Cross-sex hormone therapy (CSHT) has been associated with changes in bone and lean/fat mass. This study assessed bone mineral density (BMD), appendicular lean mass (ALM), and total fat mass in transwomen undergoing CSHT. We evaluated 142 transwomen (mean age: 33.7 ± 10.3 years; BMI: 25.4 ± 4.6; 86.6% with previous CSHT) during the first 3 months of regular oestrogen treatment (with or without anti-androgens). A reference group including 22 men and 17 cis women was also studied. Clinical and hormonal evaluation and dual-energy X-ray absorptiometry (DXA). Bone mineral density was similar in trans and reference women, and lower at all sites in transwomen vs men. Low bone mass for age was observed in 18% of transwomen at baseline vs none of the reference women or men. Appendicular lean mass and total fat mass were positively correlated with L1-L4 BMD, explaining 14.9% of the observed variation in lumbar spine BMD and 20.6% of the variation in total femur BMD. Appendicular lean mass was similar in trans and reference women, and lower in transwomen vs men. Total fat mass was lower in trans vs reference women. Densitometry was repeated after a mean of 31.3 ± 6.5 months in 46 transwomen. There was a significant increase in total fat mass and a significant decrease in ALM. Bone mineral density remained stable over time. The fairly high prevalence of low bone mass in this sample of transwomen from southern Brazil seems to be related to lower ALM. Non-pharmacological lifestyle-related strategies for preventing bone loss could be beneficial for transgender women receiving long-term CSHT.