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Concerns about the effects of gender‐affirming hormonal treatment (HT) on bone mineral density (BMD) in transgender people exist, particularly regarding the decrease in estrogen concentrations in transmen. Although it is known that HT is safe for BMD in the short term, long‐term follow‐up studies are lacking. Therefore this study aimed to investigate the change in BMD during the first 10 years of HT, to determine whether HT is safe and if assessing BMD during HT is necessary. A follow‐up study was performed in adult transgender people receiving HT at the VU University Medical Center Amsterdam between 1998 and 2016. People were included if they were HT naive and had a dual‐energy X‐ray absorptiometry (DXA) scan at the start of HT. Follow‐up DXA scans performed after 2, 5, and/or 10 years of HT were used for analyses. The course of BMD of the lumbar spine during the first 10 years of HT was analyzed using multilevel analyses. A total of 711 transwomen (median age 35 years; IQR, 26 to 46 years) and 543 transmen (median age 25 years; IQR, 21 to 34 years) were included. Prior to the start of HT, 21.9% of transwomen and 4.3% of transmen had low BMD for age (Z‐score < –2.0). In transwomen lumbar spine BMD did not change (+0.006; 95% CI, –0.005 to +0.017), but lumbar spine Z‐score increased by +0.22 (95% CI, +0.12 to +0.32) after 10 years of HT. Also in transmen lumbar spine BMD did not change (+0.008; 95% CI, –0.004 to +0.019), but lumbar spine Z‐score increased by +0.34 (95% CI, +0.23 to +0.45) after 10 years of HT. This study showed that HT does not have negative effects on BMD, indicating that regularly assessing BMD during HT is not necessary. However, a high percentage of low BMD was found prior to HT, especially in transwomen. Therefore, evaluation of BMD before start of HT may be considered. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

Sex steroids are important determinants of bone acquisition and bone homeostasis. Cross-sex hormonal treatment (CHT) in transgender persons can affect bone mineral density (BMD). The aim of this study was to investigate in a prospective observational multicenter study the first-year effects of CHT on BMD in transgender persons. A total of 231 transwomen and 199 transmen were included who completed the first year of CHT. Transwomen were treated with cyproterone acetate and oral or transdermal estradiol; transmen received transdermal or intramuscular testosterone. A dual-energy X-ray absorptiometry (DXA) was performed to measure lumbar spine (LS), total hip (TH), and femoral neck (FN) BMD before and after 1 year of CHT. In transwomen, an increase in LS (+3.67%, 95% confidence interval [CI] 3.20 to 4.13%, p < 0.001), TH (+0.97%, 95% CI 0.62 to 1.31%, p < 0.001), and FN (+1.86%, 95% CI 1.41 to 2.31%, p < 0.001) BMD was found. In transmen, TH BMD increased after 1 year of CHT (+1.04%, 95% CI 0.64 to 1.44%, p < 0.001). No changes were observed in FN BMD (-0.46%, 95% CI -1.07 to 0.16%, p = 0.144). The increase in LS BMD was larger in transmen aged ≥50 years (+4.32%, 95% CI 2.28 to 6.36%, p = 0.001) compared with transmen aged <50 years (+0.68%, 95% CI 0.19 to 1.17%, p = 0.007). In conclusion, BMD increased in transgender persons after 1 year of CHT. In transmen of postmenopausal age, the LS BMD increased more than in younger transmen, which may lead to the hypothesis that the increase in BMD in transmen is the result of the aromatization of testosterone to estradiol. © 2017 American Society for Bone and Mineral Research.

Concerns about bone health in transgender people using gender‐affirming hormonal treatment (HT) exist, but the fracture risk is not known. In this nationwide cohort study, we aimed to compare the fracture incidence in transgender people using long‐term HT with an age‐matched reference population. All adult transgender people who started HT before 2016 at our gender‐identity clinic were included and were linked to a random population‐based sample of 5 age‐matched reference men and 5 age‐matched reference women per person. Fracture incidence was determined using diagnoses from visits to hospital emergency rooms nationwide between 2013 and 2015. A total of 1089 trans women aged <50 years (mean 38 ± 9 years) and 934 trans women aged ≥50 years (mean 60 ± 8 years) using HT for median 8 (interquartile range [IQR] 3–16) and 19 (IQR 11–29) years, respectively, were included. A total of 2.4% of the trans women aged <50 years had a fracture, whereas 3.0% of the age‐matched reference men (odds ratio [OR] = 0.78, 95% confidence interval [CI] 0.51–1.19) and 1.6% of the age‐matched reference women (OR = 1.49, 95% CI 0.96–2.32) experienced a fracture. In trans women aged ≥50 years, 4.4% experienced a fracture compared with 2.4% of the age‐matched reference men (OR = 1.90, 95% CI 1.32–2.74) and 4.2% of the age‐matched reference women (OR = 1.05, 95% CI 0.75–1.49). A total of 1036 trans men (40 ± 14 years) using HT for median 9 (IQR 2–22) years were included. Fractures occurred in 1.7% of the trans men, 3.0% of the age‐matched reference men (OR = 0.57, 95% CI 0.35–0.94), and 2.2% of the age‐matched reference women (OR = 0.79, 95% CI 0.48–1.30). In conclusion, fracture risk was higher in older trans women compared with age‐matched reference men. In young trans women, fracture risk tended to be increased compared with age‐matched reference women. Fracture risk was not increased in young trans men. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

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