Sex steroid treatment changes HDL cholesterol levels in transgender youth

illustration of person wearing trans shirt with HDL above and below
A new study finds that HDL levels change in trans youth after taking sex steroids as part of gender-affirming treatment. (Image: AdobeStock/Illustration: Sebastian Stankiewicz, Boston Children's)

In an important study in transgender youth, researchers at Boston Children’s Hospital and colleagues have discovered that HDL cholesterol levels change within six months after starting gender-affirming medical treatment. HDL levels dropped an average 7 points in transmasculine patients and they rose by about 11 points in transfeminine youth. The HDL shifts do not indicate that trans youth have any change to their cardiovascular risk profile compared with cisgender youth of the same age.

Kate Millington photo
Kate Millington

The shifts appear to be due to the sex steroids, testosterone and estradiol, that some trans individuals take as part of treatment to align their body with their gender identity.

“Our study found that trans youth essentially swap their HDL profile from the gender they were assigned at birth to their trans identity,” says study co-leader Kate Millington, MD, of the Department of Endocrinology and Gender Multispecialty Service at Boston Children’s. The team’s discoveries are published in a paper in JAMA Pediatrics.

HDL levels switched within six months of treatment

The study included approximately 300 children and adolescents between ages 13 and 20 who were receiving sex steroid treatment as part of their gender-affirming care. As the team had already noted in an earlier study, those transitioning to male already had slightly lower HDL levels (50.6 mg/dL) compared with an average HDL level of 53.3 mg/dL in age-matched cisgender males who served as the control group. Otherwise, there were no identified differences between the trans and cisgender youth in terms of body mass index, proportion of patients overweight and obese, blood pressure, or other laboratory variables.

Yee Ming Chan headshot
Yee-Ming Chan

“Within six months of beginning sex steroid treatment, HDL levels in both transgender males and females changed to those of their identified gender,” says co-author Yee-Ming Chan, MD, PhD, pediatric endocrinologist and director of the Behavioral Health, Endocrinology, Urology (BE-U) Program at Boston Children’s.

Notably, in transgender males, the HDL levels dropped to a point slightly lower than typically found in cisgender males. This decline was not unexpected, as several studies in trans male adults have previously shown that HDL drops after testosterone treatment. The team does not know why HDL declined below the typical range, but plans on searching for clues.

Increase in HDL in transfeminine patients

The study also revealed for the first time that estradiol increases HDL in transfeminine youth, in contrast with studies in trans female adults where this has not been seen consistently.

“It really makes us wonder if there is something about adolescence that is especially important for these effects, and that if you wait too long, maybe you lose this window of opportunity to get the improvements in HDL that we don’t really see in data from adults,” says Millington.

The long-term view of transgender health

This study used data from the Trans Youth Care (TYC) study begun in 2015, a long-term multi-center national study of gender-affirming medical care of transgender children and adolescents in the United States.

“It’s one of the biggest studies of transgender youth in the United States, including about 500 participants,” says Chan, who leads the Boston Children’s branch of the TYC study. The team collects both psychosocial outcomes and extracts medical data from the medical record to look at physical outcomes as well and consequences of starting gender-affirming treatments. “It’s a really great opportunity not just for us to better understand trans health but to get a lot of insight into human health in general.”

Transmasculine youth not necessarily at higher cardiovascular risk

It is well known that lower HDL levels are associated with a higher risk for cardiovascular disease and that higher levels are associated with lower risk.

“But just because the trans male youth had lower HDL after treatment, it does not mean they are at a particularly higher risk for cardiovascular problems,” says Millington. “Instead, it means that they have the expected cardiovascular risk of someone of their identified gender, in this case the same as the average cisgender male of the same age,” she adds.

However, obesity did appear to have a negative influence on HDL in transmasculine and transfeminine youth. The team observed that the HDL drop in trans male youth was larger in those defined clinically as obese, with a BMI greater than the 95th percentile on pediatric growth charts. And, HDL levels did not increase in transfeminine youth with obesity.

The takeaway: physicians treating trans patients should watch laboratory values just as they would with any patients who have a high BMI or other health risk factors that increase cardiovascular disease risk, like smoking or poor dietary habits.

Learn more about the Gender Multispecialty Service or refer a patient.

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