exercise. The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or the United States Government.