Impact of Estradiol-Dominant GAHT on Visceral Fat and Hepatic Lipids in US Cohort
Overview
In a 12-month prospective study of 26 transgender women and nonbinary individuals initiating estradiol-based gender-affirming hormone therapy (GAHT), visceral adipose tissue (VAT) and insulin sensitivity remained stable. Notably, intrahepatic triglyceride content decreased, while lean body mass declined and systemic triglycerides increased.
Background
Transgender women and gender-diverse individuals often undergo long-term GAHT consisting of 17β-estradiol combined with anti-androgen therapy to affirm gender identity. Despite its widespread use, the metabolic effects of this therapy remain incompletely understood, particularly regarding cardiovascular and metabolic disease risks. Prior studies indicate persistent cardiometabolic risk despite GAHT, underscoring the need to characterize changes in body composition, hepatic fat, and insulin sensitivity. This study aimed to prospectively evaluate these parameters over 12 months in a US cohort without preexisting cardiovascular disease or diabetes.
Data Highlights
Parameter
Change After 12 Months
Statistical Significance
Visceral Adipose Tissue (VAT) Mass and Volume
No significant change
Not significant
Intrahepatic Triglyceride Content (hTG)
Median decrease of −0.2% (IQR −1.3 to 0.1)
P = .03
Total Lean Body Mass
Mean decrease of −0.31 ± 0.38 kg/m²
P = .0003
Appendicular Lean Body Mass/Height²
Decreased (unfavorable)
Significant
Bone Density (Lumbar, Total Hip, Femoral)
Increased
Significant
Insulin Sensitivity
No significant change
Not significant
Systemic Triglycerides
Increased
Significant
HDL and LDL Cholesterol
No significant change
Not significant
Key Findings
Visceral adipose tissue mass and volume remained stable after 12 months of estradiol-dominant GAHT.
Total and appendicular lean body mass decreased, suggesting a risk for sarcopenia.
Bone density at lumbar spine, total hip, and femoral sites increased over the study period.
Insulin sensitivity did not change significantly despite hormonal therapy.
Systemic triglyceride levels increased, while HDL and LDL cholesterol levels remained unchanged.
Clinical Implications
Clinicians should be aware that estradiol-based GAHT may reduce hepatic fat but also decrease lean body mass, potentially increasing sarcopenia risk. Monitoring body composition and implementing strategies to preserve muscle mass may be warranted. Stable visceral fat and insulin sensitivity suggest no immediate worsening of these metabolic parameters, but lipid profile changes require attention.
Conclusion
Estradiol-dominant GAHT in transgender women and nonbinary individuals leads to favorable reductions in hepatic fat and increased bone density but is associated with decreased lean mass and increased triglycerides. These findings highlight the importance of comprehensive metabolic monitoring during GAHT.
References
Study Authors/US Cohort Study 2024 -- Impact of 17-beta Estradiol-Dominant Gender-Affirming Hormone Therapy on Visceral Fat and Hepatic Lipids
by Ria Talathi, Vencel Juhasz, Matilda Delgado, Thiago Quinaglia, Azin Ghamari, Melissa Wang, Iad Alhallak, Sarah Stinebaugh, Sophia Campbell, Sara L Stockman, Mustafa A Ozturk, Sadia M Ahmadi, Sara E Looby, Hang Lee, Tonia C Poteat, Lidia S Szczepaniak, Markella V Zanni, Tomas G Neilan, Mabel Toribio
