Cardiac Biomarkers Reflect Sex Hormones in Transgender People

Just as in cisgender individuals, transgender people show variations in cardiac biomarkers that appear related to sex hormones, according to a new cross-sectional study.

Trans men who were taking testosterone saw increased high-sensitivity cardiac troponin (hs-cTn) levels in comparison to trans women who were taking estradiol. For N-terminal pro-brain natriuretic peptide (NT-proBNP), levels were decreased for trans men as compared with trans women. Moreover, the study’s authors say, the extent of these differences matches what’s observed between cis men and cis women.

“Sex hormones, rather than sex assigned at birth, may be a stronger driver of the observed concentration differences between healthy men and women for biomarkers of cardiac disease,” Dina N. Greene, PhD (University of Washington, Seattle), and colleagues note in their paper, published online yesterday in JAMA Cardiology.

Speaking with TCTMD, Greene said she was struck by the clear patterns shown by their results. “Data does not usually look this good,” she noted, adding that it also came as a surprise to see such consistency among the assays they used. “The fact that we saw the exact same trend across the three [troponin] assays was really powerful.”

This work adds a new layer of representation to the literature by focusing on transgender individuals, Greene noted. “For me, that’s the biggest thing: how do we normalize gender expansiveness?”

What their study suggests is that “there is structural remodeling that happens in the heart when people take testosterone or estradiol that we don’t totally understand. Sex hormones influence cardiac physiology,” Greene explained. However, she stressed that their study should be considered basic research and cautioned against applying their findings in practice.

Few data exist on cardiovascular disease in transgender and gender-diverse adults, but there’s growing recognition that the poorer health seen in this population, as compared to cisgender adults, isn’t fully explained by traditional risk factors. As noted by a 2021 American Heart Association scientific statement, psychosocial stressors such as discrimination and lack of access to healthcare are contributing to their excess CV morbidity and mortality.

There is structural remodeling that happens in the heart when people take testosterone or estradiol that we don’t totally understand. Dina N. Greene

For their cross-sectional study, Greene and colleagues enrolled 79 trans men who had been prescribed testosterone (mean age 28.8 years) and 93 trans women who had been prescribed estradiol (mean age 35.1 years) for at least 12 months. The mean duration of hormone therapy was 4.8 and 3.5 years, respectively.

Cardiac biomarkers were evaluated by the ARCHITECT STAT (Abbott Diagnostics) and ACCESS (Beckman Coulter) high-sensitivity troponin I assays, the Elecsys Troponin T Gen5 STAT assay (Roche Diagnostic), and the Elecsys ProBNP II assay (Roche Diagnostics).

They found that hs-cTnI levels ascertained by the ARCHITECT STAT were higher among trans men as compared with trans women, with similar patterns detected on the other two troponin assays. With NT-proBNP, values were higher for trans women than for trans men.

Cardiac Biomarkers Among Healthy People: Median (IQR)

“The observed differences in hs-cTn concentration are likely physiological and not pathological, as concentrations of hs-cTn between healthy cisgender people are also apparent and, as population-based observations, are not thought to portend adverse events,” the study authors note, adding, “Ultimately, the psychosocial benefits of gender-affirming hormones are substantial, and informed consent is likely the ideal method to balance the undetermined risks.”

Greene said her interest in this topic emerged from her earlier work on sex-related differences in cardiac biomarkers among cisgender people and gender-related aspects of cardiovascular medicine.

For instance, female patients tend to have a lower 99th percentile upper reference limit for hs-cTn than do male patients, Greene pointed out. Additionally, prior social-science research performed in cisgender individuals has shown that “different expressions of gender can influence the care you receive,” she noted. “The more masculine you are, the more likely you are to be taken seriously for signs and symptoms of acute myocardial infarction, and the more feminine you are, the less likely you are.”

With more research done in more people, a better understanding of biomarker levels—cardiac and otherwise—in transgender patients could be used to improve diagnostic tools, Greene noted. Future studies should also include baseline biomarker assessment and cardiac imaging to capture what happens when starting hormone therapy.

“Gender-affirming therapy is essential to the overall well-being and health of transgender persons, and more research is needed to quantify any potential adverse cardiac consequences and develop better strategies to optimize cardiac health in this population,” the paper concludes.