May 22, 2019
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Hormone therapy does not worsen bone health in transgender adults

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Transgender adults who initiated gender-affirming hormone therapy experienced decreased bone resorption and increased bone mineral density at 1 year, according to findings published in the Journal of Bone and Mineral Research.

“As the transgender population receiving HT increases worldwide, more transgender people are possibly at risk for lower bone quality and associated problems regarding bone health,” Mariska C. Vlot, MD, of the department of internal medicine at the Center of Expertise on Gender Dysphoria at Amsterdam University Medical Center, and colleagues wrote in the study background. “Therefore, the aim of this study is to investigate the change in bone turnover markers and to evaluate the correlations with changes in BMD in adult transgender people during their first year of HT.”

Vlot and colleagues analyzed data from 253 transgender adults recruited from the Center of Expertise on Gender Dysphoria between June 2012 and April 2016, including 121 transgender women (median age, 30 years) and 132 transgender men (median age, 24 years). Transgender women were treated with oral cyproterone acetate (50-100 mg daily) with estrogen (oral or patch). Transgender men were treated with testosterone gel (50 mg daily, dermal application), testosterone esters (250 mg ever 2 to 3 weeks) or testosterone undecanoate (1,000 mg every 12 weeks). Participants provided blood samples at outpatient visits every 3 months. Researchers recorded levels of estradiol and the bone turnover markers procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase (ALP), C-terminal telopeptide (CTX) and sclerostin and measured bone density via DXA at baseline and 1 year. Patients were stratified by both age (18-30 years, 30-50 years and > 50 years) and sex steroid concentration.

“By using these separate age groups, age-related differences in BMD due to decreasing bone mass with increasing age after reaching peak bone mass is accounted for, as it is expected that bone mass decreases throughout time,” the researchers wrote.

Among transgender women, median estradiol increased by 128% and median testosterone decreased by 96% during the first year of gender-affirming HT. Among transgender men, median estradiol increased 26% and median testosterone increased by 2,248% during the first year of HT, according to researchers.

For transgender women, ALP, CTX and sclerostin decreased by a mean of 19%, 11% and 18%, respectively, after 1 year of HT, with results persisting after adjustment for changes in BMI, smoking status, alcohol use and vitamin D level. There were no between-group differences observed across age groups.

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For transgender men, P1NP, ALP and sclerostin increased by a mean of 33%, 16% and 15%, respectively, after 1 year of HT, with results persisting after adjustment. However, in analysis by age group, transgender men aged at least 50 years experienced a decrease in all bone turnover markers and had a lower estrogen concentration at baseline due to their postmenopausal status before initiating HT, according to researchers.

Among transgender women, an increase in sclerostin was associated with a decrease in total hip BMD; however, there were no other observed associations between bone turnover markers and femoral neck BMD. Among transgender men, only P1NP showed a modest, negative correlation with total hip and femoral neck BMD after 1 year of HT, according to researchers, whereas CTX showed a modest, negative correlation with lumbar spine BMD.

“This study shows that 1 year of HT does not result in deleterious effects on bone health in transgender people,” the researchers wrote. “Despite these results, effects after multiple years of HT, particularly for younger trans men, are of great interest to study in the future. Given the still increasing incidence and need for treatment of transgender people, additional studies should therefore be performed to evaluate the longer-term relationships between change in bone turnover, BMD and fracture risk during HT in transgender people.” – by Regina Schaffer

Disclosures: Abbott supported this study with an unrestricted grant. The authors report no relevant financial disclosures.