High dose estrogen treatment increases bone mineral density in male-to-female transsexuals receiving gonadotropin-releasing hormone agonist in the absence of testosterone

Objective: To study the effect of estrogen (E) on the male skeleton in the absence of testosterone (T). Design: Retrospective analyses of 40 middle-aged transsexuals treated with subcutaneous injections of gonadotropin-releasing hormone agonist every 4 weeks and oral 17-beta-estradiol-valerat 6 mg/day over two years until reassignment surgery. Methods: The bone mineral density (BMD) in the femoral neck and lumbar spine (L2–L4) was measured with dual-energy X-ray absorptiometry at the beginning of cross-sex hormone treatment, after 12 and 24 months, and serum T, E, sex hormone-binding globulin (SHBG), calcitonin (CAL), osteocalcin (OSC), and urinary free deoxypyridinoline (DPD) were measured. Results: After 12 months, a significant increase in BMD in the lumbar spine from 1.2 to 1.234 g/cm2 and after 24 months to 1.274 g/cm2 was observed. There was a significant increase in BMD in the femoral neck area from 1.068 to 1.109 g/cm2 after 24 months. There was a significant decrease in serum T levels from 18.65 to 0.57 nmol/l after 12 months, and to 0.62 nmol/l after 24 months, a significant increase in SHBG levels from 50.09 to 125 nmol/l after 12 months, and to 130 nmol/l after 24 months, and a significant increase in serum E levels from 73.42 to 881.6 pmol/l after 12 months, and to 923.62 pmol/l after 24 months of cross-sex hormone treatment. Serum levels of CAL, OSC and urinary DPD were unchanged. Conclusion: We conclude that high dose E treatment is able to increase BMD significantly in the femoral neck and lumbar spine independently of serum T levels in middle-aged men. There is no risk of osteoporosis developing in male-to-female transsexuals receiving GnRHa when there is an adequate E substitution.