Characterization of bone mineral density in male-to-female transsexuals receiving treatment for reassignment surgery: 15 years of follow-up

Background: Cross-sex hormone treatment in male-to-female (M2F) transsexuals appears reasonably safe. Little is known about its long-term use. The aim of our study was to evaluate the effect of long-term high dose estrogens, plus the antiandrogen cyproterone acetate, on bone composition and on biochemical/hormonal parameters in M2F transsexuals. Methods: A retrospective analysis was performed on 45 young M2Fs (mean age 39.5 years; body mass index (BMI) = 22) receiving estrogens (previously 100 mg ethinyl estradiol, now 2–4 mg oral estradiol valerate/day or 100 mg transdermal estradiol/day) plus the antiandrogen cyproterone acetate 100 mg/day. Data were retrieved from 20 subjects after reassignment surgery (mean hormonal treatment duration 15.6 years). A complete hormonal and biochemical assessment, as well as bone biochemical markers (parathyroid hormone (PTH), calcium, phosphorus, alkaline phosphatase and plasma pyridinoline crosslinks), were evaluated. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA). Results: All subjects had suppressed serum testosterone levels (mean = 0.57 nmol/l), whereas serum estradiol levels were within the supraphysiological range (mean = 880 pmol/l). A mild osteopenia at both lumbar spine and femoral neck was observed in 15 out of the 20 (75%) M2Fs (BMD = 0.89 0.14 (mean standard deviation (SD)) g/cm2 versus 1.1 0.09, p < 0.001; lumbar T-score = 1.39 0.84 versus 0.5 1.10, p < 0.0005; femoral T-score = 1.12 0.76 versus 0.08 1.00, p < 0.05, respectively). No differences in plasma crosslink levels or in hormonal and biochemical parameters were found between subjects. Conclusions: Our results indicate that cross-sex hormone treatment of M2Fs, independently of serum testosterone levels, seems acceptably safe over a median treatment period of 15 years in a consistent population of subjects. A protective role for estrogens on bone seems to be present in a minority of subjects