OBJECTIVE In transsexual people, cross-sex hormone therapy is an important component of medical treatment and results in a complete change in the sex hormone environment. Steroid hormones plays an important role in developing and maintaining bone mass and body composition in both sexes. The aim of this study was to evaluate changes in body composition and bone mineral density (BMD) during cross-sex hormone therapy in transsexuals using gonadotrophin-releasing hormone agonists and intramuscular oestrogens. METHODS 84 male-to-female transsexuals (MtFs) were treated with 10 mg oestradiol-17β valerate every 10 days. The study population was treated with subcutaneous injections of 3.8 mg goserelin acetate every 4 weeks to suppress endogenous sex hormone secretion completely. Endocrine parameters, body composition and BMD after 12 months and after 24 months were compared with baseline values. RESULTS There was a significant decline in gonadotrophins and testosterone, while oestradiol, sex hormone-binding globulin, and high-density lipoprotein levels increased significantly after 12 and 24 months. There was a significant increase in body mass index (BMI), fat mass, and lumbar spine bone mineral density in MtFs during the study period, while lean mass decreased significantly and no effect was observed on femoral bone mineral density. CONCLUSIONS There was an increase in BMI associated with a shift from lean mass to fat mass. There appears to be no risk of osteoporosis developing in MtFs when there is adequate oestrogen substitution, even in the absence of testosterone. Furthermore in comparison with hormone regimes using oral medications, the complication rates appear to be lower in patients receiving gonadotrophin-releasing hormone agonists and intramuscular oestrogens.