Endocrine Abstracts

Background: Patients with complete androgen insensitivity syndrome (CAIS) who undergo gonadectomy have evidence of reduced bone mineral density (BMD) and perhaps, higher risk of fragility fractures. Because of this, hormonal replacement therapy (HRT), usually in the form of estrogen, is used as patients with CAIS have 46, XY genotypes having androgen receptor abnormalities making them resistant to the effects of androgen. Tibolone, a “selective tissue estrogenic activity regulator” (STEAR), is a synthetic compound with estrogenic (anti-resorptive properties) on bone, preventing bone loss, increasing BMD and preventing fractures in postmenopausal women.

Case Description: A 45-year-old phenotypic woman with no prior history of fractures presents to the clinic for evaluation of primary amenorrhea. Her subsequent evaluation was consistent with a diagnosis of CAIS. She was 171 cm in height and 67 kg in weight (BMI of 29.38 kg/m²). Physical examination was notable for scant androgen-dependent body hair, Tanner stage V breast development, and a blind vaginal pouch. Work-up showed an absent uterus on magnetic resonance imaging, a 46, XY karyotype, and hormonal evaluations consistent with male normative ranges for total testosterone estradiol. She subsequently underwent two gonadectomies (with a 10-month interval) which showed gonads having testicular histology. Dual-energy x-ray absorptiometry revealed osteopenia based on normal female range. Baseline spine T-score was –1.7 (0.960 g/cm²), right total hip T-score was –1.3 (0.841 g/cm²), right femoral neck T-score was –1.0 (0.895 g/cm²), left total hip T-score was –1.7 (0.794 g/cm²), left femoral neck T-score was –1.2 (0.875 g/cm²), and 33 percent left radius T-score was –0.8 (0.809 g/cm²). Additional workups for secondary causes of osteoporosis were unremarkable. Our patient was started on tibolone 2.5 mg daily together with calcium and vitamin D3 supplementation. After one year of treatment, spine BMD increased by 2.3%, right total hip increased by 1.7%, right femoral neck increased by 3.9%, and left femoral neck increased by 1.7%. There was no significant change in the left total hip BMD. She did not experience any adverse drug events on tibolone.

Conclusion: While the efficacy of tibolone in post-menopausal osteoporosis has been demonstrated in literature, its role in the management of post-gonadectomized patients with CAIS has not been documented. We present a patient with CAIS who had increased BMD after one year of tibolone 2.5 mg treatment. A long-term study of tibolone in this rare condition is warranted so effective treatment strategies could be offered to patients to mitigate bone loss especially during early gonadectomy.