Clinical Endocrinology (1998) 49, 811–814 811  1998 Blackwell Science Ltd The effects of oestrogen exposure on bone mass in male to female transsexuals S. Reutrakul, B. Ongphiphadhanakul, N. Piaseu, S. Krittiyawong, S. Chanprasertyothin, P. Bunnag and R. Rajatanavin Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand (Received 12 February 1998; returned for revision 20 March 1998; finally revised 17 April 1998; accepted 7 July 1998) Summary OBJECTIVE The importance of oestrogen on bone mineral density (BMD) in males was suggested by reports of patients with oestrogen resistance and aromatase deficiency who demonstrated osteoporo- sis and epiphyseal plate maturation defect despite high testosterone levels. In the present study, we examined the effects of oestrogen exposure on BMD in transsexual men. DESIGN Cross-sectional study of BMD in male to female transsexuals. PATIENTS Subjects consisted of two groups of trans- sexual male dancers aged 16–34 years who did not receive transsexual operations (n ¼ 28). Group 1 (n ¼ 11) and group 2 (n ¼ 17) had used oestrogen for 2 years or less and more than 2 years, respectively. Twenty-four healthy adult males served as controls. RESULTS signs of feminization were presented in both group 1 and group 2, with Tanner’s stage II–III breast development. BMD at various sites were corre- lated only to body weight and not to smoking or milk consumption. After controlling for body weight, it was found that group 2 had significantly higher BMD at L2–4 than controls (1 . 22  0 . 03 vs. 1 . 14  0 . 03 g/cm 2 , P < 0 . 05) and group 1 (1 . 22  0 . 03 vs. 1 . 08  0 . 04 g/cm 2 , P < 0 . 05). BMD at femoral neck was also higher in group 2 compared to controls (1 . 10  0 . 03 vs. 1 . 01  0 . 03 g/cm 2 , P < 0 . 05) and group 1 (1 . 10  0 . 03 vs. 0 . 95  0 . 04 g/cm 2 , P < 0 . 05). Group 1 subjects had lower BMD compared to controls at femoral trochan- ter (0 . 70  0 . 04 vs. 0 . 83  0 . 03 g/cm 2 , P < 0 . 05) and total femur (0 . 96  0 . 05 vs.1 . 07  0 . 03 g/cm 2 , P < 0 . 05). CONCLUSIONS Long-term oestrogen exposure trans- sexual men result in an increase in bone mineral density despite signs of feminization. This suggests that oestrogen has positive effects on bone density in males. The finding of the trend towards reduced bone density in group 1 remains unexplained. Gonadal hormones have an important impact on bone physiology. They participate in the sexual dimorphism of the skeleton, play a role in the maintenance of mineral homeostasis during reproduction and are essential to maintaining bone balance in adults (Turner et al., 1994). The oestrogen-deficient state in post-menopausal women leads to excessive bone loss and osteoporosis. Long-term oestrogen treatment reduces the incidence of fractures of the vertebrae, distal forearm and hip by about 50% (Hutchinson et al., 1979; Weiss et al., 1980; Ettinger et al., 1985). Similarly male hypogonadism is associated with low bone mineral density that improves after testosterone therapy (Finkenstein et al., 1989; Arisaka et al., 1995; Seeman, 1995). Recent clinical observations have suggested the importance of oestrogen on bone in males. Patients with complete androgen insensitivity experience spontaneous pubertal growth, which suggests that oestrogen alone is sufficient for normal pubertal skeletal growth (Zachmann et al., 1986). In contrast, an oestrogen-resistant male patient had severely undermineralized skeleton with biochemical evidence of increased bone resorp- tion, despite having sufficient levels of testosterone (Smith et al., 1994). Moreover, delayed epiphyseal closure and osteope- nia are features of male aromatase deficiency (Conte et al., 1994; Morishima et al., 1995; Bulun, 1996; Mullis et al., 1997), and oestrogen but not testosterone treatment resulted in complete epiphyseal closure and increased spinal bone mineral density (Carani et al., 1997). The above data suggest that oestrogen plays a significant role in male bone physiology. It is unclear, nevertheless, whether oestrogen supplementation would increase bone mass in males without oestrogen deficiency. It was thus the purpose of the present study to examine the impact of oestrogen exposure on bone mass in males by studying male to female transsexuals. Subjects and methods Twenty-eight male to female transsexual dancers were Correspondence: Dr Boonsong Ongphiphadhanakul, Division of Endocrinology and Metabolism, Department of Medicine, Ramathibodi Hospital, Rama 6 Road, Rajthevi, Bangkok 10400, Thailand.