Cross-sex pattern of bone mineral density in early onset gender identity disorder I.R. Haraldsen a, ⁎ , E. Haug b , J. Falch b , T. Egeland c , S. Opjordsmoen d a Department of Neuropsychiatry and Psychosomatic Medicine, University of Oslo, The National Hospital, 0027 Oslo, Norway b Centre of Endocrinology, Aker University Hospital, University of Oslo, Norway c Department of Medical Genetics, Ullevaal University Hospital, Norway d Department of Psychiatry, Ullevaal University Hospital, Faculty of Medicine, University of Oslo, Norway Received 14 September 2006; revised 2 April 2007; accepted 14 May 2007 Available online 2 June 2007 Abstract Hormonally controlled differences in bone mineral density (BMD) between males and females are well studied. The effects of cross-sex hormones on bone metabolism in patients with early onset gender identity disorder (EO-GID), however, are unclear. We examined BMD, total body fat (TBF) and total lean body mass (TLBM) in patients prior to initiation of sex hormone treatment and during treatment at months 3 and 12. The study included 33 EO-GID patients who were approved for sex reassignment and a control group of 122 healthy Norwegians (males, n = 77; females, n = 45). Male patients (n = 12) received an oral dose of 50 μg ethinylestradiol daily for the first 3 months and 100 μg daily thereafter. Female patients (n = 21) received 250 mg testosterone enantate intramuscularly every third week. BMD, TBF and TLBM were estimated using dual energy X-ray absorptiometry (DXA). In male patients, the DXA measurements except TBF were significantly lower compared to their same- sex control group at baseline and did not change during treatment. In female patients, the DXA measurements were slightly higher than in same- sex controls at baseline and also remained unchanged during treatment. In conclusion, this study reports that body composition and bone density of EO-GID patients show less pronounced sex differences compared to controls and that bone density was unaffected by cross-sex hormone treatment. © 2007 Elsevier Inc. All rights reserved. Keywords: Gender identity disorder; Bone metabolism; BMD; Estrogen receptors; Estrogen; Testosterone; Gonadotropin Introduction Sex is the major predictor of and contributing factor to skeletal size and shape. Evidence from twin and family studies suggests that between 50 and 85% of the variance in peak bone mass (bony tissue present at the end of the skeletal maturation) is genetically determined (Gueguen et al., 1995; Krall and Dawson-Hughes, 1993). Many candidate genes have been identified that regulate bone mass and susceptibility to osteoporosis, but the full profile of such genes and their variants remain to be defined (Ralston and de Crombrugghe, 2006). Furthermore, bone mineral density (BMD) has also been found to be determined by environmental factors such as diet and lifestyle (Falch, 1982; Lewiecki, 2005). Nevertheless, gonadal hormones have an important modulating impact on bone physiology in both sexes (Turner et al., 1995). Prior to puberty, boys and girls gain BMD at similar rates. After puberty, men tend to acquire greater BMD than women (overview provided by the National Institute of Arthritis Musculoskeletal and Skin Disease at The National Institute of Health, www. niams.nih.gov). The propose role of sex hormones, such as estrogens, in bone physiology is supported by the marked bone loss seen at menopause or after castration, a process mediated by increased osteoclastic bone resorption (Riggs et al., 1998). Menopause leads to accelerated bone loss that plateaus after 5 to 10 years (Gennari et al., 2002). Conversely, several studies have shown a significant effect of estrogen substitution on reduction of bone loss and fracture risk in postmenopausal women (Lindsay, Hormones and Behavior 52 (2007) 334 – 343 www.elsevier.com/locate/yhbeh ⁎ Corresponding author. Fax: +47 23 07 41 70. E-mail address: i.h.haraldsen@psykiatri.uio.no (I.R. Haraldsen). 0018-506X/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.yhbeh.2007.05.012