Long‐term follow‐up of bone mineral density and bone metabolism in transsexuals treated with cross‐sex hormones

OBJECTIVE: It is unknown whether long term cross-sex hormone treatment affects the human skeleton. We monitored bone mineral density and biochemical markers of bone turnover for 28-63 months in 20 male-to-female transsexuals (M-->F) treated with anti-androgens and oestrogens, and 19 female-to-male transsexuals (F-->M) treated with androgens. They underwent gonadectomy 13-35 months after the start of cross-sex hormone administration. DESIGN: Bone mineral density (BMD) and the markers of bone turnover osteocalcin, alkaline phosphatase, fasting urinary calcium/creatinine and hydroxyproline/creatinine, were measured at baseline, after 1 year and after 28-63 months of cross-sex hormone administration. RESULTS: In oestrogen-treated M-->F, variables of bone turnover decreased significantly with consecutive measurements. BMD had increased significantly after 1 year, but decreased again to baseline levels after 28-63 months of cross-sex hormones. In F-->M, alkaline phosphatase levels increased during the first year. BMD did not change during the first year but had decreased significantly after 28-63 months following ovariectomy. In both M-->F and F-->M, the change of BMD correlated inversely with serum LH and FSH levels. Of all biochemical variables LH levels appeared to be the best predictor of loss of BMD; in the long-term LH levels were more elevated in testosterone-treated F-->M than in oestrogen-treated M-->F transsexuals. CONCLUSION: In M-->F, oestrogen treatment prevented bone loss after testosterone deprivation. In F-->M the testosterone dosage used, associated with a decline in serum oestradiol levels, was unable to maintain bone mass fully in all subjects in the longer term. The inverse relationship between BMD and serum LH levels suggests that the dose of hormone replacement has been too low in subjects with a decline in their BMD. Its cause might be underdosing or non-compliance in some patients. We propose that serum LH levels may be used as a measure of the adequacy of replacement with sex steroids.