Gender-affirming HT influences HDL cholesterol levels in adolescents
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Gender-affirming hormone therapy causes changes in HDL cholesterol levels for transgender adolescents, and obesity can modify these associations, according to a research letter published in JAMA Pediatrics.
“Our research provides additional information on the role of sex steroids in cholesterol metabolism,” Kate Millington, MD, attending physician in the division of endocrinology at Boston Children’s Hospital, told Healio. “It provides clinicians with additional information regarding the impact of testosterone and estradiol on cholesterol, which has implications for doctors caring for both transgender and cisgender youth.”
Millington and colleagues analyzed data from 269 adolescents (69% designated female at birth) with no prior gonadotropin-releasing hormone use before starting gender-affirming HT. Participants were recruited at four U.S. study sites between July 2016 and September 2018. Laboratory and anthropometric data were collected at baseline and at 6 and 12 months after HT was initiated.
In 83 transfeminine participants designated male at birth, HDL cholesterol increased by a mean 11.2 mg/dL after 6 months of estradiol therapy (95% CI, 8.6-13.8; P < .001), putting them within the normal range for female adolescents. Transmasculine participants designated female at birth had a mean HDL cholesterol decrease of 7.2 mg/dL after 6 months of testosterone therapy (95% CI, 5.3-9.1; P < .001), placing their level similar to that of the designated male at birth transfeminine cohort at baseline.
Among transfeminine participants, those with obesity had lower HDL cholesterol levels at baseline compared with those without obesity (36 mg/dL vs. 46.1 mg/dL; P = .01) and had no increase in HDL cholesterol levels at follow-up. In transmasculine cohort, baseline HDL cholesterol was not different in those with obesity and those without. However, participants with obesity had a larger decrease with testosterone therapy compared with those without obesity (–12.1 mg/dL vs. –5.5 mg/dL; P = .004).
“To our knowledge, this is the first report of the modifying association of obesity with changes in HDL cholesterol levels with gender-affirming HT, exacerbating the decrease in HDL cholesterol levels with testosterone and blunting the benefit of estradiol treatment,” the researchers wrote. “Our results provide direct evidence for the hypothesis that changes in HDL cholesterol levels during puberty and the differences in HDL cholesterol levels between men and women are caused primarily by differences in sex steroids and that sex steroids work synergistically with other risk factors such as obesity.”
Millington said the findings are the first step into examining health outcomes of transgender adolescents receiving gender-affirming HT.
“Many additional studies are planned to further examine cholesterol metabolism in transgender youth, to look at additional health behaviors in this population that may improve cardiovascular health and looking at the outcomes of gender-affirming care in general,” Millington said.
For more information:
Kate Millington, MD, can be reached at kate.millington@childrens.harvard.edu.
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