Lei Yu, Wiik Anna, Connelly Margery A, Lindberg Linnea, Andersson Daniel P, Arver Stefan, Gustafsson Thomas, Tietge Uwe J F
Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, S-141 83 Stockholm, Sweden.
Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, and Unit of Clinical Physiology, Karolinska University Hospital, S-141 83 Stockholm, Sweden.
J Clin Endocrinol Metab. 2025 Jun 17;110(7):e2273-e2284. doi: 10.1210/clinem/dgae745.
While transgender individuals represent a substantial group seeking medical care, the differential effect of sex on cardiometabolic risk metrics is incompletely understood.
The present study aimed to characterize the effect of sex hormones and chromosomes on a contemporary panel of cardiometabolic risk biomarkers and functional cardiovascular measurements.
A total of 17 transgender men and 17 transgender women were studied at baseline (T0), 4 weeks (hormonal castration, T1), and 11 months following gender-affirming hormone treatment (T12). We analyzed carotid intima-media thickness and arterial stiffness, lipoproteins, and other metabolites comprehensively by nuclear magnetic resonance spectroscopy and high-density lipoprotein-mediated cholesterol efflux capacity (CEC) from macrophages. T0 to T12 comparisons informed the effect of sex hormones, comparisons of genetic XX and XY individuals at T1 the effect of sex chromosomes.
Vascular function was comparable at T12 and T0; systolic blood pressure increased in transgender men (P = .002). Transgender men developed a proatherogenic lipoprotein profile; estrogen treatment in transgender women tended to result in improvements. Several metabolites indicating increased diabetes risk including plasma glucose were changed in transgender men (P = .025), with opposite changes in transgender women (P = .002). Interestingly, at T1 apparent diabetes risk was lower in XX compared with XY individuals (P = .002). CEC decreased in transgender women (P < .01), while remaining unchanged in transgender men. However, in both groups the strong positive association of apolipoprotein A-1 with cholesterol efflux observed at T0 was lost at T12.
The results are consistent with increased cardiometabolic risk in transgender men, while transgender women show beneficial changes early during gender-affirming hormone therapy. Sex chromosomes have fewer intrinsic effects. XY individuals and transgender men display an increased apparent diabetes risk. Further research on cardiometabolic risk is needed for transgender individuals.
虽然跨性别者是寻求医疗护理的一个重要群体，但性别对心脏代谢风险指标的差异影响尚未完全明确。
本研究旨在描述性激素和染色体对一组当代心脏代谢风险生物标志物及心血管功能测量指标的影响。
对17名跨性别男性和17名跨性别女性在基线期（T0）、4周时（激素去势，T1）以及性别确认激素治疗11个月后（T12）进行研究。我们通过核磁共振波谱法全面分析了颈动脉内膜中层厚度和动脉僵硬度、脂蛋白及其他代谢物，并分析了巨噬细胞中高密度脂蛋白介导的胆固醇流出能力（CEC）。T0至T12的比较揭示了性激素的影响，T1时XX和XY个体的比较揭示了性染色体的影响。
T12时的血管功能与T0时相当；跨性别男性的收缩压升高（P = 0.002）。跨性别男性出现了促动脉粥样硬化的脂蛋白谱；跨性别女性接受雌激素治疗往往会有改善。跨性别男性中几种提示糖尿病风险增加的代谢物（包括血糖）发生了变化（P = 0.025），而跨性别女性则出现相反变化（P = 0.002）。有趣的是，在T1时，XX个体的明显糖尿病风险低于XY个体（P = 0.002）。跨性别女性的CEC降低（P < 0.01），而跨性别男性则保持不变。然而，在两组中，T0时观察到的载脂蛋白A-1与胆固醇流出的强正相关在T12时消失。
结果表明跨性别男性的心脏代谢风险增加，而跨性别女性在性别确认激素治疗早期显示出有益变化。性染色体的内在影响较小。XY个体和跨性别男性的明显糖尿病风险增加。跨性别者的心脏代谢风险需要进一步研究。
