Gender-affirming hormone therapy (GAHT) is common among transgender and gender-diverse adults. Transmasculine adults typically receive testosterone and transfeminine adults generally receive a combination of estrogen and an antiandrogen if they have not undergone an orchiectomy. GAHT is medically-necessary treatment taken to align physical characteristics with gender identity and to improve quality of life and psychological well-being1,2. Nonetheless, GAHT has important metabolic effects that likely alter cardiovascular risk.

The prevalence of several cardiovascular conditions may be higher in transgender adults than cisgender adults according to several large epidemiological studies3,4. For example, data from a multivariable adjusted model from the Behavioral Risk Factor Surveillance System found that trans men were 4.9 times as likely to report having had a myocardial infarction as compared to cisgender women4. Intramuscular testosterone therapy has also been found to increase systolic blood pressure in trans men5,6. Given that lipid concentrations play an important role in the development of atherosclerotic cardiovascular disease, it is important to understand how GAHT may modify cardiovascular risk.

A systematic review and meta-analysis of studies published up until 2015 found low-quality evidence that GAHT may affect serum lipid concentrations7. Specifically, transmasculine adults had an increase in low-density lipoprotein cholesterol (LDL-C) (+18 mg/dL) and triglycerides (TG) (+21 mg/dL) and a decrease in high-density lipoprotein cholesterol (HDL-C) (-9 mg/dL)7. Transfeminine adults only had an increase in TG (+32 mg/dL) with no changes to total cholesterol (TC), LDL-C or HDL-C7. Since this meta-analysis, the European Network for the Investigation of Gender Incongruence (ENIGI) published the largest study to date on the topic in 2019 using data from patients in Belgium and the Netherlands8. This study included 188 trans men on various formulations of testosterone (intramuscular undecanoate, intramuscular esters and topical gel) and 242 trans women on various formulations of estradiol (oral or transdermal) and cyproterone acetate. In contrast to the meta-analysis, this study revealed changes to all lipid parameters with the use of GAHT. Trans men on testosterone therapy for one year, regardless of testosterone formulation, had a 4% increase in TC, 13% increase in LDL-C, 37% increase in TG and 11% decrease in HDL-C8. Likewise, trans women had a 10% decrease in TC, 6% decrease in LDL-C, 10% decrease in TG and 9% decrease in HDL-C8.

Given the paucity and inconsistent findings on the effects of GAHT on lipid parameters from studies with at least 50 subjects, we aimed to conduct one of the largest and longest observational studies using a racially and ethnically diverse population of gender diverse individuals in the United States. We also sought to establish prevalence rates of moderate hypertriglyceridemia, low levels of HDL-C and hypercholesterolemia in this population.