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Hormone therapy in transgender patients is safe for bone



Transwomen are more likely to have a lower bone mineral density (BMD) before beginning hormone therapy, compared with male reference populations, but there are no short- or long-term risks to bone health over the life of a transperson who receives hormone therapy, according to a presentation at the annual meeting of the American Society for Bone and Mineral Research.

“Hormonal treatment of transgender people is safe with respect to bone,” said Martin den Heijer, MD, PhD, of the VU University Medical Center in Amsterdam.

At baseline, transwomen have lower bone mass than do male reference populations, said Dr. den Heijer, citing a study that found 25 transwomen had less muscle mass (P less than or equal to .001), strength (P less than or equal to .05), and lower BMD at the hip, femoral neck, and spine (P less than .001), compared with 25 cisgender men in a control group and 941 men in a male reference population (Bone. 2013;54[1]:92-7). In a 2019 study from his own group, Dr. den Heijer said the z score in the lumbar spine for 711 transwomen was -0.9 and the incidence of osteoporosis was 14.2%, compared with a z score of 0.0 and 2.4% incidence of osteoporosis in 543 transmen (J Bone Min Res. 2019;34[3]:447-54).

In the prospective European Network for the Investigation of Gender Incongruence (ENIGI) study, researchers examined short-term effects of hormone therapy on BMD in 144 transwomen and 162 transmen who had a normal body mass index and were mostly white. The percentage of patients who reported they were current smokers was between 25% and 30%, and fewer than 10% said they consumed more than seven units of alcohol per week. Transwomen received estradiol (an oral estradiol valerate at a dose of 4 mg/day or an estradiol patch) together with 100 mg/day of cyproterone acetate, and transmen received testosterone in the form of a gel (50 mg/day), intramuscular esters (250 mg every 2-3 weeks), or intramuscular undecanoate at a dose of 1,000 mg every 12 weeks (J Sex Med. 2016;13[6]:994-9).

After 1 year of treatment, there were significant increases in BMD in transwomen in the lumbar spine (3.67%; 95% confidence interval, 3.20%-4.13%), femoral neck (1.86%; 95% CI, 1.41%-2.31%), and total hip (0.97%; 95% CI, 0.62%-1.31%). Transmen also had increased BMD in the lumbar spine (0.86%; 95% CI, 0.38%-1.35%) and total hip (1.04%; 95% CI, 0.64%-1.44%), with a slight decrease in femoral neck BMD (–0.46%; 95% CI, –1.07% to 0.16%).

Dr. den Heijer also discussed the long-term effects of hormone therapy on BMD in the Amsterdam Cohort of Dysphoria (ACOG) study, which consisted of 711 transwomen and 543 transmen and followed some patients out to 2 years, 5 years, and 10 years after beginning hormone therapy (J Sex Med. 2018;15[4]:582-90). Among transwomen, the median age was 33 years, 68.9% had begun hormone therapy, and 75.3% received a gonadectomy; among transmen, the median age was 25 years, 72.9% had begun hormone therapy, and 83.8% received a gonadectomy. Of these patients, dual-energy x-ray absorptiometry data were available for the lumbar spine BMD for 234 transwomen and 236 transmen at 2 years, 174 transwomen and 95 transmen at 5 years, and 102 transwomen and 70 transmen at 10 years.

Although there was no significant mean change in absolute BMD over the 10-year period, the concentration of estradiol in transwomen and transmen affected change in BMD the longer the transperson was receiving hormone therapy: Transwomen who received an estradiol concentration of 118 pmol/L had a decrease of –0.026% at 2 years, –0.044% at 5 years, and –0.009% at 10 years, compared with a dose of 443 pmol/L (+0.044% at 2 years, +0.025% at 5 years, +0.063% at 10 years), whereas transmen also had decreased BMD at the lowest estradiol concentrations of 95 pmol/L (–0.007% at 2 years, –0.024% at 5 years, +0.010% at 10 years), compared with transmen receiving the highest doses of 323 pmol/L (+0.028% at 2 years, +0.002% at 5 years, +0.053% at 10 years). There was no significant change in BMD in either group at any time point with regard to testosterone concentration.

When the investigators linked these patients to a national statistics database in the Netherlands to evaluate fracture incidence (J Bone Miner Res. 2019 Sep 5. doi: 10.1002/jbmr.3862), pairing five cisgender female controls and five cisgender male controls to every transgender patient, the researchers found transwomen had a higher incidence of osteoporotic fracture of the hip, spine, forearm, and humerus (41.8%), compared with cisgender men (26.6%; P = .014) and cisgender women (36.0%; P = .381). There was not enough information in the study to examine fracture information for transmen, Dr. den Heijer said. Transwomen and transmen who experienced a fracture were more likely to be a current smoker and have lower estradiol concentrations than were transwomen and transmen, respectively, who did not have a fracture.

“Attention for lifestyle factors remains important, especially smoking cessation, vitamin D intake, and regular exercise,” Dr. den Heijer said. “It remains important for everybody, but especially for transgender women.”

Dr. den Heijer reported no relevant conflicts of interest.

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