Transmasculine Hormone Therapy Could Carry Greater Cardiovascular Risk than Transfeminizing Therapy

An analysis of nearly 3 dozen studies of patients receiving gender-affirming hormone therapy (GAHT) is offering an overview of the impact this has on cholesterol and other blood lipids.

With data from 35 studies assessing the effects of initiating transfeminizing or transmasculinizing GAHT, results suggest transmasculine patients may require more attentive monitoring for changes in lipid profile, with significant changes observed for LDL-C and other lipids, while these changes were not apparent among transfeminine patients.¹

“We observed an overall worsening of blood lipid profiles following the initiation of masculinizing GAHT, with changes especially evident 5 years since the start of testosterone therapy. By contrast, studies of [transfeminine] populations receiving estrogen-containing GAHT on balance demonstrated relatively stable lipid profiles,” wrote investigators.¹

The prevalence of GAHT use has increased exponentially since the turn of the century, with a 2023 report suggesting the proportion of adults with a transgender-related diagnosis code increased by 30.8% each year from 2014 to 2021, with the proportion of these patients prescribed GAHT increasing from 30.5% in 2014 to 43.4% in 2021. Considering the risk of cardiovascular disease associated with use of hormone in certain patient populations, investigators sought to better understand how initiation of feminizing or masculinizing GAHT might influence lipid profile among patients receiving GAHT.²

A team of 5 investigators, led by Michael Goodman, MD, MPH, of the Department of Epidemiology at the Rollins School of Public Health at Emory University, designed the current study as a systematic review and meta-analysis of relevant articles on the subjected published from 1990 through February 27, 2024. Investigators leveraged the Ovid MEDLINE, Embase, SCOPUS, CINAHL, and Web of Science database for the study and included both observational studies and randomized trials, with inclusion criteria requiring studies to reported laboratory parameters of interest at baseline and at specified intervals of 3, 6, 9, 12, 18, 24, 36, or 60 months following GAHT initiation.¹

Outcomes of interest for the study were changes from baseline to the aforementioned time intervals for LDL-C, HDL-C, triglycerides, and total cholesterol. Investigators noted statistical heterogeneity was assessed using Cochran’s Q test and expressed as the I2 statistic, which was interpreted using cut-offs of 25%, 50%, and 75% for low, moderate, and substantial heterogeneity, respectively.¹

A total of 1943 unique abstract titles underwent screening. In total, 36 studies were included in the meta-analysis. Among these, 17 focused on Transmasculine populations only, 8 focused on transfeminine populations only, and 11 included both Transmasculine and transfeminine populations. Investigators noted 22 of the 36 studies had a maximum follow-up of 12 or 24 months, with 5 studies following patients for 60 months and 1 study following patients for 72 months.¹

Assessment of studies related to masculinizing GAHT suggested initiation of therapy was associated with significant changes in serum lipids from baseline up through the 60-month timepoint, with meta-difference of means estimates (MDM) of 26.2mg/dL (95% Confidence Interval [CI] 23.3 to 29.0; P <.001; I2 = 0%) for LDL-C, 26.1mg/dL (95% CI, 22.8 to 29.4; P <.001; I2 = 0%) for total cholesterol, 30.7mg/dL (95% CI, 6.9 to 54.6; P = .03; I2 = 35%) for triglycerides, and –9.4mg/dL (95% CI, –12.1 to –6.7; P <.001; I2 = 0%) for HDL-C. Assessment of studies related to feminizing GAHT suggested there were no significant changes in HDL-C (MDM, 5.3; 95% CI, −1.7 to 12.4; P = .11; I2 = 54%) or triglycerides (MDM, 4.7; 95% CI, −21.3 to 30.6; P = .64; I2 = 52%) observed and the results for LDL-C (MDM, 6.6; 95% CI, 2.4 to 10.8; P = .01; I2 = 0%) and total cholesterol (MDM, 13.8; 95% CI, 2.6 to 25.0; P = .02; I2 = 5%) were inconsistent.¹

Investigators noted multiple limitations within their study to consider when interpreting findings. These included inability to complete all steps in duplicate and the limitations and knowledge gaps within existing literature.¹

“These results appear somewhat reassuring for [transfeminine] individuals on GAHT," investigators wrote.¹ "The results also suggest that [transmasculine] patients receiving testosterone may benefit from closer monitoring of lipid profiles or lifestyle interventions; however, the direct impact of masculinizing GAHT on cardiovascular disease risk is beyond the scope of the present review.”

References:

1. _{^{Gosiker B, Moutchia J, Nguyen N, Getahun D, Goodman M. Changes in Blood Lipids Following Initiation of Gender Affirming Hormone Therapy: A Systematic Review and Meta-Analysis. J Clin Transl Endocrinol. 2024;36:100349. Published 2024 Apr 30. doi:10.1016/j.jcte.2024.100349}}
2. _{^{Huang YA, Radix A, Zhu W, Kimball AA, Olansky EJ, Hoover KW. HIV Testing and Preexposure Prophylaxis Prescriptions Among U.S. Commercially Insured Transgender Men and Women, 2014 to 2021. Ann Intern Med. 2024;177(1):12-17. doi:10.7326/M23-2073}}