Commentary based on Ong C, Monita M, Liu M. Gender-affirming hormone therapy and cardiovascular health in transgender adults. Climacteric 2024;27:227-35.¹

Current cardiovascular (CV) guidelines do not incorporate gender identity and hormone status into risk stratification and clinical decision-making. Clinical understanding of gender-affirming hormone therapy (GAHT) on CV health has been limited by a lack of high-quality research. The following commentary is based on current literature on the cardiometabolic impact of GAHT and discusses clinical considerations for CV risk in transgender patients.

1. Most transgender people rely on GAHT to mitigate gender dysphoria. Given the limited data on the effects of GAHT on CV health, changes to or cessation of GAHT for poorly represented CV disease risk mitigation can lead to decreased gender congruence, thereby reducing quality of life.
2. Several factors related to GAHT may influence CV health, including variations in personalized hormone regimen, administrative route, duration of treatment, age of onset of medication use, and age-adjusted dosing of hormone therapy for transgender persons who are older.
3. The results of a 5-decade–long analysis of Dutch transgender men and women, the largest observational study to date, have shown: 1) an elevated CV death rate in this group compared with that of cisgender adults; and 2) myocardial infarction (MI) was the most common CV cause of death in this group. However, no current study data demonstrate a clear link between GAHT and CV outcomes.
4. There are nine ongoing trials evaluating the CV effects of GAHT, including one randomized controlled trial in the United States to assess the impact of gender-affirming estradiol therapy on insulin resistance, lipid profile, and coagulation factors.
5. Observational study data have shown that, for bioidentical estradiol, the route of administration is important. Transdermal estradiol, compared with oral estradiol, has shown to be associated with lower risks of MI, stroke, and venous thromboembolism (VTE).
6. For those receiving progesterone in their feminizing hormone regimen, recent study data have shown that bioidentical progesterone, compared with synthetic progestins, is associated with higher high-density lipoprotein (HDL) levels and lower risk of VTE.
7. Data from a few prospective and retrospective studies have shown that testosterone is associated with an increase in low-density lipoprotein levels and decrease in HDL levels; however, HDL level changes might stabilize over time, as seen in the results of one longitudinal study.
8. An increase of systolic blood pressure (BP) in those taking testosterone led to a higher observed outcome of stage 1 hypertension. There are inconsistencies in the reported impact of estrogen on BP, as study data have shown both increases and decreases in BP with estrogen.
9. Body fat percentages tend to increase with the initiation of feminizing hormones and to decrease with testosterone use. However, as the transgender community endures socioeconomic obstacles related to food insecurity, poverty, and psychosocial distress, this may modify the effects of GAHT on obesity.
10. Antitransgender laws can further elevate CV risk in transgender people by exacerbating societal stressors, worsening mental health, and contributing to unhealthy coping mechanisms such as tobacco, alcohol, and substance use.
11. Transgender patients have been under-represented in clinical research, health care surveys, and other data-collecting opportunities, in part because of the medical community's lack of familiarity with transgender identity and gender-affirming care.
12. High-quality studies that evaluate the impact of GAHT on transgender people's CV health are needed to inform clinical decisions with robust evidence-based data.

References

1. Ong C, Monita M, Liu M. Gender-affirming hormone therapy and cardiovascular health in transgender adults. Climacteric 2024;27:227-35.