Cardiometabolic disease burden in transgender women (TW) is affected by feminizing hormonal therapies (FHT), HIV and antiretroviral therapy (ART), but little data are available with contemporary FHT regimens and well-matched controls. We assessed relationships between sex hormone concentrations, body composition and inflammatory biomarkers among TW and matched cisgender men (CM).
Adult TW on FHT (n=33) were recruited from Houston, TX and Baltimore, MD for a cross-sectional study (2018-2020). CM (n=60) from the Multicenter AIDS Cohort Study Cardiovascular 2 or 3 sub-studies were matched (2:1) to TW on HIV serostatus, age within 5 years, race/ethnicity, BMI category and ART type. All HIV+ persons had HIV-1 RNA <50 copies/ml on ART. Body composition was measured by non-contrast computed tomography. Sex hormones and inflammatory biomarker concentrations were measured centrally.
TW were 71% non-white, 76% HIV+ (72% INSTI-based ART use) and had median age 51 years and BMI 29 kg/m2. Only 31% of TW had testosterone suppression, with median total testosterone 325 vs 441 ng/dl for CM and similar free testosterone (3%). Median estradiol for TW was 85 vs 23 pg/ml for CM. TW had greater subcutaneous thigh muscle fat (16 vs 7 cm2, p<0.001) and tended to have greater subcutaneous abdominal fat (345 vs 279 cm2, p=0.09). TW had significantly (p<0.05) higher endothelin (ET)-1 (3.1 vs 1.5 pg/mL), EN-RAGE (23.0 vs 9.1 pg/ml) and adiponectin (5.6 vs 3.9 ?g/ml) concentrations vs CM. Higher estradiol (r=0.374, p<0.001) and lower total testosterone (r=-0.30, p=0.006) concentrations correlated with greater thigh muscle fat; lower total testosterone concentrations also correlated with greater abdominal subcutaneous (r=-0.29, p=0.008) and visceral fat (r=-0.22, p=0.04) area. Higher estradiol concentrations correlated with higher adiponectin (r=0.24, p= 0.03), ET-1 (r=0.22, p= 0.046), and EN-RAGE (r=0.40, p<0.001) concentrations.
In this group of older TW on FHT, higher estradiol and lower total testosterone concentrations were associated with worse body composition and mixed effects on select cardiometabolic biomarkers. Specifically, greater visceral fat and fatty muscle infiltration and higher endothelin-1 and EN-RAGE concentrations have been associated with increased cardiovascular risk in the general population, though higher adiponectin is generally thought to be beneficial. More nuanced understanding of the relationships between FHT and cardiometabolic risk in TW is needed.