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Many transgender youth will likely face a higher risk of poor cardiometabolic outcomes, according to new research.

An analysis of over 4,000 American youth diagnosed with gender dysphoria found these patients had a nearly two times higher chance of developing metabolic syndrome compared with youth without gender dysphoria (OR 1.9, 95% CI 1.2-3.0, P=0.0086), reported Anna Valentine, MD, of the University of Colorado Anschutz Medical Campus in Aurora.

In her presentation at the Endocrine Society's virtual ENDO 2021 meeting, Valentine explained that these youth -- including both those assigned male at birth and female at birth -- also had a significantly higher odds of developing dyslipidemia compared with cisgender youth (OR 1.6. 95% CI 1.3-1.8, P<0.0001).

For only transgender youth assigned female at birth, the researchers found that these individuals had a significantly higher odds of developing overweight or obesity (OR 1.7, 95% CI 1.5-1.9, P<0.0001). They also had a nearly two times higher chance of being diagnosed with polycystic ovary syndrome (OR 1.9, 95% CI 1.3-2.8, P=0.0006) compared with cisgender female youth.

On the other hand, transyouth did not have an excess risk of hypertension, dysglycemia, or liver dysfunction.

A number of different mechanisms could underlie these findings, Valentine explained during a press conference. "We know that some youth with gender dysphoria have higher rates of overweight and obesity, and that having overweight and obesity itself increases your risk of having other diagnoses." It is also known that "youth with gender dysphoria have higher rates of mental health comorbidities ... as well as getting less physical activity," she said.

"And they also may be taking medication that could all influence their cardiometabolic health," she added.

Although less research has been done in pediatric patients, Valentine also referenced adult data showing that adult transwomen on estradiol are more likely to have increased triglycerides and a higher rate of stroke, blood clots, and myocardial infarction (MI).

Additionally, adult transmen on testosterone have been shown to have a higher risk of increased triglycerides, low-density lipoprotein cholesterol, and body mass index (BMI), as well as lower high-density lipoprotein cholesterol, and an increased risk of MI.

The retrospective cohort study looked at data from the PEDSnet health learning system, which included electronic health record data from six large pediatric centers, including from Children's Hospital of Philadelphia, Nationwide, Nemours, St. Louis, Colorado, and Seattle.

A total of 4,174 pediatric patients with a diagnosis of gender dysphoria were included, who were then compared with 16,651 controls. All youth with gender dysphoria were matched with four controls based on year of birth, age at last visit, site, race, ethnicity, insurance status, and duration in the database. The average age of 16 at the last clinical visit and the majority of transgender youth were assigned female at birth (66%), were white (73%), and had private insurance (61%).

Because inclusion criteria for transgender youth were based only on a diagnosis of gender dysphoria, there was a lack of data on exactly who was receiving hormonal therapy, Valentine noted.

She told MedPage Today that this will be the focus of the team's next study, which will look specifically at cardiometabolic outcomes in transgender youth receiving gender-affirming hormone therapy.

"We do know that in the adult data, that there is some association with estradiol use and testosterone use with differences in cholesterol parameters, but this is still an emerging field in pediatrics," Valentine explained. "We have some small single-center studies that sometimes say 'yes, with hormones we see an increase in BMI,' but other studies say 'this section looks very stable on this hormone.'"

"The fact that we have such a large cohort in this multicenter analysis for our next steps, I think it will be really interesting to look at that," she added.

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