Gender-affirming HT alters body composition during adolescence
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Transgender adolescents prescribed gender-affirming hormone therapy have substantial differences in body composition when compared with cisgender youths, with body fat and lean mass measurements intermediate between BMI-matched cisgender males and females, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
The findings from a pilot, cross-sectional study suggest that such changes in body composition may have consequences for the cardiometabolic health of transgender adolescents, according to researchers.
“Transgender adolescents on gender-affirming hormone therapy had body composition measures in between those of cisgender males and females, matched on similar characteristics,” Natalie Nokoff, MD, assistant professor of pediatrics at the SOAR Clinic at Children’s Hospital Colorado, told Endocrine Today. “Transgender females were more insulin resistant than cisgender males.”
Nokoff and colleagues analyzed data from transgender youths (aged 15.1-19.8 years; 19 transgender males; 11 transgender females) prescribed estradiol or testosterone for at least 3 months, recruited between 2016 and 2018 from the TRUE Center for Gender Diversity at Children’s Hospital Colorado. Researchers matched participants by BMI percentile with healthy, cisgender controls using data from Colorado Resistance to Insulin in Type 1 and Type 2 Diabetes (RESISTANT) study and the Health Influences in Puberty study. All participants were Tanner stage 5, except for two transgender males for whom staging was unavailable. All participants underwent body composition measurements via DXA and pubertal staging and provided fasting blood samples to assess lipid, glucose, liver and hormone profiles.
Within the cohort, transgender males were prescribed an average testosterone dose of 217 mg per month for an average treatment duration of 11.2 months. Six participants had undergone chest masculinizing surgery, and all transgender males previously had menarche. Transgender females were prescribed an average estradiol dose of 1.5 mg per day with an average treatment duration of 12.3 months, with seven prescribed spironolactone for androgen blockade.
Researchers found that total body fat was lower among transgender males vs. cisgender females (mean, 29% vs. 33%; P = .002) and higher vs. cisgender males (mean, 28% vs. 24%; P = .047). Transgender males had higher lean mass vs. cisgender females (mean, 68% vs. 64%; P =.002) and lower lean mass vs. cisgender males (69% vs. 73%; P = .029).
Transgender females had a lower body fat percentage vs. cisgender females (mean, 31% vs. 35%; P = .033) and higher body fat percentage vs. cisgender males (mean, 28% vs. 20%; P = .001). Transgender females also had a higher lean mass vs. cisgender females (mean, 66% vs. 62%; P = .032) and lower lean mass vs. cisgender males (mean, 69% vs. 77%; P = .001).
“The percentage lean and percentage fat mass were remarkably similar for the transgender females and transgender males; these groups were not matched on age or BMI or compared to one another,” the researchers wrote.
There were no between-group differences for insulin sensitivity measurements among transgender males vs. controls; however, researchers found that transgender females were more insulin resistant vs. cisgender males (mean, 0.078 vs. 0.142; P = .011).
The researchers noted that the differences in body composition observed among transgender females may be explained by a male pattern of lean mass accrual during puberty, followed by a gain in percent fat and concomitant rise in leptin due to estradiol treatment, whereas body composition observed among transgender males may be explained by pubertal fat accrual followed by gains in lean mass with testosterone.
“More research is needed to understand the changes in cardiometabolic health on gender-affirming hormone therapy and to improve care for transgender individuals,” Nokoff said. – by Regina Schaffer
For more information:
Natalie Nokoff, MD, can be reached at the SOAR Clinic, Children’s Hospital Colorado, 13123 E. 16th Ave., Box B265, Aurora, CO 80045; email: natalie.nokoff@childrenscolorado.org.
Disclosure: Nokoff reports she previously consulted for Antares Pharma.
Perspective
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Courtney Finlayson, MD
This is an important pilot study with potential for future research to inform care of transgender individuals as well as to inform knowledge about the role of reproductive hormones in metabolism and disease. Currently, the body of knowledge about effects of gender-affirming hormones is hampered by lack of long-term studies evaluating direct and indirect effects of such hormone treatment. It is important that research evaluate long-term effects on common disease processes rather than simply direct effects of the hormone treatment. Preliminary evidence suggests a slightly higher rate of type 1 diabetes in transgender individuals, and if this proves to be true, the influence of hormone treatment on insulin resistance may become increasingly important in treating comorbid processes. This is a pilot study and by its nature includes a relatively small sample size and duration of treatment. It will be interesting to see if, in a larger population and longer study duration, these findings are consistent or if, for example, body fat and lean body mass more closely approach those seen in the affirmed gender. Future findings may also provide models and insight into other conditions, such as developmental origins and outcomes of hyperandrogenism in polycystic ovarian syndrome.
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