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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., (© 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.)

Sex steroids play a key role in bone turnover and preserving BMD; hence, gender-affirming hormone treatment (HT) in transgender people affects bone metabolism. Most studies have looked into the effect of HT on changes in BMD; however, they do not provide insights into changes in bone metabolism caused by HT. This study investigated changes in bone turnover markers (BTMs) and sclerostin, as well as their correlations with change in BMD in transwomen and transmen during the first year of HT. Transwomen received estradiol and antiandrogens; transmen received testosterone. Sclerostin; P1NP; alkaline phosphatase (ALP); CTx; and BMD of the total hip, the femoral neck, and the lumbar spine were evaluated at baseline and after 1 year of HT. There were 121 transwomen (median age 30 years, interquartile range [IQR] 24 to 41 years) and 132 transmen (median age 24 years, IQR 21 to 33 years) included in the study. In transwomen, ALP decreased in 19% (95% CI, -21 to-16), CTx in 11% (95% CI, -18 to-4), and sclerostin in 8% (95%CI, -13 to-4) of study participants after 1 year of HT. In contrast, in transmen P1NP, ALP, and sclerostin increased in 33% (95% CI, 24 to 42), 16% (95% CI, 12 to 20), and 15% (95% CI, 10 to 20) of study participants, respectively, after 1 year of HT. No age differences were seen in transwomen, whereas in transmen aged ≥50 years a decrease in all BTMs was found in contrast with the other age groups. These transmen had low estrogen concentration at the start of HT based on their postmenopausal state before the start of HT; their estradiol concentrations increased during testosterone treatment. Changes in BTMs and BMD were weakly correlated (correlation coefficient all <0.30). To conclude, 1 year of HT resulted in decreased bone turnover in transwomen and older transmen, whereas it increased in younger transmen. The decrease in bone resorption in older transmen shows the importance of estrogen as a key regulator of bone turnover. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc., (© 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.)

Background: Gender-affirming hormonal treatment (HT) in adult transgender people influences bone mineral density (BMD). Besides BMD, bone geometry and trabecular bone score are associated with fracture risk. However, it is not known whether bone geometry and TBS changes during HT., Purpose: To investigate the bone geometry and TBS in adult transgender people at different time points, up to 25 years, of HT., Methods: A total of 535 trans women and 473 trans men were included, who were divided into three groups at time of their DXA: 20-29 years, 30-39 years, and 40-59 years. Subsequently, each group was divided into different HT durations: baseline, or after 5, 15, or 25 years of HT. Hip structure analysis was performed to measure subperiosteal width, endocortical diameter, average cortical thickness, and section modulus. TBS was calculated based on lumbar spine DXA images., Results: In trans women in all age groups and in young trans men, no differences were observed in periosteal width, endocortical diameter, average cortical thickness, and section modulus for different durations of HT. In trans men aged 40-59 years, subperiosteal width, endocortical diameter, and section modulus were slightly higher in the groups who were using HT compared to the (peri- or postmenopausal) baseline group. In younger trans women, TBS tended to be higher in those using HT compared to the baseline groups, and in older trans women TBS was higher in those using HT for 25 years versus baseline (+0.04, 95%CI +0.00; +0.08). In younger trans men, TBS tended to be lower in those who used HT compared to the baseline groups, and in older trans men TBS was lower in those using 5 years HT versus baseline (-0.05, 95%CI -0.08; -0.01)., Conclusion: No differences in cortical bone geometry parameters were found during different HT-durations. TBS increased in trans women and decreased in trans men, indicating that estrogens have positive effects on TBS. These data may be helpful in determining what sex reference values for calculating T-scores and Z-scores in adult transgender people should be used., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Context: Total 25-hydroxyvitamin D [25(OH)D] is mainly bound to vitamin d-binding protein (DBP). Bioavailable 25(OH)D consists of albumin-bound and free 25(OH)D and is available for metabolic processes. As sex steroids influence DBP, hormonal treatment (HT) in transgender people might affect DBP and consequently the available 25(OH)D. Total 25(OH)D might therefore not well represent bioavailable and free 25(OH)D., Objective: To investigate the effects of HT on DBP, and total, bioavailable, and free 25(OH)D, and to assess whether total 25(OH)D well represents bioavailable and free 25(OH)D., Design: A prospective study., Setting: A university hospital., Participants: Twenty-nine transwomen and 30 transmen., Intervention: Estradiol and cyproterone acetate in transwomen, and testosterone in transmen., Main Outcome Measures: DBP, total 25(OH)D, free 25(OH)D, and albumin were measured at baseline and after 3 months of HT, and deseasonalized total 25(OH)D and bioavailable 25(OH)D were calculated., Results: DBP changed with +5% (95% CI, -0% to 10%; P = 0.06) in transwomen and with -3% (95% CI: -9% to 3%; P = 0.34) in transmen. No significant changes were found in total 25(OH)D, free, and bioavailable 25(OH)D concentrations. Total 25(OH)D was well correlated with bioavailable (R2, 0.75) and free (R2, 0.76) 25(OH)D., Conclusions: DBP tended to increase in transwomen, but did not change in transmen. HT did not influence free 25(OH)D, total 25(OH)D, and bioavailable 25(OH)D concentrations in transwomen and transmen. As total 25(OH)D represents bioavailable and free 25(OH)D well, HT in transgender people does not interfere with the assessment of vitamin D status., (Copyright © 2019 Endocrine Society.)

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., (© 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.)

Background: Over the past decade, the number of people referred to gender identity clinics has rapidly increased. This raises several questions, especially concerning the frequency of performing gender-affirming treatments with irreversible effects and regret from such interventions., Aim: To study the current prevalence of gender dysphoria, how frequently gender-affirming treatments are performed, and the number of people experiencing regret of this treatment., Methods: The medical files of all people who attended our gender identity clinic from 1972 to 2015 were reviewed retrospectively., Outcomes: The number of (and change in) people who applied for transgender health care, the percentage of people starting with gender-affirming hormonal treatment (HT), the estimated prevalence of transgender people receiving gender-affirming treatment, the percentage of people who underwent gonadectomy, and the percentage of people who regretted gonadectomy, specified separately for each year., Results: 6,793 people (4,432 birth-assigned male, 2,361 birth-assigned female) visited our gender identity clinic from 1972 through 2015. The number of people assessed per year increased 20-fold from 34 in 1980 to 686 in 2015. The estimated prevalence in the Netherlands in 2015 was 1:3,800 for men (transwomen) and 1:5,200 for women (transmen). The percentage of people who started HT within 5 years after the 1st visit decreased over time, with almost 90% in 1980 to 65% in 2010. The percentage of people who underwent gonadectomy within 5 years after starting HT remained stable over time (74.7% of transwomen and 83.8% of transmen). Only 0.6% of transwomen and 0.3% of transmen who underwent gonadectomy were identified as experiencing regret., Clinical Implications: Because the transgender population is growing, a larger availability of transgender health care is needed. Other health care providers should familiarize themselves with transgender health care, because HT can influence diseases and interact with medication. Because not all people apply for the classic treatment approach, special attention should be given to those who choose less common forms of treatment., Strengths and Limitations: This study was performed in the largest Dutch gender identity clinic, which treats more than 95% of the transgender population in the Netherlands. Because of the retrospective design, some data could be missing., Conclusion: The number of people with gender identity issues seeking professional help increased dramatically in recent decades. The percentage of people who regretted gonadectomy remained small and did not show a tendency to increase. Wiepjes CM, Nota NM, de Blok CJM, et al. The Amsterdam Cohort of Gender Dysphoria Study (1972-2015): Trends in Prevalence, Treatment, and Regrets. J Sex Med 2018;15:582-590., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

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., (© 2017 American Society for Bone and Mineral Research.)