Cardiometabolic Effects of Gender-Affirming Hormone Therapy in Transgender Youth

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Transgender youth on gender-affirming hormone therapy have differences in their percent fat and lean mass compared with cisgender youth.

Gender-affirming hormone therapy is associated with significant differences in body composition and cardiometabolic health between transgender and cisgender youth, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

Previous studies have shown that estradiol treatment for transgender women is associated with a higher incidence of stroke and venous thromboembolism compared with cisgender women and men. The risk for myocardial infarction was found to be higher in both transgender women treated with estrogen and transgender men treated with testosterone compared with cisgender women. Both transgender men and women gained weight on gender-affirming hormone therapy.

As no data are available on adolescents starting gender-affirming hormone therapyand few studies compared the results with cisgender subjects, the goal of the current study was to assess markers of cardiometabolic health in transgender and cisgender adolescents in the United States. The researchers evaluated insulin sensitivity and body composition in adolescent transgender females and males receiving estradiol or testosterone treatment, respectively, matched to cisgender females and males of the same body mass index (BMI) and either age or pubertal stage.

The pilot cross-sectional study ( identifier: NCT02550431) was conducted between 2016 and 2018 in an academic regional transgender referral center at Children’s Hospital Colorado in Aurora. Transgender youth up to age 21 years were eligible to participate if they had been on either testosterone or estradiol treatment for ≥3 months.

The study cohort included 19 transgender males matched to 19 cisgender males and 42 cisgender females, 11 transgender females matched to 23 cisgender females, and 13 transgender females matched to 24 cisgender males.

Body composition was measured using dual-energy x-ray absorptiometry in all studies. Insulin sensitivity was estimated by the inverse of the fasting insulin concentration (1/[fasting insulin]), which is correlated with insulin sensitivity measured with a hyperinsulinemic euglycemic clamp.

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In transgender males, total body fat was lower compared with cisgender females (29%±7% vs 33%±7%, respectively; P =.002) and higher compared with cisgender males (28%±7% vs 24%±9%, respectively; P =.047). Furthermore, they had higher lean body mass compared with cisgender females (68%±7% vs 64%±7%, respectively; P =.002) and lower compared with cisgender males (69% vs 73%, respectively; P =.029). There were no differences in insulin sensitivity between the groups.

As for transgender females, they had lower BMI compared with cisgender females (31%±7% vs 35%±8%, respectively; P =.033), and higher lean body mass (66%±6% vs 62%±7%, respectively; P =.032). Compared with cisgender males, transgender females had higher BMI (28%±6% vs 20%±10%, respectively; P =.001) and lower lean body mass (69%±5% vs 77%±9%, respectively; P =.001). Transgender females were more insulin resistant compared with cisgender males (P =.011).

The researchers acknowledged several study limitations, including cross-sectional design, lack of available matched subjects for all patients, and small sample size.

“Based on the results of this pilot study, further exploration is needed to understand the impact of starting testosterone or estradiol treatment in adolescence, with or without prior pubertal blockade, on short- and long-term cardiometabolic health,” concluded the researchers.

Disclosure: Natalie J. Nokoff disclosed previously consulting for Antares Pharma, Inc.

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Nokoff NJ, Scarbro SL, Moreau KL, et al. Body composition and markers of cardiometabolic health in transgender youth compared to cisgender youth [published online September 23, 2019]. J Clin Endocrinol Metab. doi:10.1210/clinem/dgz029