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Long-term HT use not associated with fracture risk among transgender women
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A Dutch cohort of older transgender women prescribed long-term gender-affirming hormone therapy had a 3-year fracture risk that was comparable to that of cisgender women, according to findings published in the Journal of Bone and Mineral Research.
“Fracture risk in trans women aged at least 50 years was higher compared with an age-matched male population, but similar if compared with an age-matched female population,” Martin den Heijer, MD, PhD, professor of internal medicine at Vrije University in Amsterdam, told Endocrine Today. “Among trans women aged 50 years and younger, fracture risk was in between the risk of age-matched men and women. The general conclusion is that transgender HT is safe with respect to fracture risk, although concern remains especially for older trans women.”
In a retrospective study, den Heijer and colleagues analyzed data from 1,089 transgender women younger than 50 years (mean age, 38 years), 934 transgender women aged at least 50 years (mean age, 60 years) and 1,036 transgender men (mean age, 40 years), who participated in the Amsterdam Cohort of Gender Dysphoria study, who visited the gender identity clinic at Amsterdam University Medical Center and initiated HT before 2016, each paired with five age-matched men and five age-matched women per transgender person, using data from Statistics Netherlands. Researchers assessed fracture incidence using diagnoses from visits to hospital EDs nationwide between 2013 and 2015.
Median HT use was 8 years for transgender women younger than 50 years, 19 years for transgender women aged at least 50 years and 9 years for transgender men.
Comparable fracture risk
During 3 years of follow-up, fractures occurred in 3.3% of transgender women (n = 67), 2.7% of the age-matched reference men (n = 275) and 2.8% of age-matched reference women (n = 283). Overall fracture incidence was not increased in transgender women compared with age-matched reference men (OR = 1.23; 95% CI, 0.93-1.61) or with age-matched reference women (OR = 1.19; 95% CI, 0.91-1.56). Among transgender women, 41.8% of all fractures occurred at the hip, spine, forearm or humerus vs. 26.6% among age-matched reference men (P = .014) and 36% among age-matched reference women (P = .381).
In age-stratified analyses, 2.4% of transgender women younger than 50 years sustained a fracture, as did 3% of age-matched reference men, for an OR of 0.78 (95% CI, 0.51-1.19), and 1.6% of the age-matched reference women, for an OR of 1.49 (95% CI, 0.96-2.32). Among transgender women aged at least 50 years, 4.4% sustained a fracture vs. 2.4% of age-matched reference men (OR = 1.9; 95% CI, 1.32-2.74) and 4.2% of age-matched reference women (OR = 1.05; 95% CI, 0.75-1.49). In multivariable analysis, age in 2015 (per year, OR = 1.05; 95% CI, 1.02-1.08) and T-score at the lumbar spine (per 1 point, OR = 0.75; 95% CI, 0.59-0.96) were associated with fracture risk; however mean BMI (per point, OR = 1.04; 95% CI, 0.97-1.11) and age at start of HT (per year, OR = 0.98; 95% CI, 0.95-1.01) were not associated with an increased fracture risk.
“Control women usually have normal BMD before menopause, but it decreases during menopause because [of] the loss of estrogen,” the researchers wrote. “Trans women, however, have low BMD but, in our center, do not stop or lower estrogen therapy at the age of 50 years and therefore do not experience a decrease in BMD because of the loss of estrogen. This might explain why the fracture risk becomes similar in trans women compared with age-matched reference women after the age of 50 years, but higher than age-matched reference men.”
Low risk for transgender men
Among transgender men, 1.7% sustained a fracture during 3 years of follow-up, as did 3% of age-matched reference men (n = 155) and 2.2% of age-matched reference women (n = 114). The fracture risk for transgender men was similar to that of age-matched reference women (OR = 0.79; 95% CI, 0.48-1.3) but lower compared with age-matched reference men (OR = 0.57; 95% CI, 0.35-0.94). In multivariable analyses, researchers observed no associations between fracture risk and age in 2015, age at start of HT, mean BMI, smoking status or T-score at the lumbar spine.
The researchers noted that, although the transgender population used HT long term, the overall population was young.
“As most fractures occur at higher age, only the fracture risk at younger ages was assessed in this study,” the researchers wrote. “The effects of HT on fracture risk at old age and the etiology of the fractures therefore remain topics for further research.” – by Regina Schaffer
For more information:
Martin den Heijer, MD, PhD, can be reached at VU University Medical Center, Department of Internal Medicine, Section of Endocrinology, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands; email: m.denheijer@amsterdamumc.nl.
Disclosures: The authors report no relevant financial disclosures.
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